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Rituximab plus bendamustine or chlorambucil in CLL
A
B
Figure 2. Efficacy in 1L patients. (A) PFS and (B) OS. CI: confidence interval; HR: hazard ratio; NR: not reached; OS: overall survival; PFS: progression-free survival; R-B: rituximab plus bendamustine; R-Clb: rituximab plus chlorambucil.
mg/m2; CLL11, 0.5 mg/kg), which resulted in a higher median cumulative dose (MABLE, 720 mg; CLL11, 366- 400 mg), and differences in the study populations, with patients in MABLE having fewer active comorbidities than those in CLL11 (medians of 3 and 5, respectively) and a better performance status.10 Earlier phase II studies in elderly CLL patients treated 1L with R-Clb reported CR rates of 10-17% and ORRs of 82-84%.8,9 The CLL2M trial, a phase II study of CLL patients treated 1L with R-B, at the same B dosage as the current study, reported a CR rate of 23% and an ORR of 88%.7
In 1L patients in the study reported herein, the median PFS of 39.6 months in the R-B arm was significantly longer (by 10 months) than the value in the R-Clb arm. This result is similar to the median PFS of 43.2 months achieved in fit CLL patients treated with R-B in the CLL10 study,18 and is consistent with the findings of the CLL2M study, which enrolled fit and unfit 1L patients and report- ed a median event-free survival in R-B-treated patients of 33.9 months.7 The CLL2M study did not select patients by fitness, but a substantial proportion could be considered unfit based on age, Binet stage, and renal impairment.7 In MABLE, 33% of the 1L patients were Binet stage C and the median age was 72 years. The PFS result in the R-Clb arm in MABLE was almost twice as long as that in CLL11 (29.9 vs. 15.4 months),11 however, as noted above, a direct comparison of these studies is limited by differences in Clb doses and patient fitness.
In MABLE, 1L patients with CR had higher MRD-nega- tivity rates with R-B versus R-Clb, indicating a greater depth of response with R-B. Of note, MRD was assessed primarily in BM from patients with CR based on the investigator’s assessment, whereas in CLL11 and previous phase II studies, MRD was measured in peripheral blood ([PB] or BM) from all patients.7,8,10 One phase II study reported a MRD-negativity rate of 12.5% (2/16 patients) using BM aspirates from R-Clb-treated patients who achieved a CR/unconfirmed CR.9
Median OS was not significantly different between treatment arms in 1L patients in MABLE and was not reached in previous phase II studies of R-B and R-Clb,7-9 or in the CLL11 and COMPLEMENT-1 studies.11,19 At current follow-up reported for CLL11 and COMPLEMENT-1, no significant OS benefit was observed for G-Clb versus R-Clb or ofatumumab plus Clb (Ofa-Clb) versus Clb, respectively,11,19 whereas a significant improvement was observed for G-Clb versus Clb alone.10 Further observation is required to determine if there is an OS benefit with G-Clb versus R-Clb or Ofa-Clb versus Clb.
Safety profiles (for pooled 1L and 2L patients) were sim- ilar for R-Clb and R-B, with no new or clinically relevant safety signals, and events were as expected for CLL patients receiving immunochemotherapy.7-9 Incidences of all-grade AEs, SAEs, and treatment-related AEs were sim- ilar across arms. Grade ≥3 AE incidence was slightly high- er with R-B versus R-Clb, driven by a higher incidence of
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