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PCR Immunochemotherapy for Previously Untreated CLL

The regimen of pentostatin, cyclophosphamide, and rituximab (PCR) yielded an overall response rate >90% in patients with previously untreated progressive CLL.

B-cell chronic lymphocytic leukemia (CLL) is the most prevalent leukemia in Western countries. The clinical course is highly variable, reflecting the heterogeneity of underlying phenotypes. Achieving more complete and durable responses, especially for older patients and those with high-risk features, remains a goal for new therapeutic approaches.

In this phase II trial, conducted at Mayo Clinic and The Ohio State University, previously untreated patients with progressive CLL were treated with six 21-day cycles of pentostatin (2 mg/m²), cyclophosphamide (600 mg/m²) and rituximab (375 mg/m²), known as the PCR regimen. All drugs were given on day 1 of each cycle, with the exception of thrice-weekly rituximab, which was given during the first week of cycle 1 only. Filgrastim was administered with each cycle, and antimicrobial prophylaxis with trimethoprim-sulfamethoxazole and acyclovir was given for 1 year. Of 64 evaluable patients, 41% achieved complete remission (CR), 22% achieved nodular partial remission (nPR; residual marrow nodules only), and 28% achieved PR, for an overall response rate of 91%. The median duration of response was significantly longer for the CR and nPR patients than for those with PR (35.6 vs. 13.1 months). Responses were comparable in older (70) and younger patients, and in patients with a high-risk cytogenetic marker (11q22.3) and those with lower-risk molecular features. PCR generally was well tolerated in both younger and older patients; overall, 34 patients exhibited grade 3 or 4 hematologic toxicity, and 25 had at least one dose held or modified during treatment. Two deaths were deemed possibly treatment related, and 2% of cycles were associated with grade 3 or worse infections.

Comment: The PCR regimen, which earlier studies showed to be active in patients with relapsed CLL, also has high activity in previously untreated patients, including those with high-risk features. Response rates, especially CR, appear lower than those reported in a large single-institution trial of fludarabine, cyclophosphamide, and rituximab (FCR; J Clin Oncol 2005; 23:4079), although PCR might be better tolerated than FCR in older patients. PCR also offers the convenience of single-day treatment after cycle 1 and a shorter overall duration of treatment (3-week, instead of 4-week, cycles). Comparative multicenter trials of PCR versus FCR or other F-based regimens will be of interest, as will correlative studies of responses among clinical, phenotypic, and molecular subsets of CLL patients.

— Michael E. Williams, MD

Published in Journal Watch Oncology and Hematology February 5, 2007

Citation(s):

Kay NE et al. Combination chemoimmunotherapy with pentostatin, cyclophosphamide, and rituximab shows significant clinical activity with low accompanying toxicity in previously untreated B chronic lymphocytic leukemia. Blood 2007 Jan 15; 109:405-11.

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