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Lymphatic system

Non-Hodgkin lymphoma (DLBCL and follicular)

How rituximab-based chemoimmunotherapy, CAR T cells and bispecific antibodies changed care for diffuse large B-cell and follicular lymphoma.

Diffuse large B-cell lymphoma only · 5-year relative survival · United States, SEER 8 registries

36.05%→70.78%

1975 (observed value; first year in the table) to 2018 (observed value; last observed year in the table). Read these with the caveats under “Then and now”.Source

26 milestones, by decade

  • In SEER 8 data on the Cancer Stat Facts pages, observed five-year relative survival was 36.05% for diffuse large B-cell lymphoma and 66.05% for follicular lymphoma in the first year of each table (1975), and 70.78% and 92.82% in the last observed year (2018). Over 1992-2023 the age-adjusted death rate in SEER 8 incidence-based mortality went from 2.80 to 1.53 per 100,000 for DLBCL and from 1.59 to 0.34 for follicular lymphoma. The pages do not label the year as year of diagnosis and do not say how much of the change reflects treatment, classification, diagnostic practice or case mix; single-year values vary (follicular lymphoma was 55.29% in 1977 and 93.78% in 2014).
  • Five accelerated approvals for relapsed, or relapsed or refractory, follicular lymphoma (the list words the idelalisib and copanlisib indications as relapsed) granted between 2014 and 2021, to idelalisib (23 July 2014), copanlisib (14 September 2017), duvelisib (24 September 2018), tazemetostat (18 June 2020) and umbralisib (5 February 2021), all appear on the FDA's list of withdrawn cancer accelerated approvals, with withdrawal dates from 17 December 2021 to 22 June 2026. The list gives no reasons and defines the withdrawal date as the Federal Register effective date or the date the product label was updated, whichever came first. The accelerated approvals of idelalisib and umbralisib also covered other lymphomas. The same list shows the accelerated approval of selinexor for relapsed or refractory DLBCL (22 June 2020) withdrawn on 30 April 2026.
  • In a randomised comparison reported in 1993 by the Southwest Oncology Group and the Eastern Cooperative Oncology Group, 899 eligible people with advanced intermediate- or high-grade non-Hodgkin lymphoma received CHOP or one of three more intensive regimens (m-BACOD, ProMACE-CytaBOM or MACOP-B), which single-institution studies had suggested might do better. Overall survival at three years was 54% with CHOP and 50% to 52% with the others (P = 0.90), and the authors concluded that CHOP remained the best available treatment. The trial predates rituximab and current definitions of DLBCL.

Evidence current to October 2026 · Checked against primary sources to the extent possible

A guided tour of 12 milestones. You can pause or step through it yourself.

Filter milestonesshowing all 26
Treatment type
Setting

Molecular origins

  1. 1976 · Treatment · ChemotherapyCHOP and HOP chemotherapy in advanced lymphoma (McKelvey, 1976)A 1976 report described people with pathologically staged, advanced non-Hodgkin lymphoma treated with CHOP, a four-drug combination, or with the three-drug HOP. Of those who could be evaluated, 71 in 100 given CHOP and 61 in 100 given HOP had a complete remission. A 1993 trial later used CHOP as its comparison regimen.Series of pathologically staged advanced non-Hodgkin's lymphoma treated with CHOP (204 evaluable patients) or HOP (216 evaluable). Complete remission 71% (CHOP) and 61% (HOP); overall response 92% and 88%. Complete remission, nodular vs diffuse: 78% vs 67% (CHOP), 67% vs 60% (HOP). Remission maintenance with COP or OAP; projected 1-year disease-free 86% and 80%.
  2. 1993 · Reversal · ChemotherapyCHOP vs three intensive regimens in advanced lymphoma (1993)Single-institution studies had suggested that more intensive chemotherapy might beat CHOP. A trial started by two US cooperative groups, in 899 eligible people with advanced intermediate- or high-grade non-Hodgkin lymphoma, compared CHOP with three such regimens. Three-year survival was 54 in 100 with CHOP and 50 to 52 in 100 with the others, with no significant difference.SWOG/ECOG phase III: 1138 registered, 899 eligible, randomised to CHOP, m-BACOD, ProMACE-CytaBOM or MACOP-B. No significant differences in response rates. Three-year alive without disease 41%, 46%, 46%, 41% (P=0.35); 3-year OS 54%, 52%, 50%, 50% (P=0.90), in the order CHOP, m-BACOD, ProMACE-CytaBOM, MACOP-B. Fatal toxic reactions 1%, 5%, 3%, 6% (P=0.09).
  3. 1993 · Understanding · UnderstandingInternational Prognostic Index for aggressive lymphoma (1993)Researchers pooled data from 2,031 adults with aggressive non-Hodgkin lymphoma, treated with doxorubicin-based chemotherapy, to see which features at diagnosis predicted outcome. Age, stage, a blood test (LDH), general fitness and the number of sites outside the lymph nodes sorted people into four groups with predicted five-year survival from 73 in 100 down to 26 in 100.Pooled analysis of 2031 adults with aggressive NHL treated 1982-1987 with doxorubicin-containing regimens at 16 institutions and cooperative groups. Age, stage, LDH, performance status and extranodal sites defined four risk groups with predicted 5-year survival 73%, 51%, 43%, 26%. Age-adjusted index (1274 patients aged 60 or younger; stage, LDH, performance status): 83%, 69%, 46%, 32%. Both were more accurate than Ann Arbor stage.
  4. 1995 · Treatment · Cell therapy & transplantPARMA: autologous transplant vs salvage chemotherapy in relapse (1995)In a randomised study of people with relapsed non-Hodgkin lymphoma whose disease had responded to two courses of chemotherapy, high-dose chemotherapy with a bone marrow transplant was compared with more conventional chemotherapy. At five years, 46 in 100 were free of events after transplant, compared with 12 in 100 after chemotherapy alone.Randomised study (PARMA) in relapsed, chemotherapy-sensitive non-Hodgkin lymphoma: 109 responders to two salvage courses were assigned to four further chemotherapy courses plus radiotherapy (54) or radiotherapy plus intensive chemotherapy and autologous bone marrow transplantation (55). Median follow-up 63 months. 5-year EFS 46% vs 12% (P=0.001); 5-year OS 53% vs 32% (P=0.038). Three deaths from toxic effects in the transplantation group, none in the other group.
  5. 1997 · Treatment · ImmunotherapyRituximab for relapsed indolent lymphoma: FDA approval and JCO reportA study of 166 people with relapsed low-grade or follicular lymphoma found that about half responded to four weekly infusions of rituximab, an antibody that targets the CD20 protein on B cells. The US FDA approved rituximab for this use in November 1997, before the trial was published.Multi-institutional study (n=166, 31 centres), relapsed low-grade or follicular lymphoma, rituximab 375 mg/m2 weekly for four doses. Response rate in the intent-to-treat group 48%; projected median time to progression in responders 13.0 months (median follow-up 11.8 months). Grade 3 toxicity 12%, grade 4 3%. FDA approval 26 November 1997 for relapsed or refractory low-grade or follicular B-cell NHL.

Targeted therapy

  1. 2000 · Understanding · UnderstandingGene expression profiling splits DLBCL into distinct types (2000)Using DNA microarrays to read gene activity in lymphoma samples, researchers found that diffuse large B-cell lymphoma splits into two molecular forms: one resembling normal germinal-centre B cells and one resembling activated B cells. People with the germinal-centre form had significantly better overall survival. The authors proposed that outcomes differ because the tumours differ in their biology.DNA-microarray gene-expression profiling of B-cell malignancies identified two molecularly distinct forms of DLBCL: germinal centre B-like and activated B-like, reflecting different stages of B-cell differentiation. Patients with germinal centre B-like DLBCL had significantly better overall survival than those with activated B-like DLBCL. The abstract gives no sample size, hazard ratio or p-value.
  2. 2002 · Treatment · ImmunotherapyR-CHOP vs CHOP in older DLBCL: GELA LNH98-5 (2002)A French trial of 399 people aged 60 to 80 with previously untreated diffuse large B-cell lymphoma compared CHOP chemotherapy with CHOP plus the antibody rituximab. Complete responses occurred in 76 in 100 people given the combination and 63 in 100 given CHOP alone. Ten years on, 44 in 100 given the combination were alive, compared with 28 in 100.Randomised trial (GELA) in 399 untreated DLBCL patients aged 60-80: eight cycles of CHOP (197) or CHOP plus rituximab (202). Complete response 76% vs 63% (P=0.005). At median follow-up of two years, EFS P<0.001 and OS P=0.007; risk ratios for treatment failure 0.58 (95% CI 0.44-0.77) and death 0.64 (0.45-0.89). At 10 years: PFS 36.5% vs 20%; OS 43.5% vs 27.6%.
  3. 2003 · De-escalation · ChemotherapyWatch and wait vs immediate chlorambucil, low-grade lymphomaA UK trial that recruited from 1981 to 1990 randomised people with advanced, symptom-free low-grade lymphoma to start chlorambucil at once or to wait until it was needed. After a median of 16 years, survival did not differ. A later trial in follicular lymphoma found that rituximab delayed the need for new treatment.Randomised trial (n=309, 44 UK centres), asymptomatic advanced-stage low-grade NHL: immediate chlorambucil versus observation. Median follow-up 16 years; median OS 5.9 versus 6.7 years (p=0.84). In the observation group the actuarial chance of not needing chemotherapy at 10 years was 19%. A separate phase 3 trial in low-tumour-burden follicular lymphoma: 3-year freedom from new treatment 46% with watchful waiting versus 88% with maintenance rituximab (HR 0.21, 95% CI 0.14 to 0.31).
  4. 2006 · Treatment · ImmunotherapyMInT: rituximab with CHOP-like therapy, young low-risk DLBCL (2006)The MabThera International Trial randomly assigned 824 people aged 18 to 60 with previously untreated, good-prognosis diffuse large B-cell lymphoma to six cycles of CHOP-like chemotherapy with or without rituximab. After about three years, 79 in 100 on the combination had been free of events, against 59 in 100, and 93 against 84 in 100 were alive.MInT: 824 patients aged 18-60, age-adjusted IPI 0-1, randomised to six cycles of CHOP-like chemotherapy plus rituximab (413) or alone (411). Median follow-up 34 months: 3-year EFS 79% vs 59% (difference 20%, 95% CI 13-27; log-rank P<0.0001); 3-year OS 93% vs 84% (P=0.0001). Six-year update (median 72 months): EFS 74.3% vs 55.8% (difference 18.5%, 11.5-25.4; P<0.0001).
  5. 2010 · Treatment · ChemotherapyCORAL: R-ICE vs R-DHAP before transplant in relapsed DLBCLThis trial compared two chemotherapy-plus-rituximab regimens used to bring relapsed lymphoma under control before a stem-cell transplant. Responses were similar, about 63 in 100 with each regimen, and survival did not differ significantly. Outcomes were worse when the lymphoma relapsed early or had already been treated with rituximab.CORAL: CD20-positive DLBCL in first relapse or refractory, randomised to R-ICE (n=202) or R-DHAP (n=194), median age 55. Overall response after three cycles 63.5% vs 62.8%; primary end point (mobilisation-adjusted response) 52.3% vs 54.5%; 3-year EFS 26% vs 35% (P=.6). Across both regimens, 3-year EFS 21% with vs 47% without prior rituximab. Rituximab maintenance after ASCT, rituximab vs observation: 4-year EFS 52% vs 53% (P=.7).
  6. 2010 · Treatment · ImmunotherapyPRIMA: two years of rituximab maintenance after induction (2010)In people with untreated follicular lymphoma who responded to rituximab plus chemotherapy, two more years of rituximab every eight weeks lowered the chance of progression: about three in four were progression-free at a median follow-up of three years, versus about three in five with observation. Infections and other serious side effects were more common.Open-label phase 3 (1217 enrolled; 1019 responders randomised, 505 to rituximab maintenance and 513 to observation). Median follow-up 36 months: PFS 74.9% versus 57.6% (HR 0.55, 95% CI 0.44 to 0.68; p<0.0001). OS HR 0.87 (95% CI 0.51 to 1.47). Grade 3-4 adverse events 24% versus 17%; grade 2-4 infections 39% versus 24%.

Immunotherapy

  1. 2013 · Reversal · ImmunotherapyR-CHOP-14 not better than R-CHOP-21 (two randomised trials, 2013)Two large randomised trials asked whether giving R-CHOP every two weeks instead of every three helps. A trial in 602 people aged 60 to 80 and a UK trial in 1,080 adults found no survival gain from the two-week schedule. In the UK trial, 2-year survival was 83 in 100 versus 81 in 100.Two separate randomised phase 3 trials, not pooled. LNH03-6B (602 patients aged 60-80, aaIPI 1 or more): 3-year EFS 56% (R-CHOP-14) vs 60% (R-CHOP-21), HR 1.04 (95% CI 0.82-1.31; P=0.7614); red-cell transfusion 47% vs 31%. UK trial (1080 adults): 2-year OS 82.7% vs 80.8%, HR 0.90 (0.70-1.15; P=0.3763); 2-year PFS 75.4% vs 74.8% (HR 0.94, 0.76-1.17).
  2. 2013 · Treatment · ChemotherapyStiL: bendamustine-rituximab vs R-CHOP, first-line indolent/MCLIn a German trial of people with newly diagnosed advanced indolent or mantle-cell lymphoma, median progression-free survival was about 70 months with bendamustine plus rituximab versus about 31 months with R-CHOP, with less hair loss, nerve damage and low blood counts. The trial mixed several lymphoma types.Open-label phase 3 non-inferiority (n=549), untreated stage III or IV indolent or mantle-cell lymphoma, bendamustine-rituximab versus R-CHOP; per-protocol analysis, median follow-up 45 months. Median PFS 69.5 versus 31.2 months (HR 0.58, 95% CI 0.44 to 0.74; p<0.0001). Peripheral neuropathy 7% versus 29%. BRIGHT (n=447): 5-year PFS 65.5% versus 55.8% (HR 0.61, 95% CI 0.45 to 0.85).
  3. 2017 · Treatment · ImmunotherapyGALLIUM: obinutuzumab vs rituximab plus chemotherapy in FL (2017)In 1,202 people with untreated advanced follicular lymphoma, chemotherapy with the antibody obinutuzumab lowered the chance of progression compared with chemotherapy with rituximab: about four in five versus about three in four were progression-free at three years. Serious side effects were more common with obinutuzumab. The FDA approved it for this use in November 2017.Randomised phase 3 (n=1202), previously untreated advanced-stage FL: obinutuzumab-based versus rituximab-based chemotherapy, then same-antibody maintenance for up to 2 years. Planned interim analysis, median follow-up 34.5 months: investigator-assessed 3-year PFS 80.0% versus 73.3% (HR 0.66, 95% CI 0.51 to 0.85; P=0.001). Grade 3-5 adverse events 74.6% versus 67.8%. FDA approval 16 November 2017.
  4. 2017 · Understanding · Chemotherapy⚑ needs reviewSCHOLAR-1: outcomes in refractory DLBCL (2017)A pooled look back at people whose diffuse large B-cell lymphoma was refractory to treatment found that about one in four responded to the next treatment and a fifth were alive at two years. It combined data from two trials and two hospital cohorts, and is not a treatment trial.SCHOLAR-1: retrospective patient-level pooling of two phase 3 trials (CORAL, LY.12) and two observational cohorts; 861 patients, 636 meeting refractory-disease criteria. Objective response to the next line of therapy 26% (CR 7%); median OS 6.3 months from the start of salvage therapy; 20% alive at 2 years. Outcomes were reported as consistently poor across subgroups and cohorts.
  5. 2017 · Treatment · Cell therapy & transplantZUMA-1 and other CD19 CAR T trials in large B-cell lymphomaIn adults whose large B-cell lymphoma had not responded to earlier treatment or had returned, three studies of CD19-directed CAR T cells reported tumour responses in about half to more than four in five of those treated. None had a comparison group. The FDA approved axicabtagene ciloleucel in October 2017.Single-arm studies in relapsed or refractory large B-cell lymphoma. ZUMA-1 (phase 2, 111 enrolled, 101 treated): ORR 82%, CR 54%; in an updated analysis of 108 patients treated in phases 1 and 2, 18-month OS 52%; at 5 years median OS 25.8 months, 5-year OS 42.6%. JULIET (tisagenlecleucel, 93 evaluated): best ORR 52% (95% CI 41 to 62), CR 40%. TRANSCEND NHL 001 (liso-cel, 256 efficacy-evaluable): ORR 73% (66.8 to 78.0), CR 53%.
  6. 2018 · Treatment · ImmunotherapyRELEVANCE: rituximab-lenalidomide vs chemoimmunotherapy (2018)In 1,030 people with untreated advanced follicular lymphoma, a chemotherapy-free pairing of lenalidomide with rituximab gave similar results to rituximab with chemotherapy, with different side effects: fewer low neutrophil counts but more skin reactions. At six years about six in ten people were free of progression in both groups.Randomised phase 3 superiority trial (n=1030), untreated FL: rituximab-lenalidomide (R2) versus rituximab-chemotherapy, both followed by rituximab maintenance. Complete response (confirmed or unconfirmed) at 120 weeks 48% versus 53% (P=0.13); interim 3-year PFS 77% versus 78%. At median follow-up 72 months: 6-year PFS 60% versus 59% (HR 1.03, 95% CI 0.84 to 1.27); 6-year OS 89% in both.
  7. 2019 · Reversal · ChemotherapyDA-EPOCH-R not better than R-CHOP: CALGB/Alliance 50303 (2019)In a US intergroup trial, 491 eligible adults with previously untreated diffuse large B-cell lymphoma received either R-CHOP or the more intensive infusional regimen DA-EPOCH-R. Progression-free and overall survival did not differ significantly. DA-EPOCH-R was more toxic, with more severe nerve damage (19 in 100 people versus 3 in 100).Alliance/CALGB 50303 (phase III, six cycles each): 524 registered, 491 eligible in the final analysis. Median follow-up 5 years: PFS HR 0.93 (95% CI 0.68-1.27; P=.65), 2-year PFS 78.9% (DA-EPOCH-R) vs 75.5% (R-CHOP); OS HR 1.09 (0.75-1.59; P=.64), 2-year OS 86.5% vs 85.7%. Grade 3-4 febrile neutropenia 35.0% vs 17.7%; neuropathy 18.6% vs 3.3%. Treatment-related deaths 2.1% in each arm.
  8. 2019 · Treatment · Antibody–drug conjugatePolatuzumab vedotin with bendamustine-rituximab: FDA 2019In a small randomised study of people with relapsed or refractory diffuse large B-cell lymphoma who could not have a stem-cell transplant, adding polatuzumab vedotin to bendamustine and rituximab raised the complete response rate from about 18 in 100 to 40 in 100. The FDA granted accelerated approval in June 2019.GO29365 randomised phase 2 cohort (80 patients, 40 per arm) in transplantation-ineligible relapsed or refractory DLBCL, pola-BR vs BR. IRC-assessed complete response at end of treatment (primary): 40.0% vs 17.5% (P=.026). Median PFS 9.5 vs 3.7 months (HR 0.36, 95% CI 0.21 to 0.63); median OS 12.4 vs 4.7 months (HR 0.42, 0.24 to 0.75; median follow-up 22.3 months). Pola-BG single-arm cohort (n=27): CR 29.6%.

Precision & engineered

  1. 2021 · Reversal · Cell therapy & transplantBELINDA: tisagenlecleucel not superior in second line (2021)In this randomised trial of tisagenlecleucel CAR T cells against salvage chemotherapy and transplant as second-line treatment for aggressive lymphoma, event-free survival did not differ: the median was 3 months in both groups. The authors concluded that tisagenlecleucel was not superior to standard salvage therapy.BELINDA: randomised phase 3, 322 patients with aggressive B-cell lymphoma refractory to or progressing within 12 months of first-line therapy; tisagenlecleucel (optional bridging) vs salvage chemotherapy and autologous HSCT. Median EFS 3.0 months in both groups; HR 1.07 (95% CI 0.82 to 1.40; P=0.61). Response 46.3% vs 42.5%. Authors: tisagenlecleucel was not superior to standard salvage therapy.
  2. 2021 · Reversal · TargetedPI3K inhibitors in FL: accelerated approvals withdrawn (2021-2024)Four targeted drugs that block the PI3K protein each received accelerated FDA approval for relapsed follicular lymphoma, from 2014 to 2021. Single-arm studies of each drug had reported response rates in indolent lymphoma. All four follicular lymphoma indications were later withdrawn, between December 2021 and March 2024.Single-arm phase 2 studies in relapsed or refractory indolent lymphoma reported: idelalisib (n=125; ORR 57%), copanlisib (n=142; ORR 59%), duvelisib (n=129; FL ORR 42.2%), umbralisib (n=208; ORR 47.1%). Each drug received FDA accelerated approval in relapsed FL. Per the FDA list, the FL indications were withdrawn on 17 December 2021 (duvelisib), 18 February 2022 (idelalisib), 31 May 2022 (umbralisib) and 18 March 2024 (copanlisib).
  3. 2021 · Treatment · Antibody–drug conjugatePOLARIX: polatuzumab vedotin with R-CHP vs R-CHOP (2021)In a trial of 879 adults with previously untreated, intermediate- or high-risk diffuse large B-cell lymphoma, replacing vincristine in R-CHOP with the antibody-drug conjugate polatuzumab vedotin lowered the risk of progression, relapse or death. After two years, 77 in 100 were free of progression versus 70 in 100. Survival did not differ significantly.POLARIX (n=879, double-blind): pola-R-CHP vs R-CHOP. Median follow-up 28.2 months: 2-year PFS 76.7% vs 70.2%, HR 0.73 (95% CI 0.57-0.95; P=0.02); 2-year OS 88.7% vs 88.6% (HR 0.94, 0.65-1.37). Five-year update (median 64.1 months): PFS HR 0.77 (0.62-0.97), 5-year PFS 64.9% vs 59.1%; OS HR 0.85 (0.63-1.15).
  4. 2021 · Treatment · Cell therapy & transplantZUMA-7 and TRANSFORM: CAR T cells vs salvage plus transplantTwo large trials compared CD19 CAR T cells with the usual second-line approach of salvage chemotherapy and, for responders, a stem-cell transplant. People whose lymphoma was resistant to first treatment or returned within a year stayed free of progression or other events for longer with CAR T cells. ZUMA-7 also reported better survival at four years.Randomised phase 3 trials in large B-cell lymphoma refractory to or relapsing within 12 months of first-line therapy. ZUMA-7 (n=359): median EFS 8.3 vs 2.0 months, HR 0.40 (95% CI 0.31 to 0.51); 4-year OS 54.6% vs 46.0% (HR 0.73, 0.54 to 0.98). TRANSFORM (n=184, interim): median EFS 10.1 vs 2.3 months, HR 0.35 (0.23 to 0.53). Different CAR T products, eligibility and designs.
  5. 2021 · Treatment · Cell therapy & transplantZUMA-5: axicabtagene ciloleucel in relapsed follicular lymphoma (2021)In a single-arm study of people with relapsed follicular or marginal zone lymphoma, nearly all responded to a one-time infusion of their own T cells engineered to target CD19, and about three in four had a complete response. The FDA gave accelerated approval for follicular lymphoma in March 2021; two other CAR T products followed.Single-arm phase 2 (ZUMA-5), relapsed or refractory indolent NHL after two or more lines. Primary analysis (n=104; 84 follicular, 20 marginal zone; median follow-up 17.5 months): ORR 92% (95% CI 85 to 97), CR 74%. Three-year report, follicular lymphoma (n=127, median follow-up 41.7 months): ORR 94%, median PFS 40.2 months. ELARA, tisagenlecleucel (n=94 efficacy set): CR rate 69.1%, ORR 86.2%.
  6. 2022 · Treatment · ImmunotherapyMosunetuzumab and epcoritamab in relapsed follicular lymphomaAntibodies that link a person's T cells to lymphoma cells produced responses in most people with relapsed follicular lymphoma in single-arm studies: complete response in about six in ten with mosunetuzumab, response in about eight in ten with epcoritamab. Both received FDA accelerated approval. A randomised trial then tested adding epcoritamab to lenalidomide and rituximab.Single-arm phase 2 studies, relapsed or refractory FL after two or more lines. Mosunetuzumab (n=90): IRC-assessed CR rate 60.0% (95% CI 49.1 to 70.2). Epcoritamab (pivotal cohort n=128): ORR 82.0%, CR rate 62.5%. Randomised phase 3 EPCORE FL-1 (n=488, interim analysis, median follow-up 14.8 months): ORR 95% versus 79%; 16-month PFS 85.5% versus 40.2% (HR 0.21, 95% CI 0.14 to 0.31).
  7. 2022 · Treatment · ImmunotherapyGlofitamab and epcoritamab in relapsed DLBCL (2022-2023)Two antibodies that link T cells to CD20-carrying lymphoma cells, glofitamab and epcoritamab, produced complete responses in about 4 in 10 heavily pretreated people with large B-cell lymphoma in single-arm studies. The FDA granted both accelerated approval in 2023.Single-arm phase 2 reports in relapsed or refractory large B-cell lymphoma after at least two lines. Glofitamab (fixed-duration, 155 enrolled): IRC complete response 39% (95% CI 32 to 48), median follow-up 12.6 months; 12-month PFS 37%. Epcoritamab (subcutaneous, 157 treated): ORR 63.1% (55.0 to 70.6), CR 38.9%; at 25.1 months CR 40.1%, 24-month PFS 27.8%. FDA accelerated approvals 19 May and 15 June 2023.

Then and now

  • 5-year relative survival · United States, SEER 8 registries

    • 36.05%

      1975 (observed value; first year in the table)

    Diffuse large B-cell lymphoma (DLBCL); all races, both sexes; SEER 8 five-year relative survival series, 1975-2018, on the SEER Cancer Stat Facts DLBCL page. Age range and stage mix are not stated for this series.

    Relative survival excludes deaths from other causes. 'Observed' is the table's label for the actual yearly value, as opposed to the modeled trend value in the adjacent column. The table column is headed 'Year' and the caption beneath the chart reads 'SEER 8 5-Year Relative Survival Percent from 1975-2018, All Races, Both Sexes'; neither labels the year as year of diagnosis. SEER 8 covers a limited set of registries. Modeled trend value for the same year: 41.41%. Single-year values fluctuate (this is the lowest observed value in the series; the highest is 70.78% in 2018). The page does not list the histologies or codes behind 'diffuse large B-cell lymphoma'. The page does not describe changes over time in classification, diagnostic practice, staging, age mix or treatment, does not apportion any change and attributes it to no cause. Compare only with other values from the same SEER 8 series, and read them beside the death-rate values.

    Source

  • 5-year relative survival · United States, SEER 8 registries

    • 70.78%

      2018 (observed value; last observed year in the table)

    Diffuse large B-cell lymphoma (DLBCL); all races, both sexes; SEER 8 five-year relative survival series, 1975-2018. Age range and stage mix are not stated for this series.

    Relative survival excludes deaths from other causes. 'Observed' is the table's label for the actual yearly value, as opposed to the modeled trend value in the adjacent column. The table column is headed 'Year' and the caption beneath the chart reads 'SEER 8 5-Year Relative Survival Percent from 1975-2018, All Races, Both Sexes'; neither labels the year as year of diagnosis. SEER 8 covers a limited set of registries. Modeled trend value for the same year: 68.08%. The table shows no observed five-year value for 2019 onward (modeled values only). The SEER 21 2016-2022 value on the same page (64.8%) is a different registry set and period and must not be read as a decline. The page does not list the histologies or codes behind 'diffuse large B-cell lymphoma'. The page does not describe changes over time in classification, diagnostic practice, staging, age mix or treatment, does not apportion any change and attributes it to no cause. Compare only with other values from the same SEER 8 series, and read them beside the death-rate values.

    Source

  • 5-year relative survival · United States, SEER 21 (excluding IL)

    • 64.8%

      2016-2022

    Diffuse large B-cell lymphoma (DLBCL); the headline five-year relative survival figure on the SEER Cancer Stat Facts DLBCL page (SEER 21, excluding IL), all stages. Race, sex and age range are not stated beside the figure; the page's other tables are labelled all races, both sexes.

    A different registry set and period from the SEER 8 series, so it is not a continuation of the 1975-2018 values and must not be subtracted from them. It is lower than the SEER 8 observed value for 2018 (70.78%); the page does not explain the difference, so it must not be read as a decline in survival. The page labels the period '2016-2022' and does not say whether this is year of diagnosis. Relative survival excludes deaths from other causes. The page's sex, age and race breakdown of this figure is a separate table.

    Source

  • 5-year relative survival · United States, SEER 17 registries

    • 79.9%

      2016-2022; stage I at diagnosis (20% of cases)

    Diffuse large B-cell lymphoma (DLBCL), all races, both sexes, by Ann Arbor stage at diagnosis (SEER 17, 2016-2022, per the page's stage table); the page's label for stage I is 'Confined to Single Region'.

    Stage-specific value from the page's 'Survival by Stage' table (stage mix on the page: 20% I, 19% II, 16% III, 40% IV, 5% unstaged; the text gives 19.6% for stage I). Five-year relative survival on the page is 76.0% for stage II, 67.5% for stage III and 54.6% for unstaged cases. The page states that statistics by stage include only cases coded as lymphoma or lymphoma-CLL/SLL in the EOD 2018 schema, and that stage at diagnosis has a strong influence on survival. A different registry set (SEER 17) and period from the SEER 8 series and the SEER 21 headline figure, so do not subtract or chain them.

    Source

  • 5-year relative survival · United States, SEER 17 registries

    • 56.3%

      2016-2022; stage IV at diagnosis (40% of cases)

    Diffuse large B-cell lymphoma (DLBCL), all races, both sexes, by Ann Arbor stage at diagnosis (SEER 17, 2016-2022); the page's label for stage IV is 'Diffuse or Disseminated Involvement'.

    Stage-specific value from the page's 'Survival by Stage' table; stage IV is the largest stage group on the page (40% of cases). The page states that statistics by stage include only cases coded as lymphoma or lymphoma-CLL/SLL in the EOD 2018 schema. A different registry set (SEER 17) and period from the SEER 8 series and the SEER 21 headline figure, so do not subtract or chain them. Five-year figure only.

    Source

  • 5-year relative survival · United States, SEER 8 registries

    • 66.05%

      1975 (observed value; first year in the table)

    Follicular lymphoma; all races, both sexes; SEER 8 five-year relative survival series, 1975-2018, on the SEER Cancer Stat Facts follicular lymphoma page. Age range and stage mix are not stated for this series.

    Relative survival excludes deaths from other causes. 'Observed' is the table's label for the actual yearly value, as opposed to the modeled trend value in the adjacent column. The table column is headed 'Year' and the caption beneath the chart reads 'SEER 8 5-Year Relative Survival Percent from 1975-2018, All Races, Both Sexes'; neither labels the year as year of diagnosis. SEER 8 covers a limited set of registries. Modeled trend value for the same year: 60.59%. Single-year values fluctuate widely in this series (for example 55.29% in 1977 and 93.78% in 2014), so one start year and one end year do not describe the path between them. The page does not list the histologies or codes behind 'follicular lymphoma'. The page describes follicular lymphoma as usually indolent, so a five-year figure describes only part of a long course. The page does not describe changes over time in classification, diagnostic practice, staging, age mix or treatment, does not apportion any change and attributes it to no cause. Compare only with other values from the same SEER 8 series, and read them beside the death-rate values.

    Source

  • 5-year relative survival · United States, SEER 8 registries

    • 92.82%

      2018 (observed value; last observed year in the table)

    Follicular lymphoma; all races, both sexes; SEER 8 five-year relative survival series, 1975-2018. Age range and stage mix are not stated for this series.

    Relative survival excludes deaths from other causes. 'Observed' is the table's label for the actual yearly value, as opposed to the modeled trend value in the adjacent column. The table column is headed 'Year' and the caption beneath the chart reads 'SEER 8 5-Year Relative Survival Percent from 1975-2018, All Races, Both Sexes'; neither labels the year as year of diagnosis. SEER 8 covers a limited set of registries. Modeled trend value for the same year: 91.75%. The table shows no observed five-year value for 2019 onward (modeled values only). The SEER 21 2016-2022 value on the same page (88.9%) is a different registry set and period and must not be read as a decline. The page does not list the histologies or codes behind 'follicular lymphoma'. The page describes follicular lymphoma as usually indolent, so a five-year figure describes only part of a long course. The page does not describe changes over time in classification, diagnostic practice, staging, age mix or treatment, does not apportion any change and attributes it to no cause. Compare only with other values from the same SEER 8 series, and read them beside the death-rate values.

    Source

  • 5-year relative survival · United States, SEER 21 (excluding IL)

    • 88.9%

      2016-2022

    Follicular lymphoma; the headline five-year relative survival figure on the SEER Cancer Stat Facts follicular lymphoma page (SEER 21, excluding IL), all stages. Race, sex and age range are not stated beside the figure; the page's other tables are labelled all races, both sexes.

    A different registry set and period from the SEER 8 series, so it is not a continuation of the 1975-2018 values and must not be subtracted from them. It is lower than the SEER 8 observed value for 2018 (92.82%); the page does not explain the difference, so it must not be read as a decline in survival. The page labels the period '2016-2022' and does not say whether this is year of diagnosis. Relative survival excludes deaths from other causes.

    Source

  • 5-year relative survival · United States, SEER 17 registries

    • 97.2%

      2016-2022; stage I at diagnosis (23% of cases)

    Follicular lymphoma, all races, both sexes, by Ann Arbor stage at diagnosis (SEER 17, 2016-2022, per the page's stage table); the page's label for stage I is 'Confined to Single Region'.

    Stage-specific value from the page's 'Survival by Stage' table (stage mix on the page: 23% I, 15% II, 27% III, 28% IV, 8% unstaged; the text gives 22.6% for stage I). Five-year relative survival on the page is 91.1% for stage II, 88.7% for stage III and 88.2% for unstaged cases. The page states that statistics by stage include only cases coded as lymphoma or lymphoma-CLL/SLL in the EOD 2018 schema. A different registry set (SEER 17) and period from the SEER 8 series and the SEER 21 headline figure, so do not subtract or chain them.

    Source

  • 5-year relative survival · United States, SEER 17 registries

    • 82.3%

      2016-2022; stage IV at diagnosis (28% of cases)

    Follicular lymphoma, all races, both sexes, by Ann Arbor stage at diagnosis (SEER 17, 2016-2022); the page's label for stage IV is 'Diffuse or Disseminated Involvement'.

    Stage-specific value from the page's 'Survival by Stage' table. The page states that statistics by stage include only cases coded as lymphoma or lymphoma-CLL/SLL in the EOD 2018 schema. A different registry set (SEER 17) and period from the SEER 8 series and the SEER 21 headline figure, so do not subtract or chain them. Five-year figure only.

    Source

  • 5-year relative survival · United States, SEER 8 registries

    • 46.64%

      1975 (observed value; first year in the table)

    All non-Hodgkin lymphoma; all races, both sexes; SEER 8 five-year relative survival series, 1975-2018, on the SEER Cancer Stat Facts non-Hodgkin lymphoma page. Age range and stage mix are not stated for this series. This is a different category from the DLBCL and follicular lymphoma series above and is not their sum or average.

    Relative survival excludes deaths from other causes. 'Observed' is the table's label for the actual yearly value, as opposed to the modeled trend value in the adjacent column. The table column is headed 'Year' and the caption beneath the chart reads 'SEER 8 5-Year Relative Survival Percent from 1975-2018, All Races, Both Sexes'; neither labels the year as year of diagnosis. SEER 8 covers a limited set of registries. Modeled trend value for the same year: 47.98%. The highest observed value in the series is 78.4% in 2015. The NHL category combines many lymphoma types (the page names B-cell, T-cell and NK-cell types and describes diffuse large B-cell lymphoma and follicular lymphoma as the two most common in adults), so the mix of types is part of any change over time; the page does not report that mix. The page does not describe changes over time in classification, diagnostic practice, staging, age mix or treatment, does not apportion any change and attributes it to no cause. Compare only with other values from the same SEER 8 series, and read them beside the death-rate values.

    Source

  • 5-year relative survival · United States, SEER 8 registries

    • 77.93%

      2018 (observed value; last observed year in the table)

    All non-Hodgkin lymphoma; all races, both sexes; SEER 8 five-year relative survival series, 1975-2018. Age range and stage mix are not stated for this series.

    Relative survival excludes deaths from other causes. 'Observed' is the table's label for the actual yearly value, as opposed to the modeled trend value in the adjacent column. The table column is headed 'Year' and the caption beneath the chart reads 'SEER 8 5-Year Relative Survival Percent from 1975-2018, All Races, Both Sexes'; neither labels the year as year of diagnosis. SEER 8 covers a limited set of registries. Modeled trend value for the same year: 76.90%. The table shows no observed five-year value for 2019 onward (modeled values only; 72.56% modeled for 2023). The SEER 21 2016-2022 value on the same page (74.3%) is a different registry set and period and must not be read as a decline. The NHL category combines many lymphoma types (the page names B-cell, T-cell and NK-cell types and describes diffuse large B-cell lymphoma and follicular lymphoma as the two most common in adults), so the mix of types is part of any change over time; the page does not report that mix. The page does not describe changes over time in classification, diagnostic practice, staging, age mix or treatment, does not apportion any change and attributes it to no cause. Compare only with other values from the same SEER 8 series, and read them beside the death-rate values.

    Source

  • 5-year relative survival · United States, SEER 21 (excluding IL)

    • 74.3%

      2016-2022

    All non-Hodgkin lymphoma; the headline five-year relative survival figure on the SEER Cancer Stat Facts non-Hodgkin lymphoma page (SEER 21, excluding IL), all stages. Race, sex and age range are not stated beside the figure.

    A different registry set and period from the SEER 8 series, so it is not a continuation of the 1975-2018 values and must not be subtracted from them. It is lower than the SEER 8 observed value for 2018 (77.93%); the page does not explain the difference, so it must not be read as a decline in survival. The page labels the period '2016-2022' and does not say whether this is year of diagnosis. Relative survival excludes deaths from other causes.

    Source

  • Age-standardised mortality · United States, SEER 8 (incidence-based mortality)

    • 2.8per 100,000

      1992 (observed; first year with a value in the table)

    Diffuse large B-cell lymphoma; all races, both sexes; age-adjusted death rate, 'Death Rate - SEER 8 Incidence-Based Mortality' column of the table on the SEER Cancer Stat Facts DLBCL page.

    Observed value from the table; the adjacent modeled trend column is not used. The chart note states that deaths come from SEER 8 Incidence-Based Mortality (all races, both sexes, age-adjusted), a different series from the 'U.S. Mortality' death rate on the non-Hodgkin lymphoma page; the death-rate columns of the table start in 1992 (earlier cells are '-'). Death rates describe the whole population and are not measured from the date of diagnosis, so they are not a survival measure and depend on how many people are diagnosed. In the same table the age-adjusted SEER 8 rate of new cases was 3.14 per 100,000 in 1975, 6.45 in 1995 (the highest value) and 5.08 in 2023; the page text says new cases fell on average 0.8% a year over 2014-2023 and death rates were stable over 2014-2023. The page does not say how the diagnostic category was coded across the years or attribute the change in the rate to a cause.

    Source

  • Age-standardised mortality · United States, SEER 8 (incidence-based mortality)

    • 1.53per 100,000

      2023 (observed; last year in the table)

    Diffuse large B-cell lymphoma; all races, both sexes; age-adjusted death rate, 'Death Rate - SEER 8 Incidence-Based Mortality' column of the table on the SEER Cancer Stat Facts DLBCL page.

    Observed value from the table; the adjacent modeled trend column is not used. The chart note states that deaths come from SEER 8 Incidence-Based Mortality (all races, both sexes, age-adjusted), a different series from the 'U.S. Mortality' death rate on the non-Hodgkin lymphoma page; the death-rate columns of the table start in 1992 (earlier cells are '-'). Death rates describe the whole population and are not measured from the date of diagnosis, so they are not a survival measure and depend on how many people are diagnosed. This is also the lowest value in the series. The headline death rate on the page is 1.7 per 100,000 (2019-2023 deaths), a five-year pooled figure.

    Source

  • Age-standardised mortality · United States, SEER 8 (incidence-based mortality)

    • 1.59per 100,000

      1992 (observed; first year with a value in the table)

    Follicular lymphoma; all races, both sexes; age-adjusted death rate, 'Death Rate - SEER 8 Incidence-Based Mortality' column of the table on the SEER Cancer Stat Facts follicular lymphoma page.

    Observed value from the table; the adjacent modeled trend column is not used. The chart note states that deaths come from SEER 8 Incidence-Based Mortality (all races, both sexes, age-adjusted), a different series from the 'U.S. Mortality' death rate on the non-Hodgkin lymphoma page; the death-rate columns of the table start in 1992 (earlier cells are '-'). Death rates describe the whole population and are not measured from the date of diagnosis, so they are not a survival measure and depend on how many people are diagnosed. In the same table the age-adjusted SEER 8 rate of new cases was 1.56 per 100,000 in 1975, 3.99 in 1986 (the highest value) and 2.32 in 2023; the page text says new cases fell on average 1.3% a year over 2014-2023 and death rates were stable over 2014-2023. The page does not say how the diagnostic category was coded across the years or attribute the change in the rate to a cause.

    Source

  • Age-standardised mortality · United States, SEER 8 (incidence-based mortality)

    • 0.34per 100,000

      2023 (observed; last year in the table)

    Follicular lymphoma; all races, both sexes; age-adjusted death rate, 'Death Rate - SEER 8 Incidence-Based Mortality' column of the table on the SEER Cancer Stat Facts follicular lymphoma page.

    Observed value from the table; the adjacent modeled trend column is not used. The chart note states that deaths come from SEER 8 Incidence-Based Mortality (all races, both sexes, age-adjusted), a different series from the 'U.S. Mortality' death rate on the non-Hodgkin lymphoma page; the death-rate columns of the table start in 1992 (earlier cells are '-'). Death rates describe the whole population and are not measured from the date of diagnosis, so they are not a survival measure and depend on how many people are diagnosed. The same value (0.34) is also shown for 2020, the lowest in the series. The headline death rate on the page is 0.4 per 100,000 (2019-2023 deaths), a five-year pooled figure.

    Source

  • Age-standardised mortality · United States

    • 5.62per 100,000

      1975 (observed; first year in the table)

    All non-Hodgkin lymphoma; all races, both sexes; age-adjusted death rate from US mortality data (the 'Death Rate - U.S.' column of the table on the SEER Cancer Stat Facts non-Hodgkin lymphoma page).

    Observed value from the table; the adjacent modeled trend column is not used. The chart note states that deaths come from U.S. Mortality (all races, both sexes, age-adjusted), not from SEER registries, so this series is not the same as the incidence-based mortality series on the DLBCL and follicular lymphoma pages. Death rates describe the whole US population and are not measured from the date of diagnosis, so they are not a survival measure and depend on how many people are diagnosed. In the same table the age-adjusted SEER 8 rate of new cases was 11.02 per 100,000 in 1975, 21.24 in 2007 (the highest value) and 18.37 in 2023. The page does not attribute the changes to a cause.

    Source

  • Age-standardised mortality · United States

    • 8.88per 100,000

      1997 (observed; highest value in the 1975-2024 table)

    All non-Hodgkin lymphoma; all races, both sexes; age-adjusted death rate from US mortality data.

    Observed value from the table; the adjacent modeled trend column is not used. The chart note states that deaths come from U.S. Mortality (all races, both sexes, age-adjusted), not from SEER registries, so this series is not the same as the incidence-based mortality series on the DLBCL and follicular lymphoma pages. Death rates describe the whole US population and are not measured from the date of diagnosis, so they are not a survival measure and depend on how many people are diagnosed. Shown because the death-rate series rose before it fell; the page does not comment on the peak or attribute it to a cause.

    Source

  • Age-standardised mortality · United States

    • 4.48per 100,000

      2024 (observed; last year in the table)

    All non-Hodgkin lymphoma; all races, both sexes; age-adjusted death rate from US mortality data.

    Observed value from the table; the adjacent modeled trend column is not used. The chart note states that deaths come from U.S. Mortality (all races, both sexes, age-adjusted), not from SEER registries, so this series is not the same as the incidence-based mortality series on the DLBCL and follicular lymphoma pages. Death rates describe the whole US population and are not measured from the date of diagnosis, so they are not a survival measure and depend on how many people are diagnosed. The page text says death rates fell on average 2.4% a year over 2015-2024 and new cases fell on average 0.6% a year over 2014-2023. The headline death rate is 4.8 per 100,000 (2020-2024 deaths), a five-year pooled figure.

    Source

  • 5-year relative survival · England (Cancer Research UK patient information page)

    • 65%

      Diagnosed 2016-2020, followed up to 2021

    People diagnosed with non-Hodgkin lymphoma in England; the page words it as 'around 65 out of every 100 people (around 65%)' surviving their cancer for 5 years or more. All lymphoma types together.

    A different country, data source and method from the SEER series: do not compare or subtract. The page describes this as net survival (NHS England data) and rounds it to 'around 65%'; net survival is not the same measure as SEER relative survival, so it is entered under the nearest available metric. The page was last reviewed 9 May 2024 (as printed).

    Source

  • 5-year relative survival · England, one area (Haematological Malignancy Research Network)

    • 60%

      Diagnosed 2010-2019

    People diagnosed with diffuse large B-cell lymphoma in one area of England; the Cancer Research UK page words it as 'around 60 in 100 people (around 60%)' surviving 5 years or more. The page identifies the source as the Haematological Malignancy Research Network (HMRN) and says the statistics are relative survival for ICD-O-3 code 9680/3.

    A different country, data source and method from the SEER series: do not compare or subtract. A regional, rounded figure ('around 60%') for people diagnosed over ten years, not national and not comparable with the SEER series or with the national net-survival figure. The page text read gives no breakdown of the figure by age or stage.

    Source

  • 5-year relative survival · England, one area (Haematological Malignancy Research Network)

    • 85%

      Diagnosed 2010-2019

    People diagnosed with follicular lymphoma in one area of England; the Cancer Research UK page words it as 'around 85 in 100 people (around 85%)' surviving their cancer for 5 years or more. The page identifies the source as the Haematological Malignancy Research Network (HMRN) and says the statistics are relative survival for ICD-O-3 codes 9690/3 and 9698/3.

    A different country, data source and method from the SEER series: do not compare or subtract. A regional, rounded figure ('around 85%') for people diagnosed over ten years, not national and not comparable with the SEER series or with the national net-survival figure. The page also gives rounded figures by FLIPI prognostic group, which are not entered.

    Source

Survival figures are affected by earlier detection (lead time) and overdiagnosis, and by changes in who is diagnosed. For screened cancers, read them alongside mortality.

Evidence chains

A lane follows one defined population and setting, where each new trial tests against what was then standard. Compare only within a lane, and read every comparison as illustrative.

DLBCL, first line: progression-free survival at 2 years

Adults with previously untreated diffuse large B-cell lymphoma. The UK R-CHOP-14 versus R-CHOP-21 trial enrolled adults aged 18 or older with bulky stage IA to IV disease; CALGB/Alliance 50303 enrolled adults; POLARIX enrolled intermediate- or high-risk disease (the FDA indication is limited to an International Prognostic Index score of 2 or greater). GELA LNH98-5 enrolled people aged 60 to 80. · Locally advanced · endpoint: PFS

Results are not comparable across trials.

The three drawn values are progression-free survival rates at 24 months, but the trials ask different questions (R-CHOP every 14 days against every 21 days, an infusional intensified regimen against R-CHOP, and polatuzumab vedotin in place of vincristine) in different eras and populations. The UK trial's primary endpoint was overall survival; POLARIX was double-blind with investigator-assessed progression-free survival. The CALGB/Alliance authors caution that more favourable R-CHOP results than historical controls may reflect patient selection. GELA LNH98-5 (older patients, CHOP with and without rituximab) reports progression-free survival at 10 years, a different time point, so it is listed but not drawn. Compare only each trial's own two arms; the chart is not a pooled estimate or a ranking of regimens.

Each pair shows one trial: its control arm and its experimental arm. Yesterday's experimental arm is often today's control. Populations, definitions and follow-up differ.

020406080100PFS at 24 months (%)201320192021ncri-r-chop-14-vs-21CALGB 50303POLARIX
  • experimental arm
  • control arm
  • different endpoint from the lane's
  • step line through experimental values
PFS at 24 months, rate, across 3 trials in this lane. ncri-r-chop-14-vs-21 (2013): experimental 75.4 % vs control 74.8 %; CALGB 50303 (2019): experimental 78.9 % vs control 75.5 %; POLARIX (2021): experimental 76.7 % vs control 70.2 %.
Data table
TrialYearEndpointControl (%)Experimental (%)
ncri-r-chop-14-vs-212013PFS74.8 %75.4 %
CALGB 503032019PFS75.5 %78.9 %
POLARIX2021PFS70.2 %76.7 %

DLBCL, first line: event-free survival at 3 years

Adults with previously untreated diffuse large B-cell lymphoma in two populations: MInT enrolled people aged 18 to 60 with an age-adjusted International Prognostic Index of 0 or 1; LNH03-6B enrolled people aged 60 to 80 with at least one adverse prognostic factor. · Locally advanced · endpoint: EFS

Results are not comparable across trials.

The two drawn values are event-free survival at about 36 months, but the populations (young good-prognosis against older with adverse factors), questions (rituximab added to CHOP-like chemotherapy against R-CHOP every 14 days against every 21 days) and eras differ. MInT used a choice of CHOP-like regimens with radiotherapy to bulky and extranodal sites, and its abstract does not say whether the 3-year figures are intention-to-treat or per-protocol; LNH03-6B gave eight cycles in both arms and is a final analysis. Compare only each trial's own two arms; the chart is not a pooled estimate.

Each pair shows one trial: its control arm and its experimental arm. Yesterday's experimental arm is often today's control. Populations, definitions and follow-up differ.

020406080100EFS at 36 months (%)20062013MInTLNH03-6B
  • experimental arm
  • control arm
  • different endpoint from the lane's
  • step line through experimental values
EFS at 36 months, rate, across 2 trials in this lane. MInT (2006): experimental 79 % vs control 59 %; LNH03-6B (2013): experimental 56 % vs control 60 %.
Data table
TrialYearEndpointControl (%)Experimental (%)
MInT2006EFS59 %79 %
LNH03-6B2013EFS60 %56 %

DLBCL, second line: CAR T cells against salvage chemotherapy and transplant

Adults with large B-cell lymphoma that was refractory to first-line chemoimmunotherapy or relapsed within 12 months, intended for salvage chemotherapy and autologous stem-cell transplantation (ZUMA-7, TRANSFORM, BELINDA). PARMA and CORAL, listed here but not drawn, enrolled earlier populations after relapse. · Relapsed / refractory · endpoint: EFS

Results are not comparable across trials.

The three drawn values are median event-free survival from each trial's primary or prespecified interim report. In all three the comparison arm was salvage immunochemotherapy followed by high-dose chemotherapy with autologous stem-cell transplantation in responders, and crossover to CAR T therapy was possible: BELINDA allowed crossover after a defined event at or after week 12, and the TRANSFORM 3-year report says 66% (61 of 92) of the standard-of-care arm were approved for crossover; this project's ZUMA-7 record does not describe crossover. Overall survival comparisons in these trials need that in mind. Definitions of early relapse and refractory disease, event definitions, bridging-therapy rules and the CAR T products differ, and TRANSFORM's first report is a prespecified interim analysis. PARMA (relapsed lymphoma that responded to two courses of chemotherapy, before rituximab, 5-year event-free rates) and CORAL (two salvage regimens, 3-year rates) answer different questions and report landmark rates, so they are listed but not drawn. Compare only each trial's own two arms; results are not pooled or ranked.

Each pair shows one trial: its control arm and its experimental arm. Yesterday's experimental arm is often today's control. Populations, definitions and follow-up differ.

02468101214EFS, median (months)202120212021ZUMA-7TRANSFORMBELINDA
  • experimental arm
  • control arm
  • different endpoint from the lane's
  • step line through experimental values
EFS, median, across 3 trials in this lane. ZUMA-7 (2021): experimental 8.3 months vs control 2 months; TRANSFORM (2021): experimental 10.1 months vs control 2.3 months; BELINDA (2021): experimental 3 months vs control 3 months.
Data table
TrialYearEndpointControl (months)Experimental (months)
ZUMA-72021EFS2 months8.3 months
TRANSFORM2021EFS2.3 months10.1 months
BELINDA2021EFS3 months3 months

DLBCL, relapsed or refractory, not eligible for transplant: polatuzumab vedotin with bendamustine-rituximab

Adults with relapsed or refractory diffuse large B-cell lymphoma who could not receive a stem-cell transplant, in the randomised cohort of the GO29365 phase Ib/II trial (40 patients per arm). · Relapsed / refractory · endpoint: PFS

Results are not comparable across trials.

One small randomised phase II cohort of 40 patients per arm; its primary endpoint was complete response, so the progression-free survival medians (independent review) are not primary-endpoint results. The bendamustine-rituximab arm was slightly older. The single-arm cohort with obinutuzumab in place of rituximab is not drawn. The single-arm CAR T and bispecific antibody studies in later-line large B-cell lymphoma have no comparison arm and are not drawn or compared with this trial. Only this trial's own two arms are compared.

Each pair shows one trial: its control arm and its experimental arm. Yesterday's experimental arm is often today's control. Populations, definitions and follow-up differ.

02468101214PFS, median (months)2019GO29365
  • experimental arm
  • control arm
  • different endpoint from the lane's
  • step line through experimental values
PFS, median, across 1 trial in this lane. GO29365 (2019): experimental 9.5 months vs control 3.7 months.
Data table
TrialYearEndpointControl (months)Experimental (months)
GO293652019PFS3.7 months9.5 months

Follicular lymphoma, first line: progression-free survival at 3 years

Adults with previously untreated advanced-stage follicular lymphoma (GALLIUM, RELEVANCE). StiL, listed but not drawn, enrolled advanced indolent or mantle-cell lymphoma, not follicular lymphoma alone. · Locally advanced · endpoint: PFS

Results are not comparable across trials.

The two drawn values are progression-free survival rates at 3 years, but the questions differ: GALLIUM compared obinutuzumab with rituximab, each with chemotherapy and maintenance, in a planned interim analysis of investigator-assessed progression-free survival (the abstract does not name the chemotherapy partners); RELEVANCE was designed as a superiority trial of rituximab plus lenalidomide against rituximab plus chemotherapy (investigator's choice of one of three regimens) and reported similar efficacy, with the 3-year value from an interim analysis. StiL reports median progression-free survival (per-protocol, non-inferiority, mixed lymphoma types) and BRIGHT, in the same milestone, reports 5-year rates, so neither shares this lane's time point and they are not drawn. Compare only each trial's own two arms; the chart is not a ranking of regimens.

Each pair shows one trial: its control arm and its experimental arm. Yesterday's experimental arm is often today's control. Populations, definitions and follow-up differ.

020406080100PFS at 36 months (%)20172018GALLIUMRELEVANCE
  • experimental arm
  • control arm
  • different endpoint from the lane's
  • step line through experimental values
PFS at 36 months, rate, across 2 trials in this lane. GALLIUM (2017): experimental 80 % vs control 73.3 %; RELEVANCE (2018): experimental 77 % vs control 78 %.
Data table
TrialYearEndpointControl (%)Experimental (%)
GALLIUM2017PFS73.3 %80 %
RELEVANCE2018PFS78 %77 %

Follicular lymphoma: rituximab maintenance after induction

Adults with untreated follicular lymphoma needing systemic therapy who responded to one of three non-randomised rituximab-chemotherapy induction regimens, then were randomised to maintenance or observation (PRIMA). · Maintenance · endpoint: PFS

Results are not comparable across trials.

PRIMA asks a different question from the induction trials (maintenance against observation after a response) and randomises responders only, after non-randomised induction. The drawn values are progression-free survival estimates at a median follow-up of 36 months, not a fixed landmark. Overall survival did not differ significantly at that follow-up. Do not read these values against the first-line induction lane. Only this trial's own two arms are compared.

Each pair shows one trial: its control arm and its experimental arm. Yesterday's experimental arm is often today's control. Populations, definitions and follow-up differ.

020406080100PFS (%)2010PRIMA
  • experimental arm
  • control arm
  • different endpoint from the lane's
  • step line through experimental values
PFS, rate, across 1 trial in this lane. PRIMA (2010): experimental 74.9 % vs control 57.6 %.
Data table
TrialYearEndpointControl (%)Experimental (%)
PRIMA2010PFS57.6 %74.9 %

Follicular lymphoma, relapsed or refractory: epcoritamab added to lenalidomide-rituximab

Adults with relapsed or refractory follicular lymphoma after at least one previous line of chemoimmunotherapy, randomised to epcoritamab plus lenalidomide and rituximab (R2) or R2 alone (EPCORE FL-1). · Relapsed / refractory · endpoint: PFS

Results are not comparable across trials.

Only one randomised trial is drawn: EPCORE FL-1, a planned interim analysis with a median follow-up of 14.8 months and estimated 16-month progression-free survival by independent review; the abstract reports no overall survival comparison. The single-arm studies in the same milestone (mosunetuzumab, EPCORE NHL-1 follicular cohorts) have no comparison arm, differ in population and endpoint, and cannot be compared with each other or with this trial. The other relapsed follicular lymphoma milestones (rituximab 1997, PI3K inhibitors, CAR T cells) are single-arm studies and are not part of this lane. Only this trial's own two arms are compared.

Each pair shows one trial: its control arm and its experimental arm. Yesterday's experimental arm is often today's control. Populations, definitions and follow-up differ.

020406080100PFS at 16 months (%)2022EPCORE FL-1
  • experimental arm
  • control arm
  • different endpoint from the lane's
  • step line through experimental values
PFS at 16 months, rate, across 1 trial in this lane. EPCORE FL-1 (2022): experimental 85.5 % vs control 40.2 %.
Data table
TrialYearEndpointControl (%)Experimental (%)
EPCORE FL-12022PFS40.2 %85.5 %

Standard of care, then and now

How the usual sequence of treatment changed for one setting. Choose a point in time; each step links to the milestone behind it.

DLBCL: first-line chemoimmunotherapy

Adults with previously untreated diffuse large B-cell lymphoma · Locally advanced

  1. Immunotherapy1Rituximab added to CHOP (age 60 to 80)R-CHOP vs CHOP in older DLBCL: GELA LNH98-5 (2002) (2002)
  2. Immunotherapy2Rituximab added to CHOP-like (age 18 to 60)MInT: rituximab with CHOP-like therapy, young low-risk DLBCL (2006) (2006)
  3. Chemotherapy3R-CHOP every 14 vs 21 days: no survival gainR-CHOP-14 not better than R-CHOP-21 (two randomised trials, 2013) (2013)
  4. Chemotherapy4DA-EPOCH-R vs R-CHOP: no significant gainDA-EPOCH-R not better than R-CHOP: CALGB/Alliance 50303 (2019) (2019)
  5. Antibody–drug conjugate5Polatuzumab vedotin with R-CHP vs R-CHOPPOLARIX: polatuzumab vedotin with R-CHP vs R-CHOP (2021) (2021)
2021. Based only on the trials cited in each step. Polatuzumab vedotin replaced vincristine in the R-CHP backbone in a randomised trial; progression-free survival was higher, with no significant survival difference.
Text version
  • 1993: CHOP chemotherapy → Intensive regimens vs CHOP: no difference
  • 2006: CHOP chemotherapy → Intensive regimens vs CHOP: no difference → Rituximab added to CHOP (age 60 to 80) → Rituximab added to CHOP-like (age 18 to 60)
  • 2019: Rituximab added to CHOP (age 60 to 80) → Rituximab added to CHOP-like (age 18 to 60) → R-CHOP every 14 vs 21 days: no survival gain → DA-EPOCH-R vs R-CHOP: no significant gain
  • 2021: Rituximab added to CHOP (age 60 to 80) → Rituximab added to CHOP-like (age 18 to 60) → R-CHOP every 14 vs 21 days: no survival gain → DA-EPOCH-R vs R-CHOP: no significant gain → Polatuzumab vedotin with R-CHP vs R-CHOP

Follicular lymphoma: first-line approaches

Adults with previously untreated advanced-stage indolent or follicular lymphoma · Locally advanced

  1. Understanding1Watchful waiting vs immediate chlorambucilWatch and wait vs immediate chlorambucil, low-grade lymphoma (2003)
  2. Chemotherapy2Bendamustine-rituximab vs R-CHOPStiL: bendamustine-rituximab vs R-CHOP, first-line indolent/MCL (2013)
  3. Immunotherapy3Obinutuzumab vs rituximab, with chemotherapyGALLIUM: obinutuzumab vs rituximab plus chemotherapy in FL (2017) (2017)
  4. Targeted4Rituximab-lenalidomide vs R-chemotherapyRELEVANCE: rituximab-lenalidomide vs chemoimmunotherapy (2018) (2018)
2018. Based only on the trials cited in each step. Obinutuzumab was compared with rituximab, each with chemotherapy, and rituximab plus lenalidomide with rituximab plus chemotherapy, in untreated follicular lymphoma.
Text version
  • 2003: Watchful waiting vs immediate chlorambucil
  • 2013: Watchful waiting vs immediate chlorambucil → Bendamustine-rituximab vs R-CHOP
  • 2018: Watchful waiting vs immediate chlorambucil → Bendamustine-rituximab vs R-CHOP → Obinutuzumab vs rituximab, with chemotherapy → Rituximab-lenalidomide vs R-chemotherapy

Reversals and dead ends

Approaches that were abandoned or withdrawn, and trials whose results were later questioned, are part of the story.

  • 1993

    CHOP vs three intensive regimens in advanced lymphoma (1993)

    Single-institution studies had suggested that more intensive chemotherapy might beat CHOP. A trial started by two US cooperative groups, in 899 eligible people with advanced intermediate- or high-grade non-Hodgkin lymphoma, compared CHOP with three such regimens. Three-year survival was 54 in 100 with CHOP and 50 to 52 in 100 with the others, with no significant difference.

    SWOG/ECOG phase III: 1138 registered, 899 eligible, randomised to CHOP, m-BACOD, ProMACE-CytaBOM or MACOP-B. No significant differences in response rates. Three-year alive without disease 41%, 46%, 46%, 41% (P=0.35); 3-year OS 54%, 52%, 50%, 50% (P=0.90), in the order CHOP, m-BACOD, ProMACE-CytaBOM, MACOP-B. Fatal toxic reactions 1%, 5%, 3%, 6% (P=0.09).

  • 2013

    R-CHOP-14 not better than R-CHOP-21 (two randomised trials, 2013)

    Two large randomised trials asked whether giving R-CHOP every two weeks instead of every three helps. A trial in 602 people aged 60 to 80 and a UK trial in 1,080 adults found no survival gain from the two-week schedule. In the UK trial, 2-year survival was 83 in 100 versus 81 in 100.

    Two separate randomised phase 3 trials, not pooled. LNH03-6B (602 patients aged 60-80, aaIPI 1 or more): 3-year EFS 56% (R-CHOP-14) vs 60% (R-CHOP-21), HR 1.04 (95% CI 0.82-1.31; P=0.7614); red-cell transfusion 47% vs 31%. UK trial (1080 adults): 2-year OS 82.7% vs 80.8%, HR 0.90 (0.70-1.15; P=0.3763); 2-year PFS 75.4% vs 74.8% (HR 0.94, 0.76-1.17).

  • 2019

    DA-EPOCH-R not better than R-CHOP: CALGB/Alliance 50303 (2019)

    In a US intergroup trial, 491 eligible adults with previously untreated diffuse large B-cell lymphoma received either R-CHOP or the more intensive infusional regimen DA-EPOCH-R. Progression-free and overall survival did not differ significantly. DA-EPOCH-R was more toxic, with more severe nerve damage (19 in 100 people versus 3 in 100).

    Alliance/CALGB 50303 (phase III, six cycles each): 524 registered, 491 eligible in the final analysis. Median follow-up 5 years: PFS HR 0.93 (95% CI 0.68-1.27; P=.65), 2-year PFS 78.9% (DA-EPOCH-R) vs 75.5% (R-CHOP); OS HR 1.09 (0.75-1.59; P=.64), 2-year OS 86.5% vs 85.7%. Grade 3-4 febrile neutropenia 35.0% vs 17.7%; neuropathy 18.6% vs 3.3%. Treatment-related deaths 2.1% in each arm.

  • 2021

    BELINDA: tisagenlecleucel not superior in second line (2021)

    In this randomised trial of tisagenlecleucel CAR T cells against salvage chemotherapy and transplant as second-line treatment for aggressive lymphoma, event-free survival did not differ: the median was 3 months in both groups. The authors concluded that tisagenlecleucel was not superior to standard salvage therapy.

    BELINDA: randomised phase 3, 322 patients with aggressive B-cell lymphoma refractory to or progressing within 12 months of first-line therapy; tisagenlecleucel (optional bridging) vs salvage chemotherapy and autologous HSCT. Median EFS 3.0 months in both groups; HR 1.07 (95% CI 0.82 to 1.40; P=0.61). Response 46.3% vs 42.5%. Authors: tisagenlecleucel was not superior to standard salvage therapy.

  • 2021

    PI3K inhibitors in FL: accelerated approvals withdrawn (2021-2024)

    Four targeted drugs that block the PI3K protein each received accelerated FDA approval for relapsed follicular lymphoma, from 2014 to 2021. Single-arm studies of each drug had reported response rates in indolent lymphoma. All four follicular lymphoma indications were later withdrawn, between December 2021 and March 2024.

    Single-arm phase 2 studies in relapsed or refractory indolent lymphoma reported: idelalisib (n=125; ORR 57%), copanlisib (n=142; ORR 59%), duvelisib (n=129; FL ORR 42.2%), umbralisib (n=208; ORR 47.1%). Each drug received FDA accelerated approval in relapsed FL. Per the FDA list, the FL indications were withdrawn on 17 December 2021 (duvelisib), 18 February 2022 (idelalisib), 31 May 2022 (umbralisib) and 18 March 2024 (copanlisib).

Today and tomorrow

Standard of care today

Locally advanced

DLBCL, previously untreated. FDA labels read:

  • the current Rituxan prescribing information (DailyMed label version 36, effective 6 January 2025) lists previously untreated CD20-positive DLBCL in combination with CHOP or other anthracycline-based chemotherapy
  • the approval date of that indication was not established. FDA, 19 April 2023 (supplement S-008, BLA 761121): polatuzumab vedotin with R-CHP for adults with previously untreated DLBCL not otherwise specified or high-grade B-cell lymphoma with an International Prognostic Index (IPI) score of 2 or greater, recorded as a regular approval
  • the same supplement converted the 2019 accelerated approval of polatuzumab vedotin with bendamustine and rituximab for relapsed or refractory disease. EMA: the Polivy EPAR page (last updated 20 October 2026) lists Polivy with R-CHP for previously untreated DLBCL among its indications
  • the date of the EU first-line extension was not established. R-CHOP was the control arm in POLARIX (polatuzumab vedotin with R-CHP) and in frontMIND. frontMIND (Lancet 2026) reported better investigator-assessed progression-free survival with tafasitamab and lenalidomide added to R-CHOP in previously untreated high-intermediate-risk or high-risk DLBCL or high-grade B-cell lymphoma, with higher rates of grade 3 or worse and of fatal treatment-emergent adverse events (26 [6%] versus 17 [4%]), fewer deaths overall (82 versus 97) and immature overall survival data (abstract only
  • full text not read)
  • no FDA or EMA action for that combination was read. NCCN B-Cell Lymphomas (Version 4.2026) and the ESMO 2025 Lymphomas guideline are cited by identifier only
  • their text was not read
National Library of Medicine, DailyMed 2025US Food and Drug Administration 2023European Medicines Agency 2026Tilly H, Morschhauser F, Sehn LH, Friedberg JW, Trněný M, Sharman JP, et al 2022Lenz G, Trněný M, Burke JM, Nowakowski GS, Fox CP, Chiappella A, et al 2026Guideline: Zelenetz AD, Gordon LI, Abramson JS, Advani RH, Altahan A, Andreadis B, et al 2026Eyre TA, Cwynarski K, d'Amore F, de Leval L, Dreyling M, Eichenauer DA, et al 2025
Relapsed / refractory

Large B-cell lymphoma (LBCL), second line. FDA actions recorded from the approval letters named in the cited sources:

  • axicabtagene ciloleucel, 1 April 2022 (BL 125643/394), for adults with LBCL refractory to first-line chemoimmunotherapy or relapsing within 12 months of it
  • lisocabtagene maraleucel, 24 June 2022 (BL 125714/90), with two indications, refractory or relapsing within 12 months of first-line chemoimmunotherapy, or refractory or relapsing after first-line chemoimmunotherapy and not eligible for haematopoietic stem cell transplant because of comorbidities or age. Both are recorded as regular approvals. The randomised trials behind these actions are ZUMA-7 and TRANSFORM
  • tisagenlecleucel's second-line trial (BELINDA) is in the timeline, and no second-line tisagenlecleucel FDA action was read. Guideline preferences were not read (NCCN Version 4.2026 and ESMO 2025 cited by identifier only)
FDA 2022FDA 2022Locke FL, Miklos DB, Jacobson CA, Perales MA, Kersten MJ, Oluwole OO, et al 2022Kamdar M, Solomon SR, Arnason J, Johnston PB, Glass B, Bachanova V, et al 2022Bishop MR, Dickinson M, Purtill D, Barba P, Santoro A, Hamad N, et al 2022Guideline: Zelenetz AD, Gordon LI, Abramson JS, Advani RH, Altahan A, Andreadis B, et al 2026Eyre TA, Cwynarski K, d'Amore F, de Leval L, Dreyling M, Eichenauer DA, et al 2025
Relapsed / refractory

LBCL, after two or more lines of systemic therapy. FDA actions recorded from the approval letters named in the cited sources:

  • axicabtagene ciloleucel 18 October 2017, tisagenlecleucel 1 May 2018 and lisocabtagene maraleucel 5 February 2021 (each recorded as a regular approval)
  • polatuzumab vedotin with bendamustine and rituximab, accelerated approval 10 June 2019, converted to regular approval 19 April 2023 (EMA: conditional authorisation 16 January 2020, switched to a full authorisation on 24 May 2022 per the EPAR page)
  • epcoritamab, accelerated approval 19 May 2023
  • glofitamab, accelerated approval 15 June 2023 (EMA: Columvi conditional authorisation 7 July 2023, switched to a standard authorisation 8 May 2025
  • Tepkinly conditional authorisation 22 September 2023). The FDA's list of ongoing accelerated approvals (content current as of 19 October 2026) still shows four DLBCL or LBCL indications: tafasitamab with lenalidomide for people not eligible for autologous stem cell transplant (accelerated approval 31 July 2020
  • letter read), loncastuximab tesirine (23 April 2021
  • letter read), epcoritamab (19 May 2023) and glofitamab (15 June 2023). FDA, 11 February 2025: brentuximab vedotin with lenalidomide and a rituximab product for adults with relapsed or refractory LBCL after two or more lines who are ineligible for autologous haematopoietic stem cell transplant or CAR T-cell therapy (the announcement does not say whether the approval is accelerated or regular). The FDA withdrawn list shows selinexor's DLBCL accelerated approval withdrawn on 30 April 2026. Guideline text was not read
FDA 2017FDA 2018FDA 2021FDA 2019US Food and Drug Administration 2023European Medicines Agency 2026FDA 2023FDA 2023European Medicines Agency 2026European Medicines Agency 2026FDA 2026FDA, Center for Drug Evaluation and Research 2020FDA, Center for Drug Evaluation and Research 2021FDA 2025FDA 2026Guideline: Zelenetz AD, Gordon LI, Abramson JS, Advani RH, Altahan A, Andreadis B, et al 2026Eyre TA, Cwynarski K, d'Amore F, de Leval L, Dreyling M, Eichenauer DA, et al 2025
Locally advanced

Follicular lymphoma, previously untreated. FDA labels read:

  • the current Rituxan prescribing information (version 36, effective 6 January 2025) lists previously untreated follicular CD20-positive B-cell non-Hodgkin lymphoma in combination with first-line chemotherapy and, for those with a complete or partial response, single-agent maintenance, and non-progressing low-grade CD20-positive B-cell non-Hodgkin lymphoma after first-line CVP
  • the approval dates of these indications were not established. Obinutuzumab: FDA, 16 November 2017 (supplement S-017, the new indication
  • S-018 in the same letter updated safety labeling), in combination with chemotherapy followed by obinutuzumab monotherapy in people achieving at least a partial remission, for adults with previously untreated stage II bulky, III or IV follicular lymphoma
  • the letter contains no accelerated-approval wording and the Gazyva label (version 23, effective 1 October 2026) still lists the indication. The Revlimid label read (version 41) lists lenalidomide with a rituximab product for previously treated follicular lymphoma only
  • no first-line lenalidomide-rituximab indication was found in it. The randomised trials in the timeline for this setting include StiL, GALLIUM and RELEVANCE. NCCN B-Cell Lymphomas (Version 4.2026) and the ESMO 2025 Lymphomas guideline are cited by identifier only
  • their text was not read
National Library of Medicine, DailyMed 2025US FDA 2017National Library of Medicine, DailyMed 2026National Library of Medicine, DailyMed 2023Rummel MJ, Niederle N, Maschmeyer G, Banat GA, von Grünhagen U, Losem C, et al 2013Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, et al 2017Morschhauser F, Fowler NH, Feugier P, Bouabdallah R, Tilly H, Palomba ML, et al 2018Guideline: Zelenetz AD, Gordon LI, Abramson JS, Advani RH, Altahan A, Andreadis B, et al 2026Eyre TA, Cwynarski K, d'Amore F, de Leval L, Dreyling M, Eichenauer DA, et al 2025
Relapsed / refractory

Follicular lymphoma, relapsed or refractory. FDA actions read:

  • rituximab, 26 November 1997, for relapsed or refractory low-grade or follicular CD20-positive B-cell non-Hodgkin lymphoma (the letter does not use the term accelerated approval)
  • lenalidomide with a rituximab product for previously treated follicular lymphoma, 28 May 2019 (supplement S-057)
  • tafasitamab with lenalidomide and rituximab for relapsed or refractory follicular lymphoma, 18 June 2025 (supplement S-013
  • no accelerated-approval wording in the letter)
  • epcoritamab with lenalidomide and rituximab as a new indication and single-agent epcoritamab converted to traditional approval, 18 November 2025
  • mosunetuzumab, accelerated approval 22 December 2022
  • axicabtagene ciloleucel, accelerated approval effective 5 March 2021
  • tisagenlecleucel, accelerated approval 27 May 2022
  • lisocabtagene maraleucel, accelerated approval 15 May 2024 converted to traditional approval 20 February 2026. The FDA's list of ongoing accelerated approvals (current as of 19 October 2026) still shows mosunetuzumab, axicabtagene ciloleucel and tisagenlecleucel for follicular lymphoma, and zanubrutinib with obinutuzumab (accelerated approval 7 March 2024
  • the approval letter was not read). The PI3K inhibitors idelalisib, copanlisib, duvelisib and umbralisib and tazemetostat have accelerated approvals listed as withdrawn (see the hooks). EMA: the Lunsumio EPAR page lists a conditional authorisation issued 3 June 2022 for monotherapy after at least two prior systemic therapies
  • the Tepkinly EPAR page (last updated 6 August 2026) lists epcoritamab with lenalidomide and rituximab and epcoritamab monotherapy after two or more lines for follicular lymphoma, and gives a conditional authorisation of 22 September 2023, without dating the follicular indications. Guideline text was not read
US FDA, Center for Biologics Evaluation and Research 1997FDA 2019FDA 2025US FDA 2025US FDA 2022US FDA 2021US FDA 2022US FDA 2024US FDA 2026FDA 2026US Food and Drug Administration 2026FDA 2026EMA 2026European Medicines Agency 2026Guideline: Zelenetz AD, Gordon LI, Abramson JS, Advani RH, Altahan A, Andreadis B, et al 2026Eyre TA, Cwynarski K, d'Amore F, de Leval L, Dreyling M, Eichenauer DA, et al 2025
Any setting
Guidelines. NCCN Guidelines: B-Cell Lymphomas, Version 4.2026 (Zelenetz AD et al., J Natl Compr Canc Netw 2026;24(9), PMID 42753811) and the ESMO Clinical Practice Guideline: Lymphomas (Eyre TA et al., Ann Oncol 2025;36(11):1263-1284, PMID 40774601) are cited by identifier only. Their text was not opened, so no recommendation is attributed to either, and whether these are the current editions was not checked beyond the PubMed records. Subtypes other than DLBCL and follicular lymphoma (primary mediastinal, mantle cell, marginal zone and Burkitt lymphoma) were not researched for this page.
Guideline: Zelenetz AD, Gordon LI, Abramson JS, Advani RH, Altahan A, Andreadis B, et al 2026Eyre TA, Cwynarski K, d'Amore F, de Leval L, Dreyling M, Eichenauer DA, et al 2025

Trials to watch

  • SKYGLO NCT06047080

    In adults with previously untreated large B-cell lymphoma (registry ages 18 to 80), does glofitamab added to polatuzumab vedotin plus R-CHP (Pola-R-CHP) improve progression-free survival, as determined by an independent review facility, compared with Pola-R-CHP alone? Registry record: randomised, open-label phase 3; status active, not recruiting; enrolment 1,130 (actual); estimated primary completion October 2027; no results posted.

  • EPCORE DLBCL-2 NCT05578976

    In adults with newly diagnosed CD20-positive DLBCL (registry ages 18 to 79) planned for six cycles of R-CHOP, does subcutaneous epcoritamab added to R-CHOP differ from R-CHOP in progression-free survival assessed by an independent review committee, for the primary outcome the registry words as participants with an International Prognostic Index (IPI) of 3 to 5? Registry record: randomised, open-label phase 3; status active, not recruiting; enrolment 900 (estimated); estimated primary completion June 2027; no results posted.

  • ZUMA-23 NCT05605899

    In adults with previously untreated high-risk large B-cell lymphoma (registry: IPI score of 4 or 5 at diagnosis, only one cycle of rituximab plus chemotherapy received), does first-line axicabtagene ciloleucel improve event-free survival, by blinded central assessment, compared with the investigator's choice of standard therapy (R-CHOP or DA-EPOCH-R, as the arm description lists)? Registry record: randomised, open-label, adaptive phase 3; status active, not recruiting; enrolment 300 (estimated); estimated primary completion March 2031; no results posted.

  • ESCALADE NCT04529772

    In adults aged 75 or younger with previously untreated non-germinal-centre DLBCL, does acalabrutinib added to R-CHOP improve progression-free survival (Lugano classification) compared with placebo plus R-CHOP? Registry record: randomised, double-blind, placebo-controlled phase 3; status active, not recruiting; enrolment 611 (actual); estimated primary completion February 2027; no results posted.

  • EPCORE FL-2 NCT06191744

    In adults with previously untreated follicular lymphoma, does subcutaneous epcoritamab with rituximab and lenalidomide (R2) differ from chemoimmunotherapy (obinutuzumab or rituximab with CHOP or bendamustine) in complete response at 30 months and in progression-free survival (the two primary outcomes listed for arm A1 against arm B)? The registry also lists a shorter-duration epcoritamab arm and an R2 arm. Registry record: randomised, open-label phase 3; status active, not recruiting; enrolment 1,095 (actual); estimated primary completion November 2037; no results posted.

  • MorningLyte NCT06284122

    In adults with previously untreated follicular lymphoma with FLIPI 2 to 5, does mosunetuzumab plus lenalidomide improve progression-free survival assessed by an independent review committee compared with an anti-CD20 antibody plus chemotherapy (R-CHOP, G-CHOP, R-bendamustine or G-bendamustine, as the arms list)? Registry record: randomised, open-label phase 3; status active, not recruiting; enrolment 790 (estimated); estimated primary completion November 2028; no results posted.

References

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2017UnderstandingChemotherapy

majorRelapsed / refractoryNeeds review

SCHOLAR-1: outcomes in refractory DLBCL (2017)

A pooled look back at people whose diffuse large B-cell lymphoma was refractory to treatment found that about one in four responded to the next treatment and a fifth were alive at two years. It combined data from two trials and two hospital cohorts, and is not a treatment trial.

SCHOLAR-1: retrospective patient-level pooling of two phase 3 trials (CORAL, LY.12) and two observational cohorts; 861 patients, 636 meeting refractory-disease criteria. Objective response to the next line of therapy 26% (CR 7%); median OS 6.3 months from the start of salvage therapy; 20% alive at 2 years. Outcomes were reported as consistently poor across subgroups and cohorts.

Standard before

The abstract states that published analyses of large-scale outcome data in refractory DLBCL were limited.

Why it mattered

SCHOLAR-1 described response and survival in refractory DLBCL using pooled patient-level data, and was later used as the comparator in a published propensity-scored comparison with the 2-year ZUMA-1 data; the authors of that comparison note it was a nonrandomised analysis.

Caveats

  • Retrospective pooled analysis of trial and observational cohorts: not a treatment comparison and not a trial result; the numbers describe outcomes of whatever next-line therapy was given.
  • The definition of refractory disease is specific to SCHOLAR-1 (progressive or stable disease as best response during chemotherapy, or relapse within 12 months of autologous stem-cell transplantation); other refractory populations (for example in ZUMA-7 or BELINDA) are defined differently.
  • Response and survival are measured from the start of salvage therapy for refractory disease, which is not the same landmark as the CAR T trials' enrolment or infusion.
  • Response was evaluable in 523 and survival in 603 of the 636 patients meeting the refractory-disease criteria; the response and survival figures above are pooled across the four cohorts.