Rituximab Plus Purine Nucleoside Analogs in the Treatment of Indolent Lymphoid Malignancies

Abstract

The chimeric anti-CD20 monoclonal antibody rituximab has emerged as an effective single agent for the treatment of patients with CD20-positive indolent lymphoid malignancies (ILM). The purine nucleoside analogs (PNAs) fludarabine, cladribine, and pentostatin are also active agents in ILM and their interactions with rituximab may have important practical value. In vitrostudies have shown synergistic or additive interactions between rituximab and PNAs. The results of recent clinical studies seem to confirm these preclinical observations. Several studies suggest that adding rituximab to fludarabine, cladribine, or pentostatin in the treatment of refractory/relapsed or treatment-naive patients with chronic lymphocytic leukemia, follicular lymphoma, and other low-grade non-Hodgkin lymphomas may produce an increase in overall and complete response rates and prolong progression-free survival. Taking into account the observation that the combination of PNAs with cyclophosphamide may be more effective than PNAs alone, the combined use of rituximab with cladribine, fludarabine, or pentostatin and cyclophosphamide, or even mitoxantrone, may be even more effective than rituximab or rituximab combined with PNAs. However, the importance of such combined therapies requires further study, especially in terms of progression-free survival, overall survival, and late complications such as opportunistic infections and secondary malignancies.