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Rituximab plus bendamustine or chlorambucil in CLL
Colony-stimulating factors were taken more frequently by patients treated with R-B (111/178 [62.4%] vs. 71/179 [39.7%] for R-Clb). ECOG performance status scores were ≥1 in approximately half the study population. At base- line, 108/177 (61.0%), 56/177 (31.6%) and 4/177 (2.3%) patients treated with R-B, and 102/178 (57.3%), 60/178 (33.7%) and 3/178 (1.7%) patients treated with R-Clb had normal; abnormal, non-clinically significant; and abnor- mal clinically significant calculated creatinine clearance, respectively.
Efficacy
In 1L patients, the CR rate after C6 was higher with R- B versus R-Clb (24% [n=29/121] vs. 9% [n=11/120];
P=0.002; Table 2). Logistic regression analysis supported the R-B treatment effect after adjusting for baseline covari- ates (odds ratio 4.18, 95% CI 1.77-9.87; P=0.001). None of the covariates had a statistically significant impact on the CR rate.
ORRs (based on the investigator’s assessment) at the end of rituximab treatment were similar for R-B and R-Clb (91% vs. 86%; P=0.304). The proportion of patients with stable disease (3% vs. 6%) and progressive disease (3% vs. 2%) at the end of treatment were also similar for R-B vs. R-Clb, respectively.
A statistically significant ten-month extension in medi- an PFS was observed with R-B versus R-Clb (39.6 vs. 29.9 months; HR [adjusted for baseline Binet stage] 0.523, 95%
Figure 1. Patient disposition. Numbers in parentheses represent the number of patients from the 1L subpopulation. In total, 118 patients (33%) discontinued the study prematurely, due to death (R-B 16%; R-Clb 19%), patient lost to follow-up (3% per arm), investigator decision (R-B 2%; R-Clb 3%), patient withdrew consent (R-B 3%; R-Clb 2%), patient non-compliance (R-B 1%; R-Clb 2%), and ‘other’ reasons (R-B 6%; R-Clb 7%). Reason for withdrawal was not available for one patient (R-Clb). AE: adverse event; C: cycle; N: number of patients; PD: progressive disease; R-B: rituximab plus bendamustine; R-Clb: rituximab plus chlorambucil.
Table 2. CR and PRs at C6 in 1L patients. Assessment
CR confirmed by BM biopsya
PR based on the investigator’s assessment
Analysis
CR
Logistic regressionc
PR
N
n (%) P-valueb
N
OR (95% CI) P-valued
N
n (%)
R-B
121 29 (24)
113
121
60 (50)
0.002
4.18 (1.77-9.87) 0.001
R-Clb
120 11 (9)
103
120
79 (66)
aCRs confirmed by BM biopsy only were included.bP-value is based on a one-sided continuity corrected χ2 test.cThe following covariates were included in the logistic regression: Binet stage (A and B vs. C); IGVH mutational status (mutated vs. unmutated); 17p/11q deletion (heterozygote deletion vs. normal); ECOG PS (0 vs. ≥1). dP-value is based on the Wald test. BM: bone marrow; CI: confidence interval; CR: complete response; OR: odds ratio; PR: partial response; R-B: rituximab plus bendamustine; R-Clb: rituximab plus chlo- rambucil.
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