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/m(2) 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/m(2) on Day 1, 2-CdA at a dose of 0.12 mg/m(2) on Days 2 through 4, and intravenous cyclophosphamide at a dose of 250 mg/m(2) 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.