Originally published as JCO Early Release 10.1200/JCO.2005.04.3836 on March 6 2006

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Pentostatin, Cyclophosphamide, and Rituximab Is an Active, Well-Tolerated Regimen for Patients With Previously Treated Chronic Lymphocytic Leukemia

Nicole Lamanna, Matt Kalaycio, Peter Maslak, Joseph G. Jurcic, Mark Heaney, Renier Brentjens, Andrew D. Zelenetz, Denise Horgan, Alison Gencarelli, Katherine S. Panageas, David A. Scheinberg, Mark A. Weiss

From the Leukemia Service, Memorial Sloan-Kettering Cancer Center, New York, NY; Cleveland Clinic Foundation, Cleveland, OH.

Address reprint requests to Mark A. Weiss, MD, Leukemia Service, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021; e-mail: weissm{at}mskcc.org

PURPOSE: Purine analogs and alkylators are important agents for treating chronic lymphocytic leukemia (CLL). Early studies combining fludarabine and chlorambucil were abandoned owing to increased toxicity from overlapping myelosuppression and immunosuppression. Of the purine analogs active in CLL, pentostatin appears to be the least myelosuppressive. We previously reported that pentostatin and cyclophosphamide (PC) is active and well-tolerated in patients with relapsed or refractory CLL. Subsequently, we added rituximab, and now report on this three-drug combination.

PATIENTS AND METHODS: We treated 46 patients with either previously treated CLL (32 patients) or other low-grade B-cell neoplasms (14 patients). Patients received pentostatin 4 mg/m², cyclophosphamide 600 mg/m², and rituximab 375 mg/m² (PCR). All drugs were administered on the same day (rituximab omitted from cycle 1), and patients received six cycles at 3-week intervals. Filgrastim, sulfamethoxazole/trimethoprim, and acyclovir were administered prophylactically.

RESULTS: The median age was 62 years (range, 30 to 80 years). The median number of prior regimens was two (range, one to seven). For CLL patients, there were 24 responses (75%), including eight complete responses (25%). In fludarabine-refractory patients, 75% responded. Toxicity was acceptable, with grade 3/4 infections (including fever of unknown origin) in 28%. The regimen was well tolerated, with 72% of patients receiving the planned treatment at full dose.

CONCLUSION: PCR is safe and effective in previously treated patients with CLL. In comparison with our prior two-drug regimen, we find that rituximab did not seem to add significantly to the toxicity, but did appear to confer a survival advantage. Based on these results, we are currently studying PCR as initial therapy for patients with CLL.

Supported by grants from SuperGen, the Michael Sweig Foundation, The Beatrice Renfield Foundation, and the Lymphoma Foundation.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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