An open‐label pilot study of pentostatin, mitoxantrone, and rituximab in patients with previously untreated, Stage III or IV, low‐grade non‐Hodgkin lymphoma

BACKGROUND In a previous study, the authors demonstrated that the combination of pentostatin (P) and rituximab (R) was well tolerated and was active in patients with low‐grade non‐Hodgkin lymphoma (NHL). In the current study, mitoxantrone (M) was added to P + R to evaluate the toxicity and efficacy of this three‐drug combination (PMR). METHODS Twenty‐four previously untreated patients with histologically proven, Stage III or IV, low‐grade NHL were registered between April and September, 2002. Patients received P (4 mg/m2), M (10 mg/m2), and R (375 mg/m2) every 28 days (M on Day 1; P and R on Days 1 and 8; in Cycle 1, R was given on Day 8 only). Eighty‐three percent of patients had Stage IV disease, the median patient age was 62 years (range, 4–81 years), and the performance status was 0–2. RESULTS Responses included 9 patients who achieved complete remission (CR) (38%), 3 patients with unconfirmed CR (CRu) (12%), 8 patients who achieved partial remission (33%), and 4 patients who achieved stable disease (17%); the overall response rate (CR + CRu + PR) was 83%. PMR appeared to result in comparable activity in all histologies. The median response duration was 10.0 months (range, 3.5–15.1 months). Patients received a median of 5 cycles (range, 1–10 cycles). Eighteen patients (75%) required dose reduction or delay due to toxicity, mainly neutropenia (the administration of growth factors was not permitted). Three patients died (two patients died of disease progression, and one patient died from unrelated cardiopulmonary arrest). Grade ≥ 3 drug‐related toxicities included neutropenia (67%), leukopenia and febrile neutropenia (17% each), and sepsis (8%), and 38% of neutropenic episodes occurred in Cycles 1 and 2. CONCLUSIONS In this study, PMR was active and well‐tolerated in patients with low‐grade NHL, and the combination is deserving of further study. Cancer 2005. © 2005 American Cancer Society. In this first reported use of pentostatin, rituximab, and mitoxantrone as a combined regimen for the treatment of patients with previously untreated, low‐grade non‐Hodgkin lymphoma, the efficacy produced by the combination (83%) was better than each of the drugs as single‐agents, and the toxicities were moderate but manageable.