Patients type | Treatment regimen | Efficacy | Study | Phase | N |
---|---|---|---|---|---|
Non-GCB | |||||
TN | Ibrutinib + R-CHOP (rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2, and oral prednisone [or equivalent] 100 mg) vs. placebo + R-CHOP | 36-month PFS rate: 70.8% vs. 68.1%; 36-month OS rate: 82.8% vs. 81.4%; CR rate: 67.3% v 68.0% | PHOENIX [79] | 3 | 419 vs. 419 |
TN, ≤ 65 years | Acalabrutinib + R-CHOP | Ongoing | ESCALADE [80] | 3 | 600 |
R/R | Zanubrutinib | ORR, non-GCB: 36%, GCB: 25% | BGB-3111–207 [83] | 2 | 29 |
R/R, ASCT ineligible | Zanubrutinib + lenalidomide | Best ORR: 90.9%, CR: 36.4% Study ongoing | BGB-3111–110 [84] | 1 | 27 |
R/R | Ibrutinib | ORR, non-GCB: 37%, GCB: 5% | NCT00849654 NCT01325701 [85] | 2 | 80 |
R/R | Acalabrutinib | ORR, non-GCB: 24% (5/21); 4 CR and 1 PR | NCT02112526 [86] | 1b | 21 |
BCL2/MYC expression | |||||
TN | Ibrutinib + R-CHOP | DE: CR: 67.5%; PR 22.8% | PHOENIX, post hoc [174] | 3 | 200 |
R/R | Ibrutinib | DE: ORR 47%; CR 37% | Landsburg et al. [90] | Case-series | 25 |
R/R | Zanubrutinib | DE: ORR 61%; NDE: ORR 29% | BGB-3111–207 [83] | Post-hoc | 121 |
TN | Zanubrutinib + R-CHOP | Ongoing | NCT05189197 [92] | 2 | 41 |
CD79B, MYD88 (MCD) | |||||
TN | Ibrutinib + R-CHOP | MCD and aged ≤ 60 years: 3-year EFS and OS: 100% | PHOENIX, post hoc [94] | 3 | 31 |
TN | Orelabrutinib + R-CHOP | Ongoing | NCT05234684 [95] | 3 | 150 |
R/R | Zanubrutinib | CD79B mutation: ORR 46%; MYD88 mutation: ORR 40%; MYD88 + CD79B (MCD) mutation: ORR 50% | BGB-3111–207 [83] | 2 | 41 |
Elderly and unfit/frail | |||||
TN | Ibrutinib + rituximab + lenalidomide | ORR 66.7%; CR rate: 56.7%; 2-year PFS rate: 53·3%; 2-year OS rate: 66·7% | NCT03949062 [99] | 2 | 30 |
TN | Zanubrutinib + rituximab + lenalidomide vs. R-mini-CHOP (rituximab 375 mg/m2 on day 1, cyclophosphamide 400 mg/m2, doxorubicin 25 mg/m2, and vincristine 1 mg on day 2, and prednisone 40 mg/m2 on days 2–6, every 21 days) | Ongoing | NCT05179733 [100] | 3 | 280 |