Pentostatin, Cyclophosphamide, Rituximab, and Mitoxantrone (PCRM): A New Highly Active Regimen for Patients with Chronic Lymphocytic Leukemia (CLL) Previously Treated with PCR or FCR.

Combination therapy with purine analogs, alkylators, and/or monoclonal antibodies has markedly improved the quality of responses in patients with chronic lymphocytic leukemia (CLL). Most regimens have utilized fludarabine as the purine analog but the severe myelosuppression and immunosuppression of these combinations require careful attention to dosing and schedule to minimize these toxic complications. Of the purine analogs active in CLL, pentostatin is the least myelosuppressive. Previously, we reported that combination pentostatin, cyclophosphamide, and rituximab was very active and acceptably safe to administer to patients with CLL and in the salvage setting this regimen appeared to have less myelosuppression and less frequent infectious complications than comparable fludarabine-based combinations. The current study combines pentostatin 4mg/m², cyclophosphamide 600mg/m², rituximab 375mg/m² (omitted from cycle 1) and mitoxantrone (dose escalated in a phase 1 portion starting at 6mg/m², 8mg/m², and 10mg/m²) all administered on day 1 of 28-day cycles for a total of 6 treatments. Supportive measures included prophylactic administration of pegfilgrastim, sulfamethoxazole/trimethoprim, acyclovir, and antiemetics. Renal function was closely monitored and all patients received at least 1.5 liters of intravenous hydration with the administration of chemotherapy. Twenty-one patients (median age 62, range 44–74) with CLL (17 patients) or other low grade B cell neoplasms (4 patients) have been enrolled. There were 16 men and 5 women. Of the CLL patients all had either high risk disease (71%) or “active” intermediate (29%) risk disease and their median pretreatment WBC count was 74,000/μl, HGB 9.9 g/dl, and PLT 144,000/μl. The median β-2 microglobulin was 3.3 mg/l. The median number of prior treatment regimens was two (range 1–6). Most of the CLL patients (65%) had previously been treated with chemoimmunotherapy utilizing PCR or FCR. Response data is currently available for 16/17 of the CLL patients. In this group there were 15 responses (94%), including 4 CRs (25%) and 11 PRs (69%). Prior therapy with PCR or FCR did not adversely affect the frequency of response with 91% of these patients responding (CR in 19% and PRs in 73%). These preliminary results indicate that PCRM therapy is very active and well tolerated even in patients who have previously received FCR or PCR.