Pilot Study of Rituximab in Refractory or Relapsed Hairy Cell Leukemia

Treatment of recurrent or nucleoside analog–refractory hairy cell leukemia (HCL) may be limited by poor tolerance (eg, interferon), profound CD4 lymphopenia, or comorbid conditions in which prolonged myelosuppression from nucleoside analog retreatment would be prohibitive. Alternative therapeutic options are needed.

Rituximab (Rituxan) is a monoclonal antibody that targets CD20, with activity in other B-cell lymphoproliferative disorders, such as low-grade lymphomas (McLaughlin P et al: J Clin Oncol 16[8]:2825-2833, 1998) and chronic lymphocytic leukemia (CLL). Mean fluorescence intensity studies reveal high CD20 expression in HCL (312 ± 110 molecules/cell) compared to CLL (65 ± 11 molecules/cell). Rituximab is also well tolerated, except for infusion-related events. We therefore investigated its activity in refractory or relapsed HCL.

From October 1998 to August 1999, 10 patients with refractory (N = 2) or relapsed (N = 8) HCL were enrolled. Rituximab was administered at a dose of 375 mg/m² weekly × 8. Median time from initial HCL diagnosis to rituximab therapy was 9 years (range, 7 months to 19 years). Median number of prior regimens was three (range, one to eight); all patients had received prior 2-chlorodeoxyadenosine (cladribine [Leustatin) therapy. Median age was 60 years (range, 23 to 74 years). Three patients were neutropenic and four were lymphopenic (absolute counts < 1.0 ×10⁹/L). Five patients had platelet counts < 100 ×10⁹/L. Median percentage of hairy cells (HCs) in the marrow was 23% (range, 7% to 71%); three patients had circulating HCs. Serum interleukin-2 (IL-2) receptor level was > 5,869 U/mL in 75% of patients. Median serum beta-microglobulin was 1.9 mg/L (range, 1.5 to 3.9 ).

Median follow-up was 4 months (range, 3 weeks to 11 months). In one patient, it was too early for response to be evaluated. Overall response rate in the nine evaluable patients (three after four doses, one after six doses, and five after all doses) was 64%; this included three complete responses (CRs); two CRs with minimal residual disease after four and eight doses, respectively; and one partial response (PR) after four doses. Three patients did not respond after four, six, and eight doses, respectively. Reductions in serum IL-2 receptor levels were observed in responders.

Infusional events with grade 1 fever/chills occurred in seven patients with the first dose; one patient developed grade 1 hypotension. Subsequent doses were generally tolerated without incident. Four patients experienced grade 1 nausea/vomiting. One patient developed grade 3 myalgias after each dose, which required narcotic analgesia. No infectious episodes were reported.

CONCLUSION: Rituximab appears promising with minimal toxicity in relapsed/refractory HCL and warrants further study. Longer follow-up is required to determine the durability of response and the optimal dosing schedule.

Click here for Dr. Bruce Cheson’s commentary on this abstract.