Long-term results of the sequential combination of cladribine and rituximab in Hairy cell leukemia

Abstract

We report on the long-term efficacy and safety of a phase 2 trial of sequential cladribine and rituximab in hairy cell leukemia (HCL). One-hundred and thirty-nine patients were enrolled: 111 in the frontline setting, 18 in first relapse, and 10 with variant HCL (HCLv). A complete response (CR) was achieved in 133 of 137 evaluable participants (97%) with measurable residual disease (MRD) negativity in 102 (77%). MRD status was not associated with significant differences in event-free survival (EFS) or overall survival (OS). With a median follow-up of 7.8 years (range: 0.40-18.8), eight patients have experienced disease relapse (5.8%), 4/111 with newly diagnosed HCL (3·6%) and 4/10 with HCLv (40%) (p = 0.002). The 10-year EFS and OS rates were 86.7% and 91.1%, respectively. Grade 3 adverse events were observed in 28 participants (20·1%), mostly due to infections. Treatment of HCL with sequential cladribine followed by rituximab is associated with excellent efficacy and safety results both in the frontline and relapsed settings.

Keywords: HCL; HCLv; cladribine; clinical trial; rituximab.

Figure 1.. Primary outcomes of study cohort.

(A) Bar graph of best response by disease type. PR = partial response, CRi = complete response with incomplete count recovery, CR = complete response. (B) and (C) Kaplan-Meier curves for event free and overall survival, respectively. Censored observations are marked.

Figure 2.. Measurable residual disease (MRD) at best response.

MRD was measured by multiparameter flow cytometry (FCM) on bone marrow specimens. (A) Boxplot depicting percentage of hairy cells over time. Different letters represent groups that are statistically different from one another. (B) Bar graph of the percentage of patients with positive or negative MRD at time of best response separated by classical and variant HCL as well as relapse status. (C) and (D) represent Kaplan-Meier curves for event free and overall survival in patients with classical HCL based on MRD at best response. Censored observations are marked.

Figure 3.. Peripheral blood MRD has good concordance with bone marrow MRD.

MRD was measured by multiparameter flow cytometry (FCM) on both bone marrow (BM) and peripheral blood (PB) specimens at specified time points. (A) Linear regression and Pearson’s correlation between BM and PB samples at HCL diagnosis. (B) Percentage of patients in remission with positive MRD by PB by year from treatment initiation.