Table 4.
Summary of time-limited frontline trials
| Reference | Trial | Patients | Primary end point | Results |
|---|---|---|---|---|
| Randomized phase 3 trials | ||||
| Shanafelt et al17, ECOG1912 |
FCR vs I-R | Age <70 no del 17p N = 529 |
PFS FU: 33.6 mo |
I - R > FCR (89.4% vs 72.9% at 3 y; HR: 0.35; 95% CI, 0.22-0.56; P < .001) OS: I - R > FCR (98.8% vs 91.5% at 3 y) HR: 0.17; 95% CI, 0.05-0.54; P < .001 |
| Al-Sawaf et al3, CLL14 |
CLB-O vs VEN-O | CIRS >6 and/or Cl. creat 30-69 mL/min N = 432 |
PFS FU: 39.6 mo |
VEN-O > CLB-O (NE vs 35.5 mo) HR: 0.31, 95% CI, 0.22–0.44; P < .0001 |
| Woyach et al1, ALLIANCE | BR/I-R/I | Age >65 N = 447 |
PFS FU: 38 mo |
I-R > BR. HR: 0.38; 95% CI, 0.25-0.59; P < .001 I > BR. HR: 0.39; 95% CI, 0.26-0.58; P < .001 |
| Kater et al23, GLOW |
VEN-I/CLB-O | Age >65 or CIRS >6 or Cl. creat <70 mL/min N = 211 |
PFS FU: 27.7 mo |
VEN-I > CLB-O HR: 0.216 (95% CI, 0.131-0.357); p < .0001) |
| Phase 2 trials | ||||
| Michallet et al24, ICLL07 | I-O+/−4 courses FCO-I | Fit patients, no del 17p or p53 N = 135 |
CR + BM MRD <0.01% FU: 26.3 |
CR + MRD <0.01%: 62% (95% CI 55% to 69%) |
| Davids et al25 | FCR 6 courses-I (stop 2 y if BM uMRD) | Age <65 N = 85 |
CR + BM uMRD 2 mo post FCR FU: 16.5 mo |
CR + BM uMRD: 33%, (95% CI 23-44%) |
| Jain et al27 | VEN-I | Del17P and/or TP53 mut and/or del11q and/or U-IGHV and/or age >65 N = 80 |
CR + CRi FU: 14.8 mo |
CR + CRi: 88%, CR + uMRD: 61% |
| Wierda et al28, CAPTIVATE | VEN-I uMRD : I vs placebo MRD+ : I vs V-I |
Age <70 N = 164 |
1 y DFS FU: NA |
I vs placebo: NS (95% vs 100%) 30-mo PFS ∼95% in all arms |
A, acalabrutinib; B, bendamustine; C, Cyclophosphamide; Cl. creat, clearing of creatine; CR, complete remission; DFS, disease-free survival; F, Fludarabine; FU, median follow-up; I, ibrutinib; NA, not applicable; NE, not evaluable; NS, not significant; O, obinutuzumab; OS, overall survival; PFS, progression-free survival; R, rituximab; VEN, venetoclax.