Bendamustine and Rituximab in Relapsed and Refractory Hairy Cell Leukemia

Abstract

Purpose To determine tolerability and for the first time explore efficacy of bendamustine plus rituximab (BR) in multiply relapsed/refractory hairy cell leukemia (HCL), using 2 different dose levels of bendamustine. Experimental design HCL patients with ≥2 prior therapies requiring treatment received rituximab 375 mg/m2 days 1 and 15, plus bendamustine 70 (n=6) or 90 (n=6) mg/m2, days 1 and 2, for 6 cycles at 4-week intervals. Results At 70 and 90 mg/m2/dose of bendamustine, overall response rate was 100%, with 3 (50%) and 4 (67%) complete remissions (CR) in each respective group. Minimal residual disease (MRD) was absent in 67% and 100% of CRs, respectively. All 6 without MRD remain in CR at 30–35 (median 31) months of follow-up. Soluble CD22 and CD25 levels decreased with all responses, with median values decreasing from 17.7 and 42 ng/ml at baseline to undetectable and 2 ng/ml after CR, respectively (p<0.001). Of 12 patients receiving 72 cycles of BR, the most common toxicities were hematologic, including thrombocytopenia (83%), lymphopenia (75%), leukopenia (58%) and neutropenia (42%). Grade 3–4 hematologic toxicity included lymphopenia and thrombocytopenia (each 75%), leukopenia (58%), and neutropenia (25%). No significant dose-related differences were detected in response or toxicity. Conclusion BR has significant activity in HCL. Bendamustine at either 70 or 90 mg/m2/dose was highly effective in multiply relapsed/refractory HCL, and could be considered for achieving durable CRs without MRD in patients after failure of standard therapies. Since it was not dose-limiting, 90 mg/m2/dose was chosen for future testing.

Consensus guidelines for the diagnosis and management of patients with classic hairy cell leukemia

“…72,73 There are many opportunities for evaluating novel agents alone or in strategic combinations. 74 Because we have prolonged the projected survival for these patients, recurrent relapse can be anticipated, which merits continued investigation.…”

Hairy cell leukemia 2018: Update on diagnosis, risk‐stratification, and treatment

“…Especially in the case of multiply relapsed/refractory HCL, the combination of bendamustine at 70–90 mg/m 2 /dose with rituximab has demonstrated significant activity 47. This regimen should also be considered in cases in which novel agents that were previously described are not available.…”

Novel therapeutic options for relapsed hairy cell leukemia

“…In another study, bendamustine was combined with rituximab in 12 patients with heavily pretreated multiply relapsed HCL [31]. CR was achieved in about 60% of patients; one patient who achieved a CR relapsed after a median follow-up of 35 months [32]. Although initial results of the combination of rituximab with purine analogs are encouraging, longer follow-up is required to estimate whether this strategy can achieve cure in HCL.…”