Pentostatin and rituximab therapy for previously untreated patients with B-cell chronic lymphocytic leukemia

BACKGROUND: The combination of pentostatin (P), cyclophosphamide (C), and rituximab (R) achieved an overall response (OR) rate >90%, with >40% complete responses (CRs) in patients with untreated chronic lymphocytic leukemia (CLL). METHODS: To evaluate whether the tolerability of this regimen could be enhanced without sacrificing efficacy, a phase 2 trial was conducted of P and R without C, using a higher P dose (4 mg/m²). Among the 33 patients enrolled, 82% were male, the median age was 65 years (9 patients were aged ≥70 years), and 64% were classified as having Rai stage III to IV disease. RESULTS: The OR rate was 76%, with 9 CRs (27%), 5 nodular partial responses, and 11 partial responses (PRs) reported. At the time of last follow-up, 29 of 33 patients were still alive at a median follow-up of 14 months (range, 1-34.8 months). Four (12%) patients experienced grade 3 or higher hematologic toxicity, and 5 (15%) experienced grade 3 or higher nonhematologic toxicity. Comparison of this trial with the previous PCR trial demonstrated that patients treated with PCR had a higher OR rate (91% vs 76%) and CR rate (41% vs 27%) compared with patients treated with PR. The median treatment-free survival for all accrued patients was notably longer in patients treated with PCR compared with PR (30 months vs 16 months). CONCLUSIONS: The findings of the current study suggest that increasing the dose of the purine nucleoside analogue does not eliminate the need for cyclophosphamide in chemoimmunotherapy for the treatment of CLL.