Azacitidine followed by R-GDP in transplant-ineligible relapsed/refractory diffuse large B-cell lymphoma: preliminary results from a multicenter, phase II study.

Abstract

Background: Epigenetic priming prior to chemotherapy represents a promising treatment strategy for refractory or relapsed diffuse large B-cell lymphoma (R/R DLBCL). We conducted a phase II trial to evaluate the efficacy and safety of azacitidine in combination with R-GDP (rituximab/gemcitabine/dexamethasone/cisplatin) in transplant-ineligible R/R DLBCL.

Methods: Fifteen patients were enrolled and treated with azacitidine and R-GDP regimen (NCT03719989). Azacitidine was administered intravenously at a dose of 25 mg/m²/day for 5 days. Each cycle consisted of 21 days, with patients receiving up to a maximum of six cycles. The primary endpoint was the objective response rate, and the secondary objectives were toxicity, progression-free survival (PFS), and overall survival (OS).

Results: Overall, 15 patients were enrolled in the study from March 2019 to August 2023, and the median age was 64 years (range: 41-75). The objective response rate was 66.7% with a complete response rate of 53.3%. The most common grade 3 or higher adverse events were hematologic toxicities, including neutropenia (66.7%) and thrombocytopenia (53.3%). Grade 3 or higher non-hematologic toxicities were rare, and most adverse events were transient and manageable. During a median follow-up of 15.8 months, five patients died, all from DLBCL. The median PFS was 12.6 months, while the median OS was not reached.

Conclusion: Our study suggests that azacitidine followed by R-GDP is an effective and safe strategy for transplant-ineligible patients with R/R DLBCL. This represents the first phase II study to demonstrate the potential of epigenetic priming with azacitidine to enhance chemosensitivity in this patient population.Trial registration: ClinicalTrials.gov identifier: NCT03719989.