Skip to main content

Advertisement

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
  1. I ibrutinib, BR bendamustine rituximab, IR ibrutinib rituximab, VO venetoclax obinutuzumab, CO chlorambucil obinutuzumab, FCR fludarabine cyclophosphamide rituximab, CR complete remission, OS overall survival, PFS progression free survival, ORR overall response rate, MRD minimal residual disease