Phase 2 study of cladribine followed by rituximab in patients with hairy cell leukemia

Abstract

We conducted this study to determine the feasibility and safety of cladribine followed by rituximab in patients with hairy cell leukemia including the vari-ant form (HCLv). Cladribine 5.6 mg/m² given IV over 2 hours daily for 5 days was followed ∼ 1 month later with rituximab 375 mg/m² IV weekly for 8 weeks. Responses were recorded and BM minimal residual disease (MRD) was evaluated after the completion of rituximab. Thirty-six patients have been treated including 5 with HCLv. Median age was 57 years (range, 37-89). All patients (100%) have achieved complete response (CR), defined as presence of no hairy cells in BM and blood with normalization of counts (absolute neutrophil count [ANC]> 1.5 × 10⁹/L, hemoglobin [Hgb] > 12.0 g/dL, platelets [PLT] > 100 × 10⁹/L), as well as resolution of splenomegaly. There were no grade 3 or 4 nonhematologic adverse events directly related to the treatment. Only 1 patient (with HCLv) has relapsed; median CR duration has not been reached (range,1+-63+ months). Three patients with HCLv died including 1 with relapsed disease and 2 from unrelated malignancies. Median survival duration has not been reached (range, 2+-64+ months). Treatment with cladribine followed by rituximab is effective tk;4and may increase CR rate. This study was registered at www.clinicaltrials.gov as NCT00412594.

Figure 1

Outcome after treatment. (A) Complete remission duration. (B) Overall survival by subgroup.

Figure 2

Monitoring MRD. (A) MRD by multiparameter flow cytometry (MFC) for patients with classic hairy cell leukemia (n = 31). Testing on the first 3 time points was done on BM specimens and the rest on peripheral blood. (B) MRD by IgH PCR for patients with classic hairy cell leukemia (n = 31; testing not done for all patients at diagnosis). The results for MFC and PCR at various time points do not always belong to the same patients because of sample inadequacy or lack of testing. MRD evaluations for patients with HCLv were not included in these figures.

Figure 3

Serum IL-2R levels (units per milliliter) before and after therapy in patients with hairy cell leukemia (n = 26).

Figure 4

Immune function parameters. (A) Median absolute CD4 and CD8 counts (cells per microliter) before and after therapy. (B) Ig levels (milligrams per deciliter) pre- and posttherapy.