Rituximab combined with cladribine or with cladribine and cyclophosphamide in heavily pretreated patients with indolent lymphoproliferative disorders and mantle cell lymphoma

Abstract

BACKGROUND In vitro studies have shown synergistic or additive interactions between rituximab and purine nucleoside analogues. The results of recent clinical trials seem to confirm these preclinical observations. METHODS For the current study, the authors evaluated the feasibility, efficacy, and toxicity of combined regimens that consisted of either rituximab plus cladribine (2‐CdA) (the RC regimen) or RC plus cyclophosphamide (the RCC regimen) in the treatment of patients with heavily pretreated, indolent lymphoid malignancies. Fifty‐four adult patients with recurrent or refractory, low‐grade non‐Hodgkin lymphoma (LG‐NHL) and B‐cell chronic lymphocytic leukemia (B‐CLL) were treated according to the RC/RCC regimens. The RC protocol consisted of intravenous rituximab at a dose of 375 mg/m² on Day 1 and 2‐CdA at a dose of .12 mg/kg per day on Days 2 through 6. The RCC protocol consisted of rituximab at a dose of 375 mg/m² on Day 1, 2‐CdA at a dose of 0.12 mg/m² on Days 2 through 4, and intravenous cyclophosphamide at a dose of 250 mg/m² per day on Days 2 to 4. The RC/RCC courses were repeated at 4‐week intervals. RESULTS Thirty‐three patients with B‐CLL, 12 patients with LG‐NHL and 9 patients with mantle cell lymphoma (MCL) entered the study. Thirty‐three patients (61%) had recurrent disease after prior therapy, and 21 patients (39%) had refractory disease. Thirty‐one patients were treated on the RC regimen, and 23 patients were treated on the RCC regimen. Six patients (11%) achieved a complete response, and 33 patients (60%) achieved a partial response. The median failure‐free survival of responders was 10.5 months. The treatment revealed tolerability, with episodes of severe neutropenia (Grade 3 and 4 [according to World Health Organization criteria]) observed in 6 patients (11%), episodes of Grade 3 and 4 infections observed in 11 patients (20%), and episodes of Grade 3‐4 thrombocytopenia observed in 4 patients (7%). CONCLUSIONS The RC and RCC regimens were highly effective and well tolerated modalities of treatment in heavily pretreated patients with indolent lymphoproliferative disorders. Cancer 2006. © 2006 American Cancer Society.