First-Line Treatment of Hairy Cell Leukemia with Cladribine Followed by Rituximab Consolidation Significantly Improves Leukemia-Free Survival

Context Purine analogue therapy remains the standard of care in hairy cell leukemia (HCL) management. Despite high remission rates, many patients subsequently relapse and require re-treatments. Objective The aim of this study is to compare the effectiveness and safety of cladribine vs. cladribine followed by rituximab consolidation as first-line therapy of HCL. Design This is a retrospective study including all consecutive patients with classical HCL treated and followed at the American University of Beirut Medical Center (AUBMC) between 2000 and 2019. Methods We identified 29 HCL patients, with a median age of 50.5 (range: 30–71) years. Patients were divided into two cohorts based on treatment received: cohort A (N=14) received cladribine 5.6 mg/m2 intravenously (IV) for 7 days as a single agent, and cohort B (N=15) received the same dose of cladribine followed by rituximab 375 mg/m2 IV weekly for eight doses. Rituximab consolidation was given after a median time of 33 days (17–60 days) from cladribine completion. Complete remission rates were 64% and 100% in cohorts A and B, respectively. In cohort A, seven (50%) patients relapsed after a median duration of 48 months (range: 1–209 months), requiring second-line treatment with cladribine followed by rituximab. In cohort B, no relapses occurred. After a median follow up of 67 months (range: 1–227 months), the 5-year disease-free survival was significantly better in group B (100%) compared to group A (58%) (HR=0.16, 95% CI: 0.032–0.84, p=0.03). There was no significant difference in overall survival between the two groups. Grade 3/4 adverse events were observed in 92%% and 80% of patients in cohorts A and B, respectively, mainly neutropenia (78.5% vs 66.6%) and febrile neutropenia (71% vs. 40%). One patient in cohort B who received rituximab consolidation too early (day 17) died from febrile neutropenia and septic shock. Conclusion Consolidation rituximab after cladribine in frontline treatment of classical HCL showed high response rate of 100% and translated into a significant improvement in disease-free survival. Cladribine followed by rituximab consolidation may be considered as standard first-line therapy of HCL.