In an article published in the British Journal of Haematology, researchers reported data from a 10-year follow-up evaluation of a previous prospective phase 2 trial ( Identifier: NCT00496873) in which they demonstrated the efficacy of pentostatin combined with cyclophosphamide and rituximab in patients with advanced-stage, indolent non-Hodgkin lymphoma.

In the original study, 83 previously untreated patients with advanced-stage, indolent non-Hodgkin lymphoma were enrolled between July 2005 and July 2007. Patients received pentostatin 4 mg/m2, cyclophosphamide 600 mg/m2, and rituximab 375 mg/m2 in 21-day cycles for 6 or 9 cycles. Study outcomes were progress-free survival (PFS), overall survival (OS), and long-term toxicities.

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Follicular lymphoma (FL), small lymphocytic lymphoma (SLL), and marginal zone lymphoma (MZL) accounted for 43.4%, 38.5%, and 18.1% of diagnoses, respectively. The overall response rate across all patients was 92%, with 97% of patients with FL, 83.9% of patients with SLL, and 100% of patients with MZL achieving complete response.

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PFS at 10 years was significantly higher for patients with FL compared with patients with MZL and SLL (71% vs 67% vs 15%; P =.0014). Bone marrow involvement (P =.0173), male sex (P =.0439), and pretreatment beta-2 microglobulin levels of 2.2 mg/L or higher (P =.0017) were associated with poorer PFS.

Across all patients, 10-year OS was 64%; median OS had not yet been reached at the time of analysis. However, as with PFS, 10-year OS was significantly greater for patients with FL compared with patients with MZL and SLL (94% vs 66% vs 39%, respectively; P =.0017). Baseline beta-2 microglobulin levels of 2.2 mg/L or higher (P =.0079) and age greater than 60 years old (P =.0105) were associated with decreased OS.

There were 2 patient deaths due to acute adverse events. Grade 3 or 4 neutropenia were the most commonly reported adverse events, occurring in 13% of chemotherapy cycles. At a median of 30 months after therapy initiation, 18 patients had developed a second malignancy.

The researchers compared their findings with results from several other clinical trials and noted that treatment with pentostatin, cyclophosphamide, and rituximab yielded similar rates of 5-year and 10-year OS, adverse events, and secondary malignancies compared with other combination therapies. They concluded, “this 10-year follow-up study confirms that pentostatin, cyclophosphamide, and rituximab is an effective, robust, and tolerable treatment regimen for patients with indolent B-cell lymphomas.”

Disclosures: Multiple authors have declared affiliations with the pharmaceutical industry. Please refer to the original study for a full list of disclosures.


1.     Khashab T, Hagemeister F, Romaguera JE, et al. Long-term overall- and progression-free survival after pentostatin, cyclophosphamide and rituximab therapy for indolent non-Hodgkin lymphoma [published online February 28, 2019]. Br J Haematol. doi: 10.1111/bjh.15814