Abstract

Combination therapy with purine analogs, alkylators, and/or monoclonal antibodies represents a promising new approach in the treatment of patients with chronic lymphocytic leukemia (CLL) and other low grade B cell neoplasms. Most regimens have utilized fludarabine as the purine analog, but the severe myelosuppression and immunosuppression of these combinations requires careful attention to dosing and schedule to minimize these complications. Of the purine analogs in CLL, pentostatin appears to be least myelosuppressive. We have previously reported our experience with pentostatin and cyclophosphamide (PC regimen) in a cohort of heavily pretreated patients with CLL (

JCO
21
:
1278
,
2003
). We have since added rituximab to this active combination (PCR regimen) and have treated a second cohort of patients with CLL and other low grade B cell neoplasms. We now report on our cumulative experience of 69 patients (23 received PC and 46 received PCR) treated with pentostatin combination therapy.

The PC regimen consisted of pentostatin 4mg/m2 and cyclophosphamide 600mg/m2, given every 3 weeks for a total of 6 treatments. In the 2nd cohort of CLL patients, rituximab 375mg/m2 was added to this regimen starting with cycle 2. Supportive measures in both studies included hydration with each treatment (and monitoring of renal function) and prophylactic administration of filgrastim, sulfamethoxazole/trimethoprim, acyclovir, and antiemetics. In the first cohort of patients treated with the PC regimen, the median number of prior treatments was 3 (range 1–5) with the median age being 64 (32–77). There were responses achieved in 74% of patients with 17% complete responses seen in this heavily pretreated group. Similar (or perhaps slightly better) results were obtained with patients treated with the PCR regimen. For this cohort the median age was 62 (30–80) and the median number of prior regimens was 2 (1–7). Of the 32 patients with CLL 28 are evaluable for response: 79% responded and this includes 29% who achieved a complete response. Ten of the 14 patients with other low grade B cell diseases (SLL 8 patients, Waldenstrom’s macroglobulinemia 2 patients, follicular lymphoma 4 patients) are evaluable for response. The overall response rate for these patients was 50% (all PRs). These regimens were generally well tolerated with grade 3/4 toxicity consisting primarily of myelosuppression and its complications. We conclude that PC and PCR are highly active, well tolerated regimens even in heavily pretreated patients. We plan to conduct a multicenter study of PCR as initial therapy in patients with CLL.

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