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Bone marrow and blood (plasma cell malignancy)

Multiple myeloma

A history of multiple myeloma treatment: alkylators, transplant, novel agents, antibodies and T-cell therapies.

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

26.11%→65.92%

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 October 1845 a 45-year-old tradesman came under the care of William Macintyre, a physician in London, with pain in the chest, back and loins. Nitric acid first cleared his urine, which later set into a yellow mass that dissolved on heating; Henry Bence Jones, who was analysing urine, met Macintyre in consultation. Bence Jones's paper was read to the Royal Society on 22 April 1847 and printed in 1848, and Macintyre's own report followed in 1850; it does not use the word myeloma. Earlier cases of mollities ossium, including Solly's in 1844, are cited in the same texts, so these are cases described in the 1840s, not first cases.
  • On the SEER Cancer Stat Facts page for myeloma, observed five-year relative survival in the SEER 8 series is 26.11% for 1975, 34.41% for 2000, 55.10% for 2010 and 65.92% for 2018. The US age-adjusted death rate, a separate series, is 2.93 per 100,000 in 1975, 3.98 in 1995 (the highest value in the table) and 2.56 in 2024. These are different series, and the page does not say how much of the change reflects treatment, diagnostic practice or other factors.
  • Belantamab mafodotin (Blenrep) received FDA accelerated approval on 5 August 2020. A Federal Register notice records that the confirmatory DREAMM-3 trial did not meet its primary endpoint of superior progression-free survival, that the sponsor asked in writing on 18 November 2022 for the licence to be revoked, and that it was revoked as of 6 February 2023. In the EU the conditional authorisation of 25 August 2020 was not renewed (decision of 23 February 2024). New authorisations followed in the EU on 23 July 2025 and from FDA on 23 October 2025, the latter with bortezomib and dexamethasone after at least two prior lines of therapy including a proteasome inhibitor and an immunomodulatory agent.

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

Anatomists & surgeons

  1. 1844 · Origin · UnderstandingMollities ossium cases of the 1840s: Solly, Macintyre, Bence JonesIn the 1840s doctors described patients whose bones had softened and broke easily, then called mollities ossium. In one man, seen from October 1845, the urine reacted oddly to nitric acid and heat, and microscopy of his bones showed soft, cell-filled material. The urinary protein was later named after Henry Bence Jones and is linked today with myeloma.Solly (1844) published cases of mollities ossium. Macintyre (1850) described a 45-year-old man first seen on 30 October 1845 with bone pain and urine rich in albumin-like animal matter that behaved atypically with nitric acid and heat; at autopsy the ribs were soft and brittle. Dalrymple (1846) examined a rib and two lumbar vertebrae. Bence Jones's urine paper was read in April 1847 and printed in 1848. Macintyre's text does not use the word myeloma.

Chemotherapy

  1. 1962 · Treatment · Chemotherapy⚑ needs reviewMelphalan, then melphalan plus prednisone, in myelomaMelphalan was evaluated in myeloma in 1962. A 1969 report on 183 people treated with melphalan found that those given melphalan with prednisone responded more often than those given melphalan alone, and their median survival was about six months longer. A 1998 overview found no difference in deaths between combination chemotherapy and melphalan plus prednisone.Alexanian 1969, publisher abstract: 183 patients treated with melphalan, objective response 43%; among evaluable patients 70% responded to melphalan plus prednisone, 35% to intermittent melphalan and 19% to daily melphalan; median survival with melphalan-prednisone was about six months longer than with melphalan alone. Bergsagel 1962: evaluation of L-phenylalanine mustard in myeloma (title only). Myeloma Trialists' overview (6,633 patients, 27 trials): response 60.0% versus 53.2% for combination chemotherapy versus MP; no mortality difference (P=0.6).
  2. 1975 · Understanding · UnderstandingDurie-Salmon clinical staging system (1975)In 1975 Durie and Salmon described a staging system for multiple myeloma built on an estimate of how many myeloma cells a person carried. It combined the extent of bone damage, haemoglobin, calcium and the level of abnormal antibody protein in blood and urine, and it tracked with response to treatment and survival.In 71 patients, myeloma cell mass, calculated from monoclonal immunoglobulin synthesis and metabolism, was predicted by the extent of bone lesions, haemoglobin, serum calcium and serum and urine M-component. Cell mass correlated significantly with response to chemotherapy and survival. The authors synthesised the results into a clinical staging system with three tumour cell mass levels.

Molecular origins

  1. 1996 · Treatment · Cell therapy & transplantAutologous transplantation trials: IFM 90, MRC VII, IFM 94Three randomised trials tested high-dose treatment followed by return of a person's own blood-forming cells. Two compared it with conventional chemotherapy and found more responses and longer survival with the high-dose approach. A third found that two transplants in a row gave longer survival than one.IFM 90 (n=200, age under 65): 5-year EFS 28% versus 10% (P=0.01) and 5-year survival 52% versus 12% (P=0.03), high-dose therapy with autologous BMT versus conventional chemotherapy. MRC Myeloma VII (n=407, under 65): median survival 54.1 versus 42.3 months (P=0.04, intention to treat). IFM 94 (n=399, under 60): 7-year survival 42% versus 21% (P=0.01), double versus single transplant.

Targeted therapy

  1. 1999 · Treatment · TargetedThalidomide shows activity in refractory myelomaThalidomide, a drug that decades earlier had caused severe birth defects when given in pregnancy, was tested in 84 people whose myeloma had not responded to treatment. About one in three had their myeloma protein fall by at least a quarter. Later randomised trials tested it in newly diagnosed myeloma, and the FDA approved it for that use in 2006.Single-arm study (n=84, previously treated, refractory myeloma; oral thalidomide 200 to 800 mg daily): response 32% (paraprotein reduction of at least 25%, lasting at least six weeks); 12-month Kaplan-Meier event-free survival 22% and overall survival 58%. Later randomised trials: IFM 99-06, MPT versus MP, median OS 51.6 versus 33.2 months (HR 0.59); thalidomide-dexamethasone versus placebo-dexamethasone, median TTP 22.6 versus 6.5 months (P<0.001).
  2. 2003 · Treatment · TargetedBortezomib in relapsed myeloma: SUMMIT phase 2 to APEXBortezomib, an injected proteasome inhibitor, was tested in a phase 2 study of people whose myeloma had returned and was not responding to their last treatment. About one in three responded. A later randomised trial found longer time to progression and better survival than high-dose dexamethasone. The FDA gave accelerated approval in 2003; a 2005 supplement fulfilled the commitments.SUMMIT (phase 2, n=202, refractory to last therapy): response 35% in 193 evaluable patients; median OS 16 months; median duration of response 12 months. APEX (phase 3, relapse after 1 to 3 prior therapies): bortezomib versus high-dose dexamethasone, median TTP (primary endpoint) 6.22 versus 3.49 months (HR 0.55; P<0.001); CR+PR 38% versus 18%; OS HR 0.57 (P=0.001), crossover permitted. FDA accelerated approval 13 May 2003; supplement S-006 25 March 2005 fulfilled the 21 CFR 314.510 commitments.
  3. 2005 · Understanding · UnderstandingISS, R-ISS and R2-ISS: myeloma risk staging (2005-2022)Myeloma staging moved from tumour-mass estimates to simple blood tests in 2005, when the International Staging System grouped patients into three stages by two blood values. In 2015 and 2022 further versions added chromosome changes and other markers, giving four risk groups in the latest. Survival differed clearly between the groups in each report.ISS (2005; 10,750 previously untreated symptomatic patients): stage I (serum β2-microglobulin <3.5 mg/L, albumin ≥3.5 g/dL) median survival 62 months; stage III (β2-microglobulin ≥5.5 mg/L) 29 months. R-ISS (2015; 3,060 patients with complete data) added high-risk cytogenetics or high LDH: 5-year OS 82%, 62%, 40% for stages I to III. R2-ISS (2022; additive score including 1q gain) defines four groups: median OS not reached, 109.2, 68.5, 37.9 months.
  4. 2006 · Treatment · TargetedLenalidomide plus dexamethasone in relapsed myeloma: MM-009, MM-010Lenalidomide is an oral drug related to thalidomide. Two placebo-controlled trials added it to high-dose dexamethasone in people who had received at least one earlier treatment for myeloma. In both, the disease took longer to progress and more people responded, and survival was longer. Low blood counts and blood clots were more common with lenalidomide.Two phase 3 trials, lenalidomide 25 mg plus dexamethasone versus placebo plus dexamethasone, after at least one prior therapy. MM-009 (n=353): median TTP 11.1 versus 4.7 months, median OS 29.6 versus 20.2 months (P<0.001 for both). MM-010 (n=351): median TTP (primary endpoint) 11.3 versus 4.7 months (P<0.001); OS HR 0.66 (P=0.03). Grade 3 or 4 neutropenia 41.2% versus 4.6% and venous thromboembolism 14.7% versus 3.4% (MM-009).
  5. 2008 · Treatment · TargetedVISTA: bortezomib added to melphalan-prednisone, first lineIn people with newly diagnosed myeloma who could not have high-dose therapy, adding bortezomib to melphalan and prednisone lengthened the time before the disease progressed and raised the proportion who responded. An updated report found longer survival with the bortezomib combination. Nerve problems were reported, and most improved.Phase 3, n=682, previously untreated and ineligible for high-dose therapy: VMP versus MP, nine 6-week cycles. Median time to progression (primary endpoint) 24.0 versus 16.6 months (HR 0.48; P<0.001); partial response or better 71% versus 35%; complete response 30% versus 4%. Updated analysis, median follow-up 36.7 months: OS HR 0.653 (P<0.001); 3-year OS 68.5% versus 54.0%.

Immunotherapy

  1. 2012 · Treatment · TargetedCarfilzomib: accelerated approval to ASPIRE and ENDEAVORCarfilzomib is a proteasome inhibitor given by infusion. After a single-agent study in heavily treated myeloma, the US granted accelerated approval in 2012, pending confirmatory trials. Two randomised trials, one adding it to lenalidomide and dexamethasone and one comparing it with bortezomib, found longer time without progression; the single-agent approval was later made regular.PX-171-003-A1 (single-arm phase 2, 257 evaluable for efficacy): ORR 23.7%, median DOR 7.8 months, median OS 15.6 months. ASPIRE (KRd versus Rd, n=792): median PFS 26.3 versus 17.6 months, HR 0.69 (95% CI 0.57 to 0.83); 24-month OS 73.3% versus 65.0%. ENDEAVOR (Kd versus Vd, n=929): median PFS 18.7 versus 9.4 months, HR 0.53 (0.44 to 0.65). Interim analyses. FDA accelerated approval 2012; monotherapy converted 2016.
  2. 2012 · Treatment · TargetedLenalidomide maintenance after autologous transplantAfter a stem cell transplant, people with myeloma were randomly given lenalidomide or placebo until the disease progressed. In two trials, progression took longer with lenalidomide, but second cancers were more frequent. One trial reported fewer deaths with lenalidomide; the other found similar survival at four years. A pooled analysis of three trials reported longer survival.IFM 2005-02 (n=614, age under 65): median PFS (primary) 41 versus 23 months, HR 0.50 (P<0.001); second primary cancers 3.1 versus 1.2 per 100 patient-years. CALGB 100104 (n=460, under 71): median time to progression 46 versus 27 months (P<0.001); deaths 15% versus 23% (P=0.03). Patient-level meta-analysis of three trials (n=1,208): median PFS 52.8 versus 23.5 months (HR 0.48); OS HR 0.75 (95% CI 0.63 to 0.90). FDA maintenance indication 22 February 2017.
  3. 2013 · Treatment · ImmunotherapyTreating smouldering myeloma: from lenalidomide to daratumumabSmouldering myeloma is an early stage without symptoms, usually managed by watching. Three randomised trials compared early treatment with watching: lenalidomide-based treatment (reported in 2013 and 2019) and daratumumab (2024). Each reported a longer time before the disease progressed with treatment. In November 2025 the US regulator approved daratumumab for adults with high-risk smouldering myeloma.Three randomised trials, each reported separately. QuiRedex (n = 119; lenalidomide-dexamethasone vs observation): TTP HR 0.18 (95% CI 0.09-0.32). E3A06 (n = 182; lenalidomide vs observation): PFS HR 0.28 (0.12-0.62). AQUILA (n = 390; SC daratumumab vs active monitoring): PFS HR 0.49 (0.36-0.67), 5-year PFS 63.1% vs 40.8%, OS HR 0.52 (0.27-0.98). FDA approved daratumumab monotherapy for high-risk smouldering myeloma on 6 November 2025.
  4. 2014 · Understanding · Understanding⚑ needs reviewIMWG 2014 criteria: biomarkers join CRAB to define myelomaIn 2014 an international expert group changed the definition of myeloma. Besides organ damage, three laboratory or imaging markers could now identify people very likely to develop that damage, so they could be called myeloma, and offered treatment, earlier. Some people previously labelled smouldering myeloma were reclassified.IMWG consensus (Rajkumar 2014) added validated biomarkers to the CRAB features (hypercalcaemia, renal failure, anaemia, bone lesions) in the myeloma definition, for patients otherwise classed as smouldering. A 2023 meta-analysis (Ludwig) describes them as ≥60% bone marrow plasma cells, free light chain ratio ≥100 and >1 MRI focal lesion of ≥5 mm. No trial data are reported in the consensus.
  5. 2014 · Treatment · TargetedFIRST and SWOG S0777: lenalidomide-based first-line treatmentTwo trials in newly diagnosed myeloma without immediate transplant tested lenalidomide-based treatment. In FIRST, continuous lenalidomide with dexamethasone gave longer progression-free survival than melphalan, prednisone and thalidomide. In SWOG S0777, adding bortezomib to lenalidomide and dexamethasone gave longer progression-free and overall survival. Each trial has its own comparison.FIRST (n=1623): continuous lenalidomide-dexamethasone versus MPT, median PFS 25.5 versus 21.2 months (HR 0.72; P<0.001); final analysis median OS 59.1 versus 49.1 months (HR 0.78; 95% CI 0.67 to 0.92). SWOG S0777 (n=525): VRd versus Rd, median PFS 43 versus 30 months (HR 0.712, 96% CI 0.56 to 0.906), median OS 75 versus 64 months (HR 0.709; 95% CI 0.524 to 0.959).
  6. 2015 · Treatment · ImmunotherapyDaratumumab: anti-CD38 antibody from single agent to CASTOR/POLLUXDaratumumab is an antibody against CD38, a protein on myeloma cells. Alone, it shrank myeloma in some heavily treated people, and the US approved it in 2015. In 2016, two large trials added it to standard two-drug regimens at relapse; in each, the risk of progression or death fell by about three-fifths.Single-agent daratumumab 16 mg/kg: ORR 36% (GEN501, phase 1-2) and 29.2% (SIRIUS, phase 2). Relapsed myeloma, randomised phase 3, interim PFS (primary): CASTOR, Dvd versus Vd (n=498), HR 0.39 (95% CI 0.28 to 0.53); POLLUX, DRd versus Rd (n=569), HR 0.37 (0.27 to 0.52); both P<0.001. The FDA accelerated approval (2015) was followed by supplements in 2016 that fulfilled its commitments.
  7. 2016 · Understanding · UnderstandingMinimal residual disease: IMWG criteria to an ODAC endpoint voteIn 2016 myeloma experts defined response categories deeper than complete response, based on searching the bone marrow for remaining cancer cells. A 2017 pooled analysis linked a negative result with longer survival. In April 2024 an advisory committee to the US drug regulator voted unanimously that this test can serve as an endpoint for accelerated approval.IMWG consensus (Kumar 2016) defined MRD-negative response categories, with or without imaging-based absence of extramedullary disease. A meta-analysis (Munshi 2017) found MRD negativity associated with longer PFS (14 studies, n = 1273; HR 0.41, 95% CI 0.36-0.48) and OS (12 studies, n = 1100; HR 0.57, 0.46-0.71). On 12 April 2024 FDA's ODAC voted 12 to 0 that evidence supports MRD as an accelerated approval endpoint; a draft FDA guidance followed in January 2026.
  8. 2017 · Treatment · ImmunotherapyDaratumumab first line without transplant: ALCYONE, MAIA, CEPHEUSThree trials added the CD38 antibody daratumumab to regimens for people with newly diagnosed myeloma who were not having an immediate transplant. Each reported a lower risk of progression or a higher rate of undetectable residual disease than the same regimen without it. Severe infections or pneumonia were more frequent with daratumumab in two of the trials.Added to VMP (ALCYONE, n=706): 18-month PFS 71.6% versus 50.2%, HR 0.50 (95% CI 0.38 to 0.65). Added to Rd (MAIA, n=737): 30-month PFS 70.6% versus 55.6%, HR 0.56; at 64.5 months median PFS 61.9 versus 34.4 months and OS HR 0.66 (0.53 to 0.83). Added to VRd (CEPHEUS, n=395; primary end point MRD negativity): 60.9% versus 39.4%; PFS HR 0.57 (0.41 to 0.79). Controls and primary end points differ.
  9. 2017 · Treatment · Cell therapy & transplantTransplant with RVD or RVD alone: IFM 2009 and DETERMINATIONTwo randomised trials asked whether people with newly diagnosed myeloma needed high-dose therapy with a stem cell transplant on top of a three-drug combination. Progression-free survival was longer with transplant in both. Overall survival was not significantly different at about four to five years. Side effects such as low white-cell counts were more common with transplant.IFM 2009 (n=700; RVD alone versus RVD plus high-dose melphalan and transplant; lenalidomide maintenance for 1 year): median PFS 36 versus 50 months (adjusted HR 0.65; P<0.001); OS at 4 years 82% versus 81%. DETERMINATION (357 RVD alone versus 365 transplantation; lenalidomide until progression): median PFS 46.2 versus 67.5 months (HR 1.53, RVD alone versus transplantation; 95% CI 1.23 to 1.91); 5-year survival 79.2% versus 80.7% (HR for death 1.10; 95% CI 0.73 to 1.65).
  10. 2019 · Treatment · ImmunotherapyQuadruplet induction before transplant: CASSIOPEIA, GRIFFIN, PERSEUSIn people with newly diagnosed myeloma who could have a stem-cell transplant, three trials added daratumumab to the multi-drug regimens given before and after transplant. The proportion with the deepest responses rose in each, and the trial with progression as its main outcome found a lower risk of progression or death.Daratumumab added around ASCT. CASSIOPEIA (D-VTd, n=1085): sCR at day 100 29% versus 20%, OR 1.60 (95% CI 1.21 to 2.12). GRIFFIN (D-RVd, n=207, registered phase 2): sCR 42.4% versus 32.0% at the primary analysis. PERSEUS (D-VRd, n=709): 48-month PFS 84.3% versus 67.7%, HR 0.42 (0.30 to 0.59); MRD negativity 75.2% versus 47.5%.
  11. 2019 · Treatment · ImmunotherapyIsatuximab: ICARIA-MM, IKEMA, HD7 and IMROZIsatuximab is a second antibody against CD38. Added to pomalidomide or carfilzomib regimens at relapse, it lengthened time without progression. In newly diagnosed myeloma it raised the share with undetectable residual disease before transplant and, in people not having a transplant, lowered the risk of progression or death.Isatuximab, randomised phase 3. ICARIA-MM (Isa-Pd versus Pd, n=307): median PFS 11.5 versus 6.5 months, HR 0.596 (95% CI 0.44 to 0.81). IKEMA (Isa-Kd versus Kd, n=302): HR 0.53 (99% CI 0.32 to 0.89). GMMG-HD7 part 1 (n=660): MRD negativity after induction 50% versus 36%. IMROZ (Isa-VRd versus VRd, n=446): 60-month PFS 63.2% versus 45.2%, HR 0.60 (98.5% CI 0.41 to 0.88).

Precision & engineered

  1. 2020 · Reversal · TargetedVenetoclax in myeloma: BELLINI signals harm, CANOVA misses PFSVenetoclax blocks BCL-2, a protein that helps some myeloma cells survive. In an unselected group with relapsed myeloma, adding it to bortezomib and dexamethasone delayed progression but was followed by more deaths, mostly from infection. A later trial in people whose myeloma has a t(11;14) change did not reach its progression-free survival goal.BELLINI (venetoclax or placebo plus Vd, n=291): median PFS 22.4 versus 11.5 months, HR 0.63 (95% CI 0.44 to 0.90); eight fatal infections with venetoclax, none with placebo. Final analysis at 45.6 months: OS HR 1.19 (0.80 to 1.77; P=0.39). CANOVA (venetoclax-dexamethasone versus Pd, t(11;14)-positive, n=263): median PFS 9.9 versus 5.8 months, HR 0.823 (0.596 to 1.136; P=0.24), primary end point not met; OS HR 0.856 (0.612 to 1.197).
  2. 2021 · Treatment · Cell therapy & transplantBCMA CAR T cells: ide-cel and cilta-cel, from KarMMa to CARTITUDE-4CAR T-cell therapy takes a person's own T cells, equips them to recognise BCMA on myeloma cells, and returns them as a single infusion. Single-arm studies reported responses in most heavily treated people. Later randomised trials, at earlier relapse, found longer time without progression than standard regimens, and one has reported longer survival.Single-arm: KarMMa (n=128 treated) ORR 73%; CARTITUDE-1 (n=97) ORR 97%. Randomised phase 3, PFS primary: KarMMa-3, ide-cel versus standard regimens (n=386), median 13.3 versus 4.4 months, HR 0.49 (95% CI 0.38 to 0.65); CARTITUDE-4, cilta-cel versus PVd or DPd (n=419), HR 0.26 (0.18 to 0.38). CARTITUDE-4 update at 33.6 months: PFS HR 0.29 (0.22 to 0.39); OS HR 0.55 (0.39 to 0.79).
  3. 2022 · Treatment · ImmunotherapyBispecifics: teclistamab, talquetamab, elranatamab, linvoseltamabBispecific antibodies hold a T cell and a myeloma cell together so the T cell can attack. Teclistamab, elranatamab and linvoseltamab target BCMA; talquetamab targets GPRC5D. In single-arm studies of heavily treated people, about half to nearly three-quarters responded. The US approved all four between 2022 and 2025.Single-arm studies. MajesTEC-1 (teclistamab, n=165; ORR primary): ORR 63.0%, median PFS 11.3 months. MagnetisMM-3 cohort A (elranatamab, n=123; ORR primary): 61.0%. LINKER-MM1 (linvoseltamab, phase I/II): 71% at 200 mg, 48% at 50 mg. MonumenTAL-1 (talquetamab) is the phase 1 report: 70% and 64% at two subcutaneous doses. Cytokine release syndrome: 72.1% with teclistamab, 57.7% with elranatamab. FDA accelerated approvals 2022 to 2025; teclistamab converted in 2026.
  4. 2023 · Reversal · Antibody–drug conjugateBelantamab mafodotin: withdrawn in 2023, approved again in 2025Belantamab mafodotin, an antibody-drug conjugate aimed at BCMA, was approved in the US in 2020 on response rates. Its required follow-up trial did not show longer time without progression than pomalidomide and dexamethasone, and the US licence was withdrawn in 2023. Two later trials of combinations reported longer progression-free survival, and the US approved a combination in 2025.DREAMM-2 (randomised phase 2, n=196): ORR 31% (2.5 mg/kg) and 34% (3.4 mg/kg). DREAMM-3 (versus Pd, n=325), primary analysis: median PFS 11.2 versus 7.0 months, HR 1.03 (95% CI 0.72 to 1.47), P=0.56; final analysis PFS HR 0.87 (0.64 to 1.18), OS HR 0.98 (0.73 to 1.30). DREAMM-7 (BVd versus DVd): PFS HR 0.41 (0.31 to 0.53). DREAMM-8 (BPd versus PVd): HR 0.52 (0.37 to 0.73). Ocular events 79% and 89%.
  5. 2025 · Treatment · ImmunotherapyBispecifics move earlier: MajesTEC-3, MajesTEC-9, MonumenTAL-3Three randomised trials tested bispecific antibodies after only one to three earlier treatments. Teclistamab with daratumumab, teclistamab alone, and talquetamab with daratumumab each lowered the risk of progression or death compared with standard regimens. Serious side effects were more frequent with the teclistamab regimens, including severe infections in the teclistamab-alone trial.Randomised phase 3, PFS primary. MajesTEC-3 (teclistamab-daratumumab versus DPd or DVd, n=587): 36-month PFS 83.4% versus 29.7%, HR 0.17 (95% CI 0.12 to 0.23). MajesTEC-9 (teclistamab versus PVd or Kd, n=593): 18-month PFS 69.8% versus 26.9%, HR 0.29 (0.23 to 0.38); OS HR 0.60 (0.43 to 0.83). MonumenTAL-3 (n=864): Tal-DP versus DPd HR 0.28 (0.20 to 0.40); Tal-D versus DPd HR 0.33 (0.24 to 0.46).
  6. 2026 · De-escalation · TargetedENDURANCE: continuous or fixed-duration lenalidomideIn people with standard-risk newly diagnosed myeloma who did not have an up-front transplant, lenalidomide maintenance for two years was compared with maintenance until progression. Overall survival at seven years was about 69 percent in both groups. Serious non-blood side effects and second cancers were less frequent with the two-year course.ENDURANCE (E1A11), standard-risk newly diagnosed myeloma without up-front ASCT; second randomisation after proteasome inhibitor-lenalidomide induction: indefinite (n=260) versus 2-year (n=256) lenalidomide. Primary endpoint OS: 7-year OS 68.6% versus 69.0% (difference -0.4 points; 95% CI -9.0 to 8.3; P=0.93), median follow-up 86 months. 7-year PFS 36.1% versus 29.7% (difference 6.4 points; 95% CI -2.6 to 15.4). Grade 3 or higher nonhematologic events 48.2% versus 31.5%.

Then and now

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

    • 26.11%

      1975 (observed value; first year in the table)

    People with myeloma, all races, both sexes (chart note); the SEER 8 five-year relative survival series (1975-2018) on the SEER Cancer Stat Facts myeloma page. The page states no age range, risk group or treatment status for this series.

    Relative survival excludes deaths from other causes. 'Observed' is the table's label for the yearly value, as opposed to the Joinpoint modeled-trend value in the adjacent column. The column is headed 'Year' and the chart note says only 'SEER 8 5-Year Relative Survival Percent from 1975-2018'; the page does not say the year is the year of diagnosis. SEER 8 covers a limited set of registries, and single-year values fluctuate (for example 22.79% in 1976 and 26.54% in 1978 in the same series). Survival measured from diagnosis can change through changes in diagnostic practice, case mix and treatment, and the page does not apportion the change in this series between them; read it beside the mortality values. Compare only with other values from this same SEER 8 series, not with the SEER 21 values. The modeled-trend value for 1975 is 24.95%.

    Source

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

    • 34.41%

      2000 (observed value)

    Same series as above: all races, both sexes, SEER 8, five-year relative survival.

    Single-year observed value (modeled trend for 2000: 37.18%). Shown because it precedes the 2003 FDA approval of bortezomib in this timeline; the page does not link any value to a treatment. Relative survival excludes deaths from other causes. 'Observed' is the table's label for the yearly value, as opposed to the Joinpoint modeled-trend value in the adjacent column. The column is headed 'Year' and the chart note says only 'SEER 8 5-Year Relative Survival Percent from 1975-2018'; the page does not say the year is the year of diagnosis. SEER 8 covers a limited set of registries, and single-year values fluctuate (for example 22.79% in 1976 and 26.54% in 1978 in the same series). Survival measured from diagnosis can change through changes in diagnostic practice, case mix and treatment, and the page does not apportion the change in this series between them; read it beside the mortality values. Compare only with other values from this same SEER 8 series, not with the SEER 21 values.

    Source

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

    • 55.1%

      2010 (observed value)

    Same series as above: all races, both sexes, SEER 8, five-year relative survival.

    Single-year observed value (modeled trend for 2010: 53.28%). Treatment, diagnostic criteria and age structure changed over these years and the page apportions the rise to none of them: the value cannot be read as the effect of one drug or strategy. Relative survival excludes deaths from other causes. 'Observed' is the table's label for the yearly value, as opposed to the Joinpoint modeled-trend value in the adjacent column. The column is headed 'Year' and the chart note says only 'SEER 8 5-Year Relative Survival Percent from 1975-2018'; the page does not say the year is the year of diagnosis. SEER 8 covers a limited set of registries, and single-year values fluctuate (for example 22.79% in 1976 and 26.54% in 1978 in the same series). Survival measured from diagnosis can change through changes in diagnostic practice, case mix and treatment, and the page does not apportion the change in this series between them; read it beside the mortality values. Compare only with other values from this same SEER 8 series, not with the SEER 21 values.

    Source

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

    • 65.92%

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

    Same series as above: all races, both sexes, SEER 8, five-year relative survival.

    Observed single-year value (modeled trend for 2018: 64.49%). The entries for 2019-2023 in the table are modeled-trend values only (65.75% to 70.47%) and are not used. Most people in this cohort were diagnosed before the antibody-based first-line regimens, CAR T-cell products and bispecific antibodies listed in the timeline were approved. Relative survival excludes deaths from other causes. 'Observed' is the table's label for the yearly value, as opposed to the Joinpoint modeled-trend value in the adjacent column. The column is headed 'Year' and the chart note says only 'SEER 8 5-Year Relative Survival Percent from 1975-2018'; the page does not say the year is the year of diagnosis. SEER 8 covers a limited set of registries, and single-year values fluctuate (for example 22.79% in 1976 and 26.54% in 1978 in the same series). Survival measured from diagnosis can change through changes in diagnostic practice, case mix and treatment, and the page does not apportion the change in this series between them; read it beside the mortality values. Compare only with other values from this same SEER 8 series, not with the SEER 21 values.

    Source

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

    • 63.7%

      2016-2022

    People with myeloma, all races, both sexes, all stages together; the headline figure on the SEER Cancer Stat Facts myeloma page. The page states no age range beside the figure; median age at diagnosis on the same page is 69 (SEER 21, 2019-2023).

    A different registry set and a multi-year period from the SEER 8 series above, so it is not a continuation of that series and must not be subtracted from it. The page labels the period '2016-2022' and does not say whether it is the diagnosis period. Relative survival, with the same diagnostic-practice and case-mix limits as above.

    Source

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

    • 63%

      2016-2022; distant stage at diagnosis (96% of cases)

    People with myeloma, all races, both sexes; distant (cancer has metastasized) by SEER Combined Summary Stage.

    Stage-specific value from the same SEER 21 table as the 63.7% figure. The page gives the stage mix as 3% localized (82.1% five-year relative survival; the page text gives 3.3%), 0% regional (80.7%), 96% distant (63.0%) and 0% unstaged (69.0%). The page uses SEER Combined Summary Stage categories and does not mention the myeloma-specific staging systems (ISS, R-ISS, R2-ISS) described in the timeline. Not comparable with SEER 8 values.

    Source

  • Age-standardised mortality · United States

    • 2.93per 100,000

      1975 (observed value; first year in the table)

    Deaths from myeloma, all races, both sexes, age-adjusted; the page labels the series 'U.S. Mortality' and states that deaths come from U.S. Mortality, not SEER registries.

    Death rates describe the whole US population and are not measured from the date of diagnosis, so they are shown beside survival. The standard population is not described on the page. The page attributes no change in this series to a cause. The modeled-trend value for 1975 is 3.04.

    Source

  • Age-standardised mortality · United States

    • 3.98per 100,000

      1995 (observed value; highest value in the table)

    Same series as above: age-adjusted U.S. death rate for myeloma, all races, both sexes.

    Highest observed value in the table (3.97 in 1994, 3.91 in 1996). The rate rose from 2.93 in 1975 before it fell, while observed five-year relative survival in SEER 8 was 34.00% for 1995 (modeled trend 32.68%): the two series answer different questions and are not combined. Same limits as the 1975 value.

    Source

  • Age-standardised mortality · United States

    • 3.32per 100,000

      2010 (observed value)

    Same series as above: age-adjusted U.S. death rate for myeloma, all races, both sexes.

    Intermediate point (observed values 3.29 in 2009 and 3.39 in 2011). Same limits as the 1975 value.

    Source

  • Age-standardised mortality · United States

    • 2.56per 100,000

      2024 (observed value; last year in the table)

    Same series as above: age-adjusted U.S. death rate for myeloma, all races, both sexes.

    The page headline gives 2.8 per 100,000 for 2020-2024 deaths; use one or the other, not both. The page states that age-adjusted death rates fell on average 3.0% a year over 2015-2024 and that rates of new cases were stable over 2014-2023, and attributes neither pattern to a cause. A falling death rate and a rising survival percentage answer different questions. The modeled-trend value for 2024 is 2.54.

    Source

  • 10-year relative survival · United Kingdom

    • 9.3%

      1970s (as labelled on the page)

    People diagnosed with myeloma in the UK; the Cancer Research UK page states that around 1 in 10 (9.3%) survived beyond ten years in the 1970s. Age range and the exact diagnosis period are not stated beside the figure.

    The page does not name the measure (net, relative or observed survival) or the age standardisation, and the metric label is the nearest available. The 1970s sentence does not itself name the UK; the page's other statistics and its 2018 sentence do, and the figure is read as UK data on that basis. The page states that survival trends reflect a combination of changes in treatment and stage distribution, which themselves vary by age, sex and deprivation. Not comparable with the US SEER series.

    Source

  • 10-year relative survival · United Kingdom

    • 37.8%

      2018 (as labelled on the page; described as predicted)

    People diagnosed with myeloma in the UK; the page states that it is predicted that almost 4 in 10 (37.8%) survive their disease for ten years or more (2018). For diagnosis at ages 15-44 the page gives 82.5% for females and 73.8% for males, and for ages 75-99 it gives 20.6% for females and 20.2% for males (2018).

    Described on the page as predicted, so a modelled estimate rather than an observed ten-year follow-up (the method was not read). The page says ten-year survival has increased in all broad age groups in both women and men since the early 1970s. Same series and measure caveats as the 1970s value.

    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.

Newly diagnosed, transplant not planned

Adults with newly diagnosed multiple myeloma who were ineligible for, or not planning, immediate autologous stem-cell transplantation (VISTA, FIRST, SWOG S0777, ALCYONE, MAIA, IMROZ) · Any setting · endpoint: PFS

Results are not comparable across trials.

Eras, controls and populations differ: melphalan-prednisone (VISTA), melphalan-prednisone-thalidomide (FIRST), lenalidomide-dexamethasone (SWOG S0777, MAIA) and bortezomib-melphalan-prednisone or bortezomib-lenalidomide-dexamethasone (ALCYONE, IMROZ). SWOG S0777 stratified by intent to transplant and allowed ECOG performance status 0 to 3; IMROZ enrolled people aged 18 to 80. VISTA reports time to progression, not progression-free survival, and is drawn with a distinct marker. Medians are plotted where both arms report one: FIRST's continuous lenalidomide-dexamethasone arm (its 18-cycle arm is not drawn) and MAIA's long-term update, not its primary analysis. ALCYONE (18 months) and IMROZ (60 months) report progression-free percentages at landmarks, which are listed but not plotted on the median axis. CEPHEUS (mixed transplant-ineligible and transplant-deferred population) is not drawn because the record holds a hazard ratio only. The 1962 to 1969 melphalan record is a needs-review milestone with no plottable result. Compare only each trial's own two arms; the chart is not a pooled or network 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.

0204060PFS, median (months)2008201420142017VISTAFIRSTSWOG S0777MAIA
  • experimental arm
  • control arm
  • different endpoint from the lane's
  • step line through experimental values
PFS, median, across 4 trials in this lane. VISTA (2008): experimental 24 months vs control 16.6 months; FIRST (2014): experimental 25.5 months vs control 21.2 months; SWOG S0777 (2014): experimental 43 months vs control 30 months; MAIA (2017): experimental 61.9 months vs control 34.4 months.
Data table
TrialYearEndpointControl (months)Experimental (months)
VISTA2008TTP (differs from lane)16.6 months24 months
FIRST2014PFS21.2 months25.5 months
SWOG S07772014PFS30 months43 months
MAIA2017PFS34.4 months61.9 months
ALCYONE2017PFS (not plotted: different measure or time point)50.2 %71.6 %
IMROZ2019PFS (not plotted: different measure or time point)45.2 %63.2 %

Newly diagnosed, transplant-eligible

Adults with newly diagnosed multiple myeloma eligible for high-dose melphalan with autologous stem-cell transplantation (IFM 2009, DETERMINATION, GRIFFIN, PERSEUS; the 1990s transplant trials appear as milestones only) · Any setting · endpoint: PFS

Results are not comparable across trials.

IFM 2009 and DETERMINATION compare RVD with and without transplantation, so their experimental arm is the transplant arm and both control arms could receive transplant later (salvage transplantation is described in the milestone); maintenance differed (lenalidomide for one year in IFM 2009, until progression in DETERMINATION). GRIFFIN (phase 2) and PERSEUS add daratumumab to RVD or VRd and report progression-free percentages at landmarks (24 and 48 months), which are listed but not plotted on the median axis. Primary endpoints differ (stringent complete response in GRIFFIN, progression-free survival in PERSEUS). CASSIOPEIA is not drawn because median progression-free survival was not reached in either group. GMMG-HD7 part 1 reports induction only. IFM 90, MRC Myeloma VII and IFM 94 predate bortezomib and lenalidomide, report event-free and overall survival without stating a primary endpoint in the abstracts, and are not plotted against progression-free-survival trials. Compare only each trial's own two arms.

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.

020406080PFS, median (months)20172017IFM 2009DETERMINATION
  • experimental arm
  • control arm
  • different endpoint from the lane's
  • step line through experimental values
PFS, median, across 2 trials in this lane. IFM 2009 (2017): experimental 50 months vs control 36 months; DETERMINATION (2017): experimental 67.5 months vs control 46.2 months.
Data table
TrialYearEndpointControl (months)Experimental (months)
IFM 20092017PFS36 months50 months
DETERMINATION2017PFS46.2 months67.5 months
GRIFFIN2019PFS (not plotted: different measure or time point)89.8 %95.8 %
PERSEUS2019PFS (not plotted: different measure or time point)67.7 %84.3 %

Lenalidomide maintenance

Adults with newly diagnosed multiple myeloma receiving lenalidomide as maintenance: after autologous transplant in IFM 2005-02 and CALGB 100104; ENDURANCE (no up-front transplant) is listed as a milestone but not plotted · Maintenance · endpoint: PFS

Results are not comparable across trials.

IFM 2005-02 (patients younger than 65 with non-progressive disease after transplant) and CALGB 100104 (patients younger than 71 with stable disease or a response 100 days after transplant) compared lenalidomide with placebo; CALGB 100104 reports time to progression, not progression-free survival, and is drawn with a distinct marker. CALGB 100104 was unblinded in 2009 and many placebo patients crossed over, which affects its survival comparison. The pooled three-trial meta-analysis is not drawn so that its trials are not counted twice. ENDURANCE enrolled standard-risk patients who did not have up-front transplant, used a proteasome inhibitor-lenalidomide induction and compared fixed-duration with continuous lenalidomide; its milestone says it should not be plotted with the post-transplant trials. Compare only each trial's own two arms.

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.

01020304050PFS, median (months)20122012IFM 2005-02CALGB 100104
  • experimental arm
  • control arm
  • different endpoint from the lane's
  • step line through experimental values
PFS, median, across 2 trials in this lane. IFM 2005-02 (2012): experimental 41 months vs control 23 months; CALGB 100104 (2012): experimental 46 months vs control 27 months.
Data table
TrialYearEndpointControl (months)Experimental (months)
IFM 2005-022012PFS23 months41 months
CALGB 1001042012TTP (differs from lane)27 months46 months

Relapsed or refractory, earlier relapse

Adults with relapsed or refractory multiple myeloma after one or more previous lines of therapy (APEX, ENDEAVOR and BELLINI: one to three; MM-009, MM-010, DREAMM-7, MonumenTAL-3: at least one) · Relapsed / refractory · endpoint: PFS

Results are not comparable across trials.

Eras run from 2003 to 2026 and controls differ: dexamethasone (APEX), placebo plus dexamethasone (MM-009, MM-010), lenalidomide-dexamethasone (ASPIRE, POLLUX), bortezomib-dexamethasone (ENDEAVOR, BELLINI), daratumumab-bortezomib-dexamethasone (DREAMM-7), PVd (DREAMM-8) and investigator-selected regimens (MajesTEC-3, MajesTEC-9, MonumenTAL-3). MajesTEC-9 required prior anti-CD38 antibody and lenalidomide; DREAMM-8 enrolled lenalidomide-exposed patients. APEX, MM-009 and MM-010 report time to progression, not progression-free survival, and are drawn with a distinct marker; MM-009 and MM-010 each stand alone. BELLINI's median is plotted, but its milestone records an overall survival result that points the other way. Medians are plotted only where both arms report one. Trials whose experimental-arm median was not reached (IKEMA, CARTITUDE-4, CASTOR) are not drawn, because a median that was not reached cannot be plotted. POLLUX, DREAMM-8, MajesTEC-3, MajesTEC-9 and MonumenTAL-3 report progression-free percentages at landmarks (12, 12, 36, 18 and 24 months), which are listed but not plotted on the median axis; MonumenTAL-3's talquetamab-daratumumab arm is not drawn. Several are interim analyses. Compare only each trial's own two arms.

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.

010203040PFS, median (months)2003200620062012201220202023APEXMM-009MM-010ASPIREENDEAVORBELLINIDREAMM-7
  • experimental arm
  • control arm
  • different endpoint from the lane's
  • step line through experimental values
PFS, median, across 7 trials in this lane. APEX (2003): experimental 6.22 months vs control 3.49 months; MM-009 (2006): experimental 11.1 months vs control 4.7 months; MM-010 (2006): experimental 11.3 months vs control 4.7 months; ASPIRE (2012): experimental 26.3 months vs control 17.6 months; ENDEAVOR (2012): experimental 18.7 months vs control 9.4 months; BELLINI (2020): experimental 22.4 months vs control 11.5 months; DREAMM-7 (2023): experimental 36.6 months vs control 13.4 months.
Data table
TrialYearEndpointControl (months)Experimental (months)
APEX2003TTP (differs from lane)3.49 months6.22 months
MM-0092006TTP (differs from lane)4.7 months11.1 months
MM-0102006TTP (differs from lane)4.7 months11.3 months
ASPIRE2012PFS17.6 months26.3 months
ENDEAVOR2012PFS9.4 months18.7 months
BELLINI2020PFS11.5 months22.4 months
DREAMM-72023PFS13.4 months36.6 months
POLLUX2015PFS (not plotted: different measure or time point)60.1 %83.2 %
DREAMM-82023PFS (not plotted: different measure or time point)51 %71 %
MajesTEC-32025PFS (not plotted: different measure or time point)29.7 %83.4 %
MajesTEC-92025PFS (not plotted: different measure or time point)26.9 %69.8 %
MonumenTAL-32025PFS (not plotted: different measure or time point)51.2 %81.3 %

Relapsed or refractory, later relapse

Adults with relapsed or refractory multiple myeloma after at least two previous lines (ICARIA-MM, CANOVA and DREAMM-3: at least two; KarMMa-3: two to four previous regimens) · Relapsed / refractory · endpoint: PFS

Results are not comparable across trials.

Entry rules differ: ICARIA-MM required prior lenalidomide and a proteasome inhibitor and excluded patients refractory to an anti-CD38 antibody; CANOVA enrolled only t(11;14)-positive patients; DREAMM-3 required two or more consecutive cycles of both lenalidomide and a proteasome inhibitor; KarMMa-3 required refractoriness to the last regimen. Controls differ (pomalidomide-dexamethasone in ICARIA-MM, CANOVA and DREAMM-3; standard regimens in KarMMa-3). DREAMM-3 tested single-agent belantamab mafodotin and did not show longer progression-free survival than pomalidomide-dexamethasone; its primary-analysis medians are plotted and its final analysis was descriptive. CANOVA did not reach its progression-free survival goal. Single-arm studies (KarMMa, CARTITUDE-1, DREAMM-2, MajesTEC-1, MonumenTAL-1, MagnetisMM-3, LINKER-MM1) are not drawn. Compare only each trial's own two arms.

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.

05101520PFS, median (months)2019202020212023ICARIA-MMCANOVAKarMMa-3DREAMM-3
  • experimental arm
  • control arm
  • different endpoint from the lane's
  • step line through experimental values
PFS, median, across 4 trials in this lane. ICARIA-MM (2019): experimental 11.5 months vs control 6.5 months; CANOVA (2020): experimental 9.9 months vs control 5.8 months; KarMMa-3 (2021): experimental 13.3 months vs control 4.4 months; DREAMM-3 (2023): experimental 11.2 months vs control 7 months.
Data table
TrialYearEndpointControl (months)Experimental (months)
ICARIA-MM2019PFS6.5 months11.5 months
CANOVA2020PFS5.8 months9.9 months
KarMMa-32021PFS4.4 months13.3 months
DREAMM-32023PFS7 months11.2 months

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.

Newly diagnosed myeloma, transplant not planned: first-line regimens

Adults with newly diagnosed multiple myeloma who were ineligible for, or not planning, immediate autologous stem-cell transplantation · Any setting

  1. Chemotherapy1Melphalan + prednisoneMelphalan, then melphalan plus prednisone, in myeloma (1962)
  2. Targeted2Bortezomib + melphalan + prednisoneVISTA: bortezomib added to melphalan-prednisone, first line (2008)
  3. Targeted3Lenalidomide + dexamethasoneFIRST and SWOG S0777: lenalidomide-based first-line treatment (2014)
  4. Targeted4Bortezomib + lenalidomide + dex (VRd)FIRST and SWOG S0777: lenalidomide-based first-line treatment (2014)
  5. Immunotherapy5Daratumumab + VMPDaratumumab first line without transplant: ALCYONE, MAIA, CEPHEUS (2017)
  6. Immunotherapy6Daratumumab + lenalidomide + dexDaratumumab first line without transplant: ALCYONE, MAIA, CEPHEUS (2017)
  7. Immunotherapy7Isatuximab + VRdIsatuximab: ICARIA-MM, IKEMA, HD7 and IMROZ (2019)
2025. Based only on the trials cited in each step; guidelines and local practice vary. Daratumumab with VMP (FDA May 2018) and with Rd (June 2019), and isatuximab with VRd (September 2024), were tested against the regimen alone.
Text version
  • 1970: Melphalan + prednisone
  • 2010: Melphalan + prednisone → Bortezomib + melphalan + prednisone
  • 2016: Melphalan + prednisone → Bortezomib + melphalan + prednisone → Lenalidomide + dexamethasone → Bortezomib + lenalidomide + dex (VRd)
  • 2025: Melphalan + prednisone → Bortezomib + melphalan + prednisone → Lenalidomide + dexamethasone → Bortezomib + lenalidomide + dex (VRd) → Daratumumab + VMP → Daratumumab + lenalidomide + dex → Isatuximab + VRd

Relapsed or refractory myeloma: regimens tested over time

Adults with relapsed or refractory multiple myeloma · Relapsed / refractory

  1. Targeted1BortezomibBortezomib in relapsed myeloma: SUMMIT phase 2 to APEX (2003)
  2. Targeted2Lenalidomide + dexamethasoneLenalidomide plus dexamethasone in relapsed myeloma: MM-009, MM-010 (2006)
  3. Targeted3Carfilzomib-based regimensCarfilzomib: accelerated approval to ASPIRE and ENDEAVOR (2012)
  4. Immunotherapy4Daratumumab-based regimensDaratumumab: anti-CD38 antibody from single agent to CASTOR/POLLUX (2015)
  5. Immunotherapy5Isatuximab-based regimensIsatuximab: ICARIA-MM, IKEMA, HD7 and IMROZ (2019)
  6. Cell therapy & transplant6BCMA CAR T-cell therapyBCMA CAR T cells: ide-cel and cilta-cel, from KarMMa to CARTITUDE-4 (2021)
  7. Antibody–drug conjugate7Belantamab mafodotin combinationsBelantamab mafodotin: withdrawn in 2023, approved again in 2025 (2023)
  8. Immunotherapy8Teclistamab / talquetamab combinationsBispecifics move earlier: MajesTEC-3, MajesTEC-9, MonumenTAL-3 (2025)
2026. Based only on the trials cited in each step; guidelines and local practice vary. Belantamab mafodotin with bortezomib-dexamethasone (FDA October 2025) and teclistamab with daratumumab (FDA March 2026) were approved for earlier lines.
Text version
  • 2005: Bortezomib
  • 2016: Bortezomib → Lenalidomide + dexamethasone → Carfilzomib-based regimens → Daratumumab-based regimens
  • 2021: Bortezomib → Lenalidomide + dexamethasone → Carfilzomib-based regimens → Daratumumab-based regimens → Isatuximab-based regimens → BCMA CAR T-cell therapy
  • 2026: Bortezomib → Lenalidomide + dexamethasone → Carfilzomib-based regimens → Daratumumab-based regimens → Isatuximab-based regimens → BCMA CAR T-cell therapy → Belantamab mafodotin combinations → Teclistamab / talquetamab combinations

Reversals and dead ends

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

  • 2020

    Venetoclax in myeloma: BELLINI signals harm, CANOVA misses PFS

    Venetoclax blocks BCL-2, a protein that helps some myeloma cells survive. In an unselected group with relapsed myeloma, adding it to bortezomib and dexamethasone delayed progression but was followed by more deaths, mostly from infection. A later trial in people whose myeloma has a t(11;14) change did not reach its progression-free survival goal.

    BELLINI (venetoclax or placebo plus Vd, n=291): median PFS 22.4 versus 11.5 months, HR 0.63 (95% CI 0.44 to 0.90); eight fatal infections with venetoclax, none with placebo. Final analysis at 45.6 months: OS HR 1.19 (0.80 to 1.77; P=0.39). CANOVA (venetoclax-dexamethasone versus Pd, t(11;14)-positive, n=263): median PFS 9.9 versus 5.8 months, HR 0.823 (0.596 to 1.136; P=0.24), primary end point not met; OS HR 0.856 (0.612 to 1.197).

  • 2023

    Belantamab mafodotin: withdrawn in 2023, approved again in 2025

    Belantamab mafodotin, an antibody-drug conjugate aimed at BCMA, was approved in the US in 2020 on response rates. Its required follow-up trial did not show longer time without progression than pomalidomide and dexamethasone, and the US licence was withdrawn in 2023. Two later trials of combinations reported longer progression-free survival, and the US approved a combination in 2025.

    DREAMM-2 (randomised phase 2, n=196): ORR 31% (2.5 mg/kg) and 34% (3.4 mg/kg). DREAMM-3 (versus Pd, n=325), primary analysis: median PFS 11.2 versus 7.0 months, HR 1.03 (95% CI 0.72 to 1.47), P=0.56; final analysis PFS HR 0.87 (0.64 to 1.18), OS HR 0.98 (0.73 to 1.30). DREAMM-7 (BVd versus DVd): PFS HR 0.41 (0.31 to 0.53). DREAMM-8 (BPd versus PVd): HR 0.52 (0.37 to 0.73). Ocular events 79% and 89%.

Today and tomorrow

Standard of care today

Any setting

Diagnosis, definition, staging and response assessment. Guideline documents are cited by identifier only; their recommendations were not read for this page, and whether each is the current edition was not checked:

  • NCCN Clinical Practice Guidelines in Oncology, Multiple Myeloma, Version 5.2026 (J Natl Compr Canc Netw 2026, PMID 41671464)
  • the EHA-EMN Evidence-Based Guidelines for diagnosis, treatment and follow-up (Nat Rev Clin Oncol 2025, PMID 40624367)
  • and the EHA-ESMO Clinical Practice Guidelines (Ann Oncol 2021, PMID 33549387
  • Hemasphere 2021, PMID 33554050
  • corrigenda PMIDs 34857439 and 35810138). The documents that define myeloma, stage it and grade response are described in the timeline: the International Myeloma Working Group diagnostic criteria (2014), the International Staging System (2005) and its revisions R-ISS (2015) and R2-ISS (2022), and the IMWG consensus criteria for response and minimal residual disease (2016). At FDA, the Oncologic Drugs Advisory Committee voted 12 to 0 on 12 April 2024 (advisory) that the evidence supports MRD as an accelerated approval endpoint in myeloma trials, and a draft guidance of January 2026 (non-binding, marked not for implementation) discusses MRD negativity and complete response as endpoints to support accelerated approval
Guideline: Kumar SK, Callander NS, Adekola K, Anderson LD Jr, Baljevic M, Baz R, et al 2026Guideline: Dimopoulos MA, Terpos E, Boccadoro M, Moreau P, Mateos MV, Zweegman S, et al 2025Guideline: Dimopoulos MA, Moreau P, Terpos E, Mateos MV, Zweegman S, Cook G, et al 2021Guideline: Dimopoulos MA, Moreau P, Terpos E, Mateos MV, Zweegman S, Cook G, et al 2021Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, et al 2014Greipp PR, San Miguel J, Durie BG, Crowley JJ, Barlogie B, Bladé J, et al 2005Palumbo A, Avet-Loiseau H, Oliva S, Lokhorst HM, Goldschmidt H, Rosinol L, et al 2015D'Agostino M, Cairns DA, Lahuerta JJ, Wester R, Bertsch U, Waage A, et al 2022Kumar S, Paiva B, Anderson KC, Durie B, Landgren O, Moreau P, et al 2016US Food and Drug Administration 2024US Food and Drug Administration 2026
Any setting
Newly diagnosed myeloma, people eligible for autologous stem cell transplantation. FDA letters read: daratumumab with bortezomib, thalidomide and dexamethasone (26 September 2019) and daratumumab hyaluronidase with bortezomib, lenalidomide and dexamethasone for induction and consolidation (30 July 2024). Thalidomide received accelerated approval for newly diagnosed myeloma on 25 May 2006 (the letter cites the accelerated approval regulations, 21 CFR 314.510 and 314.520, without a transplant criterion). Two randomised trials, IFM/DFCI 2009 and DETERMINATION, compared lenalidomide-bortezomib-dexamethasone with and without early transplantation (see the timeline). No EMA document on these indications was read, and guideline text was not read.
U 2019U 2024US Food and Drug Administration 2006Attal M, Lauwers-Cances V, Hulin C, Leleu X, Caillot D, Escoffre M, et al 2017Richardson PG, Jacobus SJ, Weller EA, Hassoun H, Lonial S, Raje NS, et al 2022
Any setting

Newly diagnosed myeloma, people not eligible for transplantation. FDA letters read:

  • daratumumab with bortezomib, melphalan and prednisone (7 May 2018)
  • daratumumab with lenalidomide and dexamethasone (27 June 2019)
  • isatuximab with bortezomib, lenalidomide and dexamethasone (20 September 2024)
  • and daratumumab hyaluronidase with bortezomib, lenalidomide and dexamethasone (27 January 2026). A supplement letter of 17 February 2015 approved lenalidomide with dexamethasone for patients with myeloma (the letter quotes the proposed indication). No EMA document on these indications was read, and guideline sequencing was not read
U 2018U 2019U 2024U 2026US Food and Drug Administration 2015
Maintenance
Maintenance. Lenalidomide has an FDA indication as maintenance following autologous stem cell transplantation (supplement letter of 22 February 2017). ENDURANCE (N Engl J Med 2026; abstract read) compared continuous with 2-year lenalidomide after induction in people with standard-risk newly diagnosed myeloma who were not undergoing up-front transplantation and reports no significant difference in overall survival (see the timeline). The EU maintenance indication wording and guideline text were not read.
US Food and Drug Administration 2017Kumar S, Jacobus S, Cohen A, Weiss M, Callander N, Singh A, et al 2026
Any setting
High-risk smouldering myeloma. An FDA letter of 6 November 2025 approved daratumumab hyaluronidase as monotherapy for adults with high-risk smoldering myeloma; the letter does not use the word accelerated, and the randomised trial in the timeline is AQUILA (daratumumab versus active monitoring). The EMA EPAR page for Darzalex lists use on its own in adults with smouldering myeloma at high risk of progression and states that, at the time of approval, Darzalex was the first medicine authorised for smouldering myeloma; the date of that EU extension was not read. Guideline text was not read.
US Food and Drug Administration 2025European Medicines Agency 2026Dimopoulos MA, Voorhees PM, Schjesvold F, Cohen YC, Hungria V, Sandhu I, et al 2025
Relapsed / refractory

Relapsed or refractory myeloma, proteasome inhibitors, immunomodulatory drugs and anti-CD38 antibodies; FDA letters read. Bortezomib:

  • accelerated approval on 13 May 2003 after at least two prior therapies, and a supplement letter of 25 March 2005 for at least one prior therapy that states approval of the supplement fulfils the accelerated-approval commitments. Lenalidomide with dexamethasone after at least one prior therapy: 29 June 2006 (the letter cites 21 CFR 314.520, Subpart H, not 314.510, and does not use the word accelerated). Carfilzomib: accelerated approval on 20 July 2012
  • with lenalidomide and dexamethasone after at least one prior therapy on 24 July 2015
  • a supplement letter of 21 January 2016 based on ENDEAVOR with a Subpart H fulfilled section. Daratumumab: accelerated approval on 16 November 2015 after at least three prior lines
  • supplement letters of 21 November 2016 (headed fulfilment of a postmarketing requirement, each with a Subpart E fulfilled section stating that approval of the supplement fulfils the commitments under 21 CFR 601.41
  • the letters do not use the word converted) for use with lenalidomide-dexamethasone and with bortezomib-dexamethasone after at least one prior therapy. Isatuximab: with pomalidomide and dexamethasone on 2 March 2020 (at least two prior therapies including lenalidomide and a proteasome inhibitor)
  • with carfilzomib and dexamethasone on 31 March 2021 (1 to 3 prior lines). EMA EPAR pages: Velcade authorised 26 April 2004, Kyprolis 19 November 2015 and Sarclisa 30 May 2020
  • Darzalex received a conditional authorisation on 20 May 2016 that was switched to a standard authorisation on 28 April 2017. Indication wording at authorisation was not read, and guideline sequencing was not read
US Food and Drug Administration 2003US Food and Drug Administration 2005US Food and Drug Administration 2006U 2012U 2015U 2016U 2015U 2016U 2016U 2020U 2021European Medicines Agency 2026European Medicines Agency 2026European Medicines Agency 2026European Medicines Agency 2026
Relapsed / refractory

Relapsed or refractory myeloma, newer agents in earlier lines; FDA letters read. Belantamab mafodotin with bortezomib and dexamethasone after at least two prior lines including a proteasome inhibitor and an immunomodulatory agent:

  • 23 October 2025 (see the hooks for the 2020 approval and 2023 revocation). Idecabtagene vicleucel after two or more prior lines including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody: 4 April 2024. Ciltacabtagene autoleucel: a supplement letter of 5 April 2024 extends the indication on the basis of CARTITUDE-4 (the letter does not restate the wording). Teclistamab with daratumumab hyaluronidase after at least one prior line including a proteasome inhibitor and an immunomodulatory agent: 5 March 2026. Iberdomide (Zenbexus) with daratumumab hyaluronidase and dexamethasone after at least one prior line including a proteasome inhibitor and an immunomodulatory agent: accelerated approval on 13 August 2026 (NDA 221075 letter)
  • the FDA list of ongoing cancer accelerated approvals (content current 19 October 2026) names the required confirmatory randomised trial of iberdomide with daratumumab hyaluronidase and dexamethasone against daratumumab hyaluronidase, bortezomib and dexamethasone, with progression-free survival as the primary endpoint. EMA: Blenrep was authorised again on 23 July 2025 (EPAR page)
  • EU indication details for the other products in this entry were not read. Guideline text was not read
U 2025U 2024U 2024U 2026U 2026FDA 2026European Medicines Agency 2026
Relapsed / refractory

Relapsed or refractory myeloma after four or more prior lines of therapy; FDA letters read. CAR T-cell products:

  • idecabtagene vicleucel (26 March 2021) and ciltacabtagene autoleucel (28 February 2022), each approved after four or more prior lines including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody (neither letter uses accelerated-approval wording). Bispecific antibodies: teclistamab (accelerated approval on 25 October 2022
  • a letter of 5 March 2026 converts it to traditional approval for monotherapy after at least four prior lines), talquetamab (accelerated, 9 August 2023), elranatamab (accelerated, 14 August 2023) and linvoseltamab (accelerated, 2 July 2025). The FDA list of ongoing cancer accelerated approvals (content current 19 October 2026) shows Talvey, Elrexfio and Lynozyfic with confirmatory randomised-trial requirements
  • no conversion letter for them was found. The FDA list of withdrawn accelerated approvals (content current 5 October 2026) shows Blenrep (approved 5 August 2020, withdrawn 6 February 2023) and Pepaxto (melphalan flufenamide
  • approved 26 February 2021, withdrawn 23 February 2024
  • the list gives no reason). The same list also shows Farydak (panobinostat with bortezomib and dexamethasone after at least 2 prior regimens
  • approved 23 February 2015, withdrawn 24 March 2022), outside the four-prior-lines population of this entry. EMA EPAR pages: conditional authorisations for Abecma (18 August 2021, standard from 19 March 2024), Carvykti (25 May 2022, standard from 19 April 2024), Tecvayli (23 August 2022, standard from 20 August 2026), Talvey (21 August 2023), Elrexfio (7 December 2023) and Lynozyfic (23 April 2025)
  • the Talvey and Elrexfio EPAR pages state at least three prior therapies, which differs from the US wording. Guideline text was not read
U 2021U 2022U 2022U 2026U 2023U 2023U 2025FDA 2026FDA 2026European Medicines Agency 2026European Medicines Agency 2026European Medicines Agency 2026European Medicines Agency 2026European Medicines Agency 2026European Medicines Agency 2026

Trials to watch

  • CARTITUDE-5 NCT04923893

    In newly diagnosed myeloma for which transplantation is not planned as initial therapy, does bortezomib-lenalidomide-dexamethasone (VRd) followed by ciltacabtagene autoleucel differ from VRd followed by lenalidomide-dexamethasone in progression-free survival (the registry's primary outcome)? Registry record: randomised phase 3, 743 (actual), sponsor Janssen Research & Development; registry status active, not recruiting (status verified 2026-09); primary completion 2029-02-14 (estimated); no results posted. No peer-reviewed report was found in PubMed on 21 October 2026.

  • CARTITUDE-6 NCT05257083

    In newly diagnosed myeloma in people eligible for transplantation, does daratumumab-bortezomib-lenalidomide-dexamethasone (DVRd) followed by ciltacabtagene autoleucel differ from DVRd followed by autologous stem cell transplantation in progression-free survival and in sustained MRD-negative complete response (the registry's two primary outcomes)? Registry record: randomised phase 3, 759 (actual), sponsor Stichting European Myeloma Network; registry status active, not recruiting (status verified 2025-12); primary completion 2033-06 (estimated); no results posted. No peer-reviewed report was found in PubMed on 21 October 2026.

  • MajesTEC-4 NCT05243797

    As maintenance after autologous stem cell transplantation in newly diagnosed myeloma, does teclistamab with lenalidomide, or teclistamab alone, differ from lenalidomide alone in progression-free survival and in MRD-negative complete response (the registry's two primary outcomes)? Registry record: randomised phase 3 with three arms, 1594 estimated, sponsor European Myeloma Network B.V.; registry status recruiting (status verified 2026-10); primary completion 2028-04 (estimated); no results posted. No peer-reviewed report was found in PubMed on 21 October 2026.

  • MajesTEC-7 NCT05552222

    In newly diagnosed myeloma in people who are ineligible for, or not intended for, autologous stem cell transplantation as initial therapy, do teclistamab-daratumumab-lenalidomide or talquetamab-daratumumab-lenalidomide differ from daratumumab-lenalidomide-dexamethasone in progression-free survival and in 12-month MRD-negative complete response (the registry's two primary outcomes)? Registry record: randomised phase 3 with three arms, 1590 estimated, sponsor Janssen Research & Development; registry status recruiting (status verified 2026-09); primary completion 2031-04-30 (estimated); no results posted. No peer-reviewed report was found in PubMed on 21 October 2026.

  • MagnetisMM-5 NCT05020236

    In relapsed or refractory myeloma after at least one prior line including lenalidomide and a proteasome inhibitor (registry official title), does elranatamab alone, or with daratumumab, differ from daratumumab-pomalidomide-dexamethasone in progression-free survival per IMWG criteria in the randomised part 2 (the registry's part 2 primary outcome; parts 1 and 3 have safety primary outcomes)? Registry record: open-label randomised phase 3, 893 estimated, sponsor Pfizer; registry status recruiting (status verified 2026-08); the registry lists primary completion as 2026-02-26 (actual); no results posted. No peer-reviewed report was found in PubMed on 21 October 2026.

  • iMMagine-3 NCT06413498

    In relapsed or refractory myeloma, does anitocabtagene autoleucel differ from standard of care therapy in progression-free survival and in the MRD-negative complete response rate at 9 months (the registry's two primary outcomes)? Registry record: randomised, open-label phase 3, 452 (actual), sponsor Kite, a Gilead Company; registry status active, not recruiting (status verified 2026-07); primary completion 2028-07 (estimated); no results posted. No peer-reviewed phase 3 report was found in PubMed on 21 October 2026.

Pioneers

References

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2012TreatmentTargeted

majorMaintenance

Lenalidomide maintenance after autologous transplant

After a stem cell transplant, people with myeloma were randomly given lenalidomide or placebo until the disease progressed. In two trials, progression took longer with lenalidomide, but second cancers were more frequent. One trial reported fewer deaths with lenalidomide; the other found similar survival at four years. A pooled analysis of three trials reported longer survival.

IFM 2005-02 (n=614, age under 65): median PFS (primary) 41 versus 23 months, HR 0.50 (P<0.001); second primary cancers 3.1 versus 1.2 per 100 patient-years. CALGB 100104 (n=460, under 71): median time to progression 46 versus 27 months (P<0.001); deaths 15% versus 23% (P=0.03). Patient-level meta-analysis of three trials (n=1,208): median PFS 52.8 versus 23.5 months (HR 0.48); OS HR 0.75 (95% CI 0.63 to 0.90). FDA maintenance indication 22 February 2017.

Standard before

Placebo was the comparator in IFM 2005-02 and CALGB 100104; the meta-analysis compared lenalidomide with placebo or observation.

What changed

On 22 February 2017 the FDA expanded the Revlimid indication to include multiple myeloma maintenance following autologous hematopoietic stem cell transplantation.

Why it mattered

Two randomised, placebo-controlled trials reported a longer time to progression with lenalidomide after transplant, and a meta-analysis of patient-level data reported an overall survival benefit, set against more second primary cancers. It defined the post-transplant maintenance setting; how long to continue was later tested in ENDURANCE, in a different population.

Caveats

  • The meta-analysis compares lenalidomide with placebo or observation across three trials, one of which (GIMEMA RV-MM-PI-209) is not described separately here.
  • CALGB 100104 was unblinded in 2009 after a planned interim analysis, and 86 of 128 eligible placebo patients crossed over to lenalidomide, which affects the survival comparison.
  • Second primary cancers were more frequent with lenalidomide in both trials (IFM 2005-02: 3.1 versus 1.2 per 100 patient-years; CALGB 100104: 18 patients versus 6).
  • IFM 2005-02 reported similar overall survival at 4 years; a survival difference was reported in CALGB 100104 (deaths 15% versus 23%) and in the meta-analysis (median follow-up 79.5 months).
  • The FDA letter approving the maintenance indication does not name the trials. The duration question is examined in ENDURANCE, which enrolled a different population (no up-front transplant).