A Phase II Trial of Rituximab Combined With Pegfilgrastim in Patients With Indolent B-cell Non-Hodgkin Lymphoma

The present phase II study has demonstrated that augmenting neutrophil function by the addition of pegfilgrastim can potentiate the clinical activity of rituximab in indolent B-cell non-Hodgkin lymphoma while retaining the excellent safety profile. Strategies to boost the innate immune system such as this combination warrant further study, especially in the frail, elderly population for whom therapeutic options are limited owing to poor tolerance. Background To explore the role of augmenting neutrophil function in B-cell lymphoma, we conducted a phase II study evaluating the safety and clinical efficacy of pegfilgrastim and rituximab in low-grade CD20 ⁺ B-cell non-Hodgkin lymphoma (B-NHL). Patients and Methods Twenty patients with indolent B-NHL were treated with rituximab (375 mg/m ² ) every other week for 4 doses, followed by every 2 months for 4 additional doses. Pegfilgrastim was administered subcutaneously 3 days before each dose of rituximab. Clinical activity and tolerability were assessed using standard criteria. Biologic monitoring included phenotype characteristics of the host neutrophils, changes in oxidative burst, and functional assays. Results The patient demographics included median age of 64 years, 70% were male, 70% had follicular lymphoma, and 90% had stage III-IV disease. The median number of previous therapies was 2 (range, 0-5); 90% had received previous anti-CD20 monoclonal antibody therapy. The addition of pegfilgrastim to rituximab did not increase rituximab-related toxicities. The overall response rate was 60% (12 of 20), with a complete response (CR) rate of 35% (7 of 20). The median progression-free survival (PFS) duration was 17.9 months (95% confidence interval, 9.9-27.6 months); the median overall survival was not reached. A shorter time-to-peak oxidative burst after the first dose of pegfilgrastim was associated with greater CR rates (P =.04) and longer PFS (P =.03). Conclusion The pegfilgrastim-rituximab combination was well tolerated, with favorable outcomes compared with historical controls. A shorter time-to-peak oxidative burst was associated with higher CR rates and longer PFS. Our results support further evaluation of strategies that enhance the innate immune system to improve rituximab activity in B-NHL.