Phase II Study of Rituximab in the Treatment of Cladribine-Failed Patients With Hairy Cell Leukemia

March 1, 2002

Hairy cell leukemia (HCL) is an indolent B-cell neoplasm that strongly expresses CD20. Despite initial very high response rates with cladribine (Leustatin), many patients ultimately relapse.

Hairy cell leukemia (HCL) is an indolent B-cell neoplasm that stronglyexpresses CD20. Despite initial very high response rates with cladribine(Leustatin), many patients ultimately relapse.

From January 2000 to February 2001, 16 patients (15 male, 1 female) with HCL,with a median age of 57 years (range: 38-81 years), having relapsed afterprior treatment with cladribine, were treated with rituximab (Rituxan) at 375mg/m² weekly × 4. All patients had received at least one prior course ofcladribine (median: 44 months from last cladribine; range: 19-119 months),eight patients received two prior courses of cladribine, five patients receivedinterferon, and two patients had undergone splenectomy.

A total of 15 patients are currently evaluable for response, with at least a6-month follow-up. Three patients (20%) achieved complete remissions, defined asthe absence of hairy cells in the peripheral blood and bone marrow with thefollowing peripheral blood parameters: ³ 1.5 × 109 neutrophils/mL, hemoglobinconcentration ³ 12 g/dL, and ³ 100,000 platelets/mL. One patient (7%) hadminimal residual disease as evidenced by positive staining on DBA.44 and CD20without morphologic evidence of HCL by light microscopy. One patient (7%)achieved a partial response, defined as at least 50% improvement in allcytopenias with at least a 50% reduction of hairy cells from the peripheralblood and bone marrow. Thus, 5 of 15 (33%) patients achieved a response. At amedian follow-up of 12 months (range: 9-20 months), no responders hadrelapsed. Three patients (20%) achieved hematologic improvement withoutsufficient reduction in marrow HCL cells to qualify as a response; both lastedless than 3 months in duration.

The only grade 3/4 toxicities demonstrated were culture-negative febrileneutropenia, transient and reversible disseminated intravascular coagulationrelated to rituximab administration, and a diverticular abscess. Of 10 patientswho failed to respond, 6 subsequently received other treatments: 3 wereretreated with cladribine, 2 underwent splenectomy, and 1 received pentostatin(Nipent). All six patients treated after rituximab achieved hematologicimprovements, although no bone marrow follow-up data are presently available.

CONCLUSION: Rituximab, administered at this dose and schedule, has onlymodest activity in cladribine-failed HCL patients when compared to other agentsactive in this disease.

Click here to read Dr. Bruce Cheson's commentary on this abstract.