Frontline trials of BTK-BCL2 inhibitor combinations in CLL
| Reference . | Regimen . | Eligibility (n) . | Response rate . | PFS . | MRD . |
|---|---|---|---|---|---|
| Jain et al9 | Ibrutinib + venetoclax | del(17p), TP53 mutation, del(11q), unmutated IGHV, or ≥65 years old (n = 120; n = 27 del(17p)/TP53 mutation) | ORR 100% (CR 88%) | 4-year PFS: 95% 4-year PFS for del(17p)/TP53 mutation: 91% | BM-uMRD at 12 cycles: 56% BM-uMRD at 24 cycles: 66% |
| CAPTIVATE10-12 | Ibrutinib + venetoclax | ≤70 years old MRD cohort (n = 164) FD cohort (n = 159) | MRD cohort: ORR 97% (CR 46%) FD cohort: ORR 96% (CR 55%) | MRD cohort: Estimated 30-month PFS for all randomized cohorts: ≥95% FD cohort: 3-year PFS: 88% | MRD cohort: BM-uMRD at 12 cycles: 68% FD cohort: BM-uMRD at 12 cycles: 60% |
| Kater et al13 | Ibrutinib + venetoclax vs obinutuzumab + chlorambucil | ≥65 years old or younger with CIRS >6 or CrCl <70 mL/min, without del(17p) or TP53 mutation (n = 211) | ORR 87% (CR 39%) vs 85% (CR 11%) | Estimated 3.5-year PFS: 75% vs 25% | BM-uMRD at 3 months after end of treatment: 52% vs 17% |
| Eichhorst et al8 | Ibrutinib + venetoclax + obinutuzumab | CIRS ≤6, normal CrCl, without del(17p) or TP53 mutation (n = 230) | ORR 94% (CR 62%) | 3-year PFS: 91% | PB-uMRD 15 months: 92% |
| Rogers et al28 | Ibrutinib + venetoclax + obinutuzumab | Excluded patients with known BTK cysteine 481 mutation (n = 50) | End of therapy ORR 90% | Estimated 48-month PFS: 96% | BM-uMRD at end of treatment: 67% |
| Ryan et al19 | Acalabrutinib + venetoclax + obinutuzumab | ≥18 years old No stipulation based on comorbidities or prognostic markers (n = 56; n = 29 TP53 aberrant) | ORR 98% (CR 48%) ORR TP53 aberrant: 100% (CR 52%) | NA | BM-uMRD by cycle 16: 86% BM-uMRD by cycle 16 for TP53 aberrant: 83% |
| Woyach et al29 | Acalabrutinib + venetoclax + obinutuzumab | ≥18 years old Intermediate- or high-risk CLL (n = 9) | ORR 100% (CR/CRi 50%) | Estimated 18-mo PFS: 100% | PB-uMRD at cycle 10: 75% |
| Tedeschi et al18 | Zanubrutinib + venetoclax | del(17p) (n = 36) | ORR 97% (CR/CRi 14%) | NA | NA |
| Soumerai et al20 | Zanubrutinib + venetoclax + obinutuzumab | del(17p) (n = 37) | ORR 100% (CR 57%) | Median PFS not reached at 30 months | BM-uMRD by cycle 17: 89% |
| Reference . | Regimen . | Eligibility (n) . | Response rate . | PFS . | MRD . |
|---|---|---|---|---|---|
| Jain et al9 | Ibrutinib + venetoclax | del(17p), TP53 mutation, del(11q), unmutated IGHV, or ≥65 years old (n = 120; n = 27 del(17p)/TP53 mutation) | ORR 100% (CR 88%) | 4-year PFS: 95% 4-year PFS for del(17p)/TP53 mutation: 91% | BM-uMRD at 12 cycles: 56% BM-uMRD at 24 cycles: 66% |
| CAPTIVATE10-12 | Ibrutinib + venetoclax | ≤70 years old MRD cohort (n = 164) FD cohort (n = 159) | MRD cohort: ORR 97% (CR 46%) FD cohort: ORR 96% (CR 55%) | MRD cohort: Estimated 30-month PFS for all randomized cohorts: ≥95% FD cohort: 3-year PFS: 88% | MRD cohort: BM-uMRD at 12 cycles: 68% FD cohort: BM-uMRD at 12 cycles: 60% |
| Kater et al13 | Ibrutinib + venetoclax vs obinutuzumab + chlorambucil | ≥65 years old or younger with CIRS >6 or CrCl <70 mL/min, without del(17p) or TP53 mutation (n = 211) | ORR 87% (CR 39%) vs 85% (CR 11%) | Estimated 3.5-year PFS: 75% vs 25% | BM-uMRD at 3 months after end of treatment: 52% vs 17% |
| Eichhorst et al8 | Ibrutinib + venetoclax + obinutuzumab | CIRS ≤6, normal CrCl, without del(17p) or TP53 mutation (n = 230) | ORR 94% (CR 62%) | 3-year PFS: 91% | PB-uMRD 15 months: 92% |
| Rogers et al28 | Ibrutinib + venetoclax + obinutuzumab | Excluded patients with known BTK cysteine 481 mutation (n = 50) | End of therapy ORR 90% | Estimated 48-month PFS: 96% | BM-uMRD at end of treatment: 67% |
| Ryan et al19 | Acalabrutinib + venetoclax + obinutuzumab | ≥18 years old No stipulation based on comorbidities or prognostic markers (n = 56; n = 29 TP53 aberrant) | ORR 98% (CR 48%) ORR TP53 aberrant: 100% (CR 52%) | NA | BM-uMRD by cycle 16: 86% BM-uMRD by cycle 16 for TP53 aberrant: 83% |
| Woyach et al29 | Acalabrutinib + venetoclax + obinutuzumab | ≥18 years old Intermediate- or high-risk CLL (n = 9) | ORR 100% (CR/CRi 50%) | Estimated 18-mo PFS: 100% | PB-uMRD at cycle 10: 75% |
| Tedeschi et al18 | Zanubrutinib + venetoclax | del(17p) (n = 36) | ORR 97% (CR/CRi 14%) | NA | NA |
| Soumerai et al20 | Zanubrutinib + venetoclax + obinutuzumab | del(17p) (n = 37) | ORR 100% (CR 57%) | Median PFS not reached at 30 months | BM-uMRD by cycle 17: 89% |
CRi, complete response with incomplete count recovery; FD, fixed duration.