Long‐term durable remission by cladribine followed by rituximab in patients with hairy cell leukaemia: update of a phase II trial

Abstract

Summary Nucleoside analogues are highly active in patients with hairy cell leukaemia (HCL); however, patients continue to relapse. This phase II study evaluated the efficacy and safety of cladribine followed by rituximab in patients with untreated HCL (N=59), relapsed HCL (N=14) and HCL variant (HCLv, N=7). Cladribine 5.6 mg/m2 was given intravenously (IV) daily for 5 days and was followed approximately 1 month later with rituximab 375 mg/m2 IV weekly for 8 weeks. Complete response rate in patients with untreated HCL, relapsed HCL and HCLv was 100%, 100% and 86%, respectively. With a median follow up of 60 months, 5-year failure-free survival (FFS) in patients with untreated HCL, relapsed HCL and HCLv was 95%, 100% and 64%, respectively. Median duration of response to the cladribine followed by rituximab was significantly longer than the first-line cladribine single agent in patients who received this treatment as second-line treatment (72 months vs not reached, P=0.004). Almost all patients (94%) achieved negative minimal residual disease (MRD) after the treatment. Positive MRD during the follow up did not necessarily result in clinically relevant relapse. Cladribine followed by rituximab is highly effective even in patients with relapsed disease and HCLv, and can achieve durable remission.

Hairy Cell Leukemia, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology

“…In a phase II study that evaluated cladribine followed by rituximab in patients with previously untreated and relapsed HCL, undetectable MRD status was achieved in 94% of patients at the end of treatment. 46 However, MRD-positivity during follow-up did not necessarily result in clinically relevant risk for relapse.…”

“…46,47 In a phase II study that included 14 patients with relapsed HCL, cladribine followed by rituximab resulted in a CR rate of 100%. 46 After a median follow-up of 60 months, 5-year FFS and OS rates were 100%.…”

“…46,47 In a phase II study that included 14 patients with relapsed HCL, cladribine followed by rituximab resulted in a CR rate of 100%. 46 After a median follow-up of 60 months, 5-year FFS and OS rates were 100%. In a retrospective study of 18 patients with pretreated HCL relapsing after purine analogue monotherapy (median of 2 prior therapies), rituximab in combination with pentostatin or cladribine resulted in a CR rate of 89%.…”

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

“…Indeed, in a prospective study including 59 untreated patients, 14 relapsed HCL patients and 7 HCL‐V patients, the 5‐year failure‐free survival was 95%, 100% and 64% with cladribine, respectively, after which, one month later, rituximab 375 mg/m 2 was administered weekly for 8 weeks 36. Furthermore, 59 patients (74%) achieved a negative MRD: 76% in untreated patients, 64% in relapsed patients and 71% in HCL‐V patients.…”

“…A first‐line option relies on the association of cladribine with rituximab, combined49 or with a sequential scheme 36. The same scheme could be followed in relapse cases.…”