Table 3.
Efficacy of BTK inhibitors in chronic lymphocytic leukaemia/small lymphocytic lymphoma in phase III trials
| Trial | Treatmenta (no. of pts) | Med. follow-up (mo.) | Med. PFSb (mo.) | Med OS (mo.) | ORR (%) |
|---|---|---|---|---|---|
| In relapsed/refractory disease | |||||
| RESONATE | IBR (195) vs OFA (196) | 9.4 [65] | NR vs 8.1** | NR vs NR* | 43 vs 4** |
| 65.3 vs 65.6 [64] | 44.1 vs 8.1** | 67.7 vs 65.1 | |||
| ASCEND | ACA (155) vs investigator’s choice [IDE + RTX (119) or B/R (36)] | 16.1 [67] | NR vs 16.5*** | NR vs NR | 81 vs 75 |
| ELEVATE-RR | ACA (268) vs IBR (265) | 40.9 [68] | 38.4 vs 38.4c | NR vs NR | 81 vs 77 |
| ALPINEd | ZAN (207) vs IBR (208) | 15 [69] | 94.9 vs 84.0e** | 78.3 vs 62.5** | |
| HELIOS | IBR + B/R (289) vs PL + B/R (289) | 17 [71] | NR vs 13.3** | NR vs NR | 83 vs 68*** |
| 63.7 [72] | 65.1 vs 14.3*** | NR vs NR** | |||
| In treatment-naïve patients | |||||
| RESONATE-2 | IBR (136) vs CLB (133) | 18.4 [73] | NR vs 18.9** | NR vs NR** | 82 vs 35** |
| 60 [74] | NR vs 15** | NR vs NR | |||
| iLLUMINATE | IBR + OBZ (113) vs CLB + OBZ (116) | 31.3 [75] | NR vs 19.0*** | NR vs NR | 88 vs 73* |
| ELEVATE-TN | ACA + OBZ (179) vs OBZ + CLB (177) | 28.3 [27] | NR vs 22.6*** | NR vs NR | 94 vs 79*** |
| 46.9 [76] | NR vs27.8*** | NR vs NR | 96.1 vs 82.5*** | ||
| ACA (179) vs OBZ + CLB (177) | 28.3 [27] | NR vs 22.6*** | NR vs NR | 86 vs 79 | |
| 46.9 [76] | NR vs 27.8*** | NR vs NR | 89.9 vs 82.5* | ||
| Alliance 041202 | IBR + RTX (182) vs B/R (183) | 38 [77] | NR vs 43 | ||
| IBR (182) vs B/R (183) | 38 [77] | NR vs 43 | |||
| IBR + RTX (182) vs IBR (182) | 38 [77] | NR vs NR | |||
| E1912 | IBR + RTX (354) vs FCR CIT (175) | 33.6 [78] | 89.4 vs 72.9f** | 98.8 vs 91.5f** | |
ACA acalabrutinib, B/R bendamustine plus rituximab, BTK Bruton tyrosine kinase, CLB chlorambucil, FCR CIT fludarabine, cyclophosphamide and rituximab chemoimmunotherapy, IBR ibrutinib, IDE idelalisib, med. median, mo. month(s), NR not reached, OBZ obinutuzumab, OFA ofatumumab, ORR overall response rate, OS overall survival, PFS progression-free survival, PL placebo, pts patients, RTX rituximab
*p < 0.05, **p ≤ 0.001, p < 0.0001 treatment 1 vs treatment 2
aAssigned treatment at study drug initiation; crossover was permitted in some trials following disease progression
bIn general, initial results are as assessed by an independent review committee; later results are investigator-assessed
cNon-inferiority of ACA to IBR demonstrated
dData presented are from a prespecified interim analysis for the first 415 pts enrolled
e12-mo. PFS rates
f3-year rates