GLOW
A Study of the Combination of Ibrutinib Plus Venetoclax Versus Chlorambucil Plus Obinutuzumab for the First-line Treatment of Participants With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
Phase 3N = 211NCT03462719
- Population
- Previously untreated CLL, aged 65 or older, or 18 to 64 with a Cumulative Illness Rating Scale score above 6 or creatinine clearance below 70 ml/min.
- Design
- Open-label randomised phase 3 at 67 hospital centres in 14 countries: ibrutinib-venetoclax (3 cycles of ibrutinib lead-in, then 12 cycles of ibrutinib plus venetoclax) versus 6 cycles of chlorambucil-obinutuzumab. Registry actual enrolment equals the 211 randomised.
- Primary endpoint
- PFS
- Arms
- Ibrutinib-venetoclax (experimental, n = 106): 3 cycles ibrutinib lead-in, then 12 cycles ibrutinib plus venetoclax
- Chlorambucil-obinutuzumab (control, n = 105): 6 cycles of chlorambucil plus obinutuzumab
- People
- Kater AP
PFSHR 0.216 (95% CI 0.131–0.357)Δ Undetectable MRD rate+34.7 pointsPFSHR 0.214 (95% CI 0.138–0.334)Δ 42-month PFS+49.8 points
Show the numbers
| Endpoint | Analysis | Ibrutinib-venetoclax | Chlorambucil-obinutuzumab | Effect |
|---|---|---|---|---|
| PFSAll randomised patients (106 vs 105) | primarymedian follow-up 27.7 monthsKater 2022 | — | — | HR 0.216 (95% CI 0.131–0.357)P<0.001Progression-free survival assessed by an independent review committee; 22 events with ibrutinib-venetoclax and 67 with chlorambucil-obinutuzumab. |
| Undetectable MRD rateAll randomised patients (106 vs 105)Best undetectable MRD rate in bone marrow measured by next-generation sequencing | primaryKater 2022 | 55.7% | 21% | P<0.001Best undetectable MRD rate in bone marrow by next-generation sequencing, a secondary endpoint. Sustained undetectable MRD in peripheral blood from 3 to 12 months after end of treatment: 84.5% with ibrutinib-venetoclax versus 29.3%. |
| PFSIntention-to-treat population (211 randomised) | long term-updatemedian follow-up 46 monthsNiemann 2023 | 74.6% at 42 mo (65–82%) | 24.8% at 42 mo (16.5–34.1%) | HR 0.214 (95% CI 0.138–0.334)P<0.0001Four-year follow-up. 15 deaths in the ibrutinib-venetoclax group and 30 in the chlorambucil-obinutuzumab group. |
| Endpoint | Analysis | Ibrutinib-venetoclax | Chlorambucil-obinutuzumab | Effect |
|---|---|---|---|---|
| PFSAll randomised patients (106 vs 105) | primarymedian follow-up 27.7 monthsKater 2022 | — | — | HR 0.216 (95% CI 0.131–0.357)P<0.001Progression-free survival assessed by an independent review committee; 22 events with ibrutinib-venetoclax and 67 with chlorambucil-obinutuzumab. |
| Undetectable MRD rateAll randomised patients (106 vs 105)Best undetectable MRD rate in bone marrow measured by next-generation sequencing | primaryKater 2022 | 55.7% | 21% | P<0.001Best undetectable MRD rate in bone marrow by next-generation sequencing, a secondary endpoint. Sustained undetectable MRD in peripheral blood from 3 to 12 months after end of treatment: 84.5% with ibrutinib-venetoclax versus 29.3%. |
| PFSIntention-to-treat population (211 randomised) | long term-updatemedian follow-up 46 monthsNiemann 2023 | 74.6% at 42 mo (65–82%) | 24.8% at 42 mo (16.5–34.1%) | HR 0.214 (95% CI 0.138–0.334)P<0.0001Four-year follow-up. 15 deaths in the ibrutinib-venetoclax group and 30 in the chlorambucil-obinutuzumab group. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| PFS | 0.216 | 0.131–0.357 |
| PFS | 0.214 | 0.138–0.334 |
Appears in
Sources
Kater AP, Owen C, Moreno C, Follows G, Munir T, Levin MD, et al. Fixed-Duration Ibrutinib-Venetoclax in Patients with Chronic Lymphocytic Leukemia and Comorbidities. NEJM Evid. 2022;1(7):EVIDoa2200006.
Niemann CU, Munir T, Moreno C, Owen C, Follows GA, Benjamini O, et al. Fixed-duration ibrutinib-venetoclax versus chlorambucil-obinutuzumab in previously untreated chronic lymphocytic leukaemia (GLOW): 4-year follow-up from a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2023;24(12):1423-1433.