Table 2.
Phase 3 clinical trials of BTK inhibitors in relapsed/refractory chronic lymphocytic leukemia.
| Study | Treatment | Patients, N |
Median Age [years] | Median Follow-Up [months] |
ORR (CR) | Median PFS | Median OS | Discontinu Ation Rates |
|---|---|---|---|---|---|---|---|---|
| Byrd et al. [33] Munir et al. [34] (RESONATE) |
Ibrutinib vs. Ofatumumab |
195 vs. 196 | 67 vs. 67 | 41 | 91% (21%) vs. 82% (11%) | 44.1 m vs. 8.1 m (p ˂ 0.0001) |
67.7 m vs. 65.1 m HR = 0.810 |
16% for ibrutinib |
| Fraser et al. [39] (HELIOS) | Ibrutinib + BR vs. BR |
289 vs. 289 |
64 vs. 63 |
34.8 | 87% (38%) vs. 66% (8%) | NR vs. 13.3 m, p < 0.0001 |
NR vs. NR, p = 0.0598 |
24% vs. 45% |
| Sharman et al. [41] (GENUINE) |
Ibrutinib + Ublituximab vs. Ibrutinib |
64 vs. 62 |
66 vs. 67 | 41.6 | 83% (17%) vs. 65% (3%) |
NR vs. 35·9 m p = 0.016 |
NR vs. NR, p = 0.12 |
15% vs. 12% |
| Byrd et al. [16] (ELEVATE RR) | Acalabrutinib vs. Ibrutinib |
268 vs. 265 |
66 vs. 65 | 31.3 | 81.0% (NA) vs. 77% (NA) |
38.4 vs. 38.4 p ˂ 0.001 |
NR vs. NR HR, 0.82 |
14.7% vs. 21.3% |
| Ghia et al. [42] (ASCEND) | Acalabrutinib vs. IR or BR |
155 vs. 155 |
65 vs. 67 | 40.9 | 81% (0%) vs. 75% (1%) |
NR vs. 16.5 m p < 0.0001 |
89% vs. 80% at 1 y p < 0.0001). |
14.7% vs. 21% |
| Hillmen et al. [17] ALPINE |
Zanubrutinib vs. Ibrutinib |
Total 415 | 66 vs. 65 | 15 | 76% (NA) vs. 64%(NA) | 94.9% vs. 84% at 1 y p < 0.0007 |
97% vs. 93% at 1 y | 7.8% vs. 13.0% |
Abbreviations: BR—Bendamustine and rituximab, FCR—fludarabine, cyclophosphamide and rituximab, HR—hazard ratio, IR—idelalisib + rituximab, m—months, N—number of patients, CR—complete remission, PFS—progression free survival, R—rituximab, NA—not available, NR—not reached, O—obinutuzumab, OS—overall survival, R—rituximab, y—year.