Kim Dong Hyun, Kong Jee Hyun, Hong Junshik, Byun Ja Min, Shin Dong-Yeop, Koh Youngil, Kim Inho, Park Jinny, Do Young Rok, Kim Jeong-A, Kim Won Seog, Shin Ho-Jin, Yoon Sung-Soo
Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea.
Department of Translational Medicine, Seoul National University College of Medicine, Seoul, South Korea.
Ther Adv Hematol. 2025 Jul 11;16:20406207251349361. doi: 10.1177/20406207251349361. eCollection 2025.
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.
Fifteen patients were enrolled and treated with azacitidine and R-GDP regimen (NCT03719989). Azacitidine was administered intravenously at a dose of 25 mg/m/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).
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.
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. ClinicalTrials.gov identifier: NCT03719989.
化疗前的表观遗传启动是难治性或复发性弥漫性大B细胞淋巴瘤（R/R DLBCL）的一种有前景的治疗策略。我们进行了一项II期试验，以评估阿扎胞苷联合R-GDP（利妥昔单抗/吉西他滨/地塞米松/顺铂）治疗不适合移植的R/R DLBCL的疗效和安全性。
15例患者入组并接受阿扎胞苷和R-GDP方案治疗（NCT03719989）。阿扎胞苷静脉给药，剂量为25mg/m²/天，共5天。每个周期为21天，患者最多接受6个周期。主要终点是客观缓解率，次要终点是毒性、无进展生存期（PFS）和总生存期（OS）。
总体而言，2019年3月至2023年8月共有15例患者入组本研究，中位年龄为64岁（范围：41-75岁）。客观缓解率为66.7%，完全缓解率为53.3%。最常见的3级或更高等级不良事件是血液学毒性，包括中性粒细胞减少（66.7%）和血小板减少（53.3%）。3级或更高等级的非血液学毒性罕见，大多数不良事件是短暂且可控制的。在中位随访15.8个月期间，5例患者死亡，均死于DLBCL。中位PFS为12.6个月，而中位OS未达到。
我们的研究表明，阿扎胞苷序贯R-GDP是治疗不适合移植的R/R DLBCL患者的一种有效且安全的策略。这是第一项证明阿扎胞苷进行表观遗传启动以增强该患者群体化疗敏感性潜力的II期研究。ClinicalTrials.gov标识符：NCT03719989。
