Table 1 Clinical trials of frontline regimens for untreated chronic lymphoid leukemia
From: Frontline therapies for untreated chronic lymphoid leukemia
Study (references) | Regimens | Age (years) | del(17p) exclusion | No. patients | Follow-up month (range) | Response (RR; 95% CI; P) | PFS | OS | Undetectable MRD rate (sensitivity, 10−4) |
|---|---|---|---|---|---|---|---|---|---|
RESONATE-2 [25] | Ibrutinib vs chlorambucil | ≥ 65 | Yes | 269 | 18.4 | ORR: 86% vs 35% (2.42; 1.91–3.07; P < 0.001) CR/CRi: 4% vs 2% | Median PFS not reached vs 18.9 months HR 0.16; 95% CI 0.09–0.28; P < 0.001 PFS rate at 18 months 90% vs 52% | Median OS not reached in either group OS rate at 24 months 98% vs 85% HR 0.16; 95% CI 0.05–0.56; P = 0.001 | Not reported |
ALLIANCE A041202 [26] | Ibrutinib vs IR vs BR | ≥ 65 | No | 547 | 38 | ORR: 93% vs 94% vs 81% CR: 7% vs 12% vs 26% | Median PFS not reported PFS rate at 24 months 87% vs 88% vs 74% HR 0.39; 0.26–0.58; P < 0.001 (BR vs I) HR 0.38; 0.25–0.59; P < 0.001 (BR vs IR) HR 1.00; 0.62–1.62; P = 0.49 (IR vs I) | Median OS not reported OS rate at 24 months 90% vs 94% vs 95% P ≥ 0.65 for all pairwise comparisons | In bone marrow: 1% vs 4% vs 8% (after 9 cycles) |
ECOG E1912 [28] | IR vs FCR | 18–70 | Yes | 529 | 33.4 | Not reported | Median PFS HR 0.35; 0.22–0.5; P < 0.001 PFS rate not reported | Median OS HR 0.17; .05–0.54; P < 0.003 OS rate not reported | Not reported |
iLLUMINATE [30] | IO vs CO | IO: 70 (66 to 75); CO: 72 (66–77) | No | 229 | 31.3 (29.4–33.2) | ORR: 88% vs 73% (1.21; 1.06–1.37; P = 0.0035) CR/CRi: 22% vs 8% (2.51; 1.21–5.21; P = 0.0096) | Median PFS not reached vs 19.0 months (15.1–22.1) HR 0.23; 0.15–0.37; P < 0.0001 PFS rate at 30 months 79% vs 31% | Median OS not reached in either group HR 0.92; 0.48–1.77 OS rate at 30 months 86% vs 85% | In peripheral blood: 20% vs 30% In bone marrow: 17% vs 20% |
Ibrutinib plus venetoclax [31] | Ibrutinib plus venetoclax | 65 (26–83) | No | 80 | 14.8 | CR/CRi: 88% (after 12 cycles) | Median PFS not reported PFS rate at 12 months 98%; 95% CI 94–100 | Median OS not reported OS rate at 12 months 99%; 95% CI 96–100 | In bone marrow: 61% (after 12 cycles) |
CLL14 [32] | VO vs CO | 72 (41–89) | No | 432 | 28.1 | ORR: 84.7% vs 71.3% (P < 0.001) CR: 49.5% vs 23.1% (P < 0.001) | Median PFS not reported PFS rate at 24 months 88.2% vs 64.1% | Median OS not reached in either group OS rate at 24 months 91.8% vs 93.3% HR 1.24; 0.64–2.40; P = 0.52 | In peripheral blood: 75.5% vs 35.2%; P < 0.001 In bone marrow: 56.9% vs 17.1%; P < 0.001 (3 months after treatment completion) |
CLL10 [38] | BR vs FCR | FCR: 62.1 (55–67); BR: 61 (54–69) | Yes | 561 | 37.1 (31.0–45.5) | ORR: 96% vs 95% (P = 1.0) CR: 31% vs 40% (P = 0.034) | Median PFS 41.7 months vs 55.2 months HR 1.643; 90.4% CI 1.308–2.064 | Median OS not reported OS rate at 36 months 92% vs 91% HR 1.034; 0.620–1.724; P = 0.89 | In peripheral blood: 38% vs 49%; P = 0.041 In bone marrow: 11% vs 27%; P < 0.001 |