Phase II Study of Bendamustine and Ofatumumab in Elderly Patients with Newly Diagnosed Diffuse Large B‐Cell Lymphoma Who Are Poor Candidates for R‐CHOP Chemotherapy

• Published in: The oncologist (Dayton, Ohio) Ohio), 2019-08, Vol.24 (8), p.1035-e623
• Main Authors: Flinn, Ian W., Erter, Jack, Daniel, Davey B., Mace, Joseph R., Berdeja, Jesus G.
• Format: Article
• Language: English
• Subjects: Clinical Trial Results
• ISSN: 1083-7159; 1549-490X
• DOI: 10.1634/theoncologist.2019-0286

Lessons Learned The combination of ofatumumab and bendamustine in elderly patients with diffuse large B‐cell lymphoma demonstrated modest efficacy compared with standard of care. The poor response may have been due to patient age and the high rate of treatment discontinuation. Background This phase II trial evaluated the efficacy of bendamustine and ofatumumab in elderly patients with newly diagnosed diffuse large B‐cell lymphoma (DLBCL) who were not candidates for rituximab cyclophosphamide, doxorubicin, vincristine, and prednisone (R‐CHOP). Methods Patients received IV 90 mg/m2 bendamustine on days 1 and 2 of cycles 1 through 6 and IV 1,000 mg ofatumumab on days 1 and 8 of cycle 1 and on day 1 of cycles 2 through 6. Both drugs were administered at the U.S. Food and Drug Administration‐approved dose for combination therapy. All patients received premedications before each infusion of ofatumumab and hematopoietic growth factors. Treatment was administered in 21‐day cycles, with restaging after cycle 3 and cycle 6. The primary endpoint was complete response rate (CRR). Results Twelve of 21 enrolled patients completed treatment; median age was 83 years. The most common reasons for treatment discontinuation were disease progression (three patients), intercurrent illness (two patients), and death (one patient due to drug‐related sepsis and bowel necrosis and one patient due to unknown cause). Thrombocytopenia (14%), neutropenia (10%), diarrhea (10%), vomiting (10%), and dehydration (10%) were the most common grade ≥3 treatment‐related adverse events. The overall response rate was 90.5% and the CRR was 33.3%. Median progression‐free survival (PFS) and overall survival (OS) were 8.6 and 12.0 months, respectively. Conclusion The combination of ofatumumab and bendamustine is feasible in elderly patients with DLBCL. 经验总结 • 在老年弥漫大 B 细胞淋巴瘤患者中，苯达莫司汀联合奥法单抗与标准治疗相比疗效有限。 • 有效率低的原因可能是患者年龄与治疗终止率高的影响。 摘要 背景。本项 II 期试验评估了苯达莫司汀联合奥法单抗在初诊老年弥漫大 B 细胞淋巴瘤 (DLBCL) 而不适合利妥昔单抗、环磷酰胺、阿霉素、长春新碱和泼尼松 (R‐CHOP) 化疗患者中的疗效。 方法。患者在第一疗程至第六疗程的第 1 天和第 2 天接受静脉注射 90 mg/m2 苯达莫司汀，第一疗程的第 1 天和第 8 天以及第二疗程至第六疗程的第 1 天静脉注射 1 000 mg 奥法单抗。这两种药物的联合使用剂量符合美国食品和药物管理局批准。所有患者在每次输注奥法单抗和造血生长因子前均接受了药物前治疗。治疗疗程为 21 天，第 3 和第 6 个疗程后再分期。主要终点为完全缓解率 (CRR)。 结果。21 名参与患者中有 12 名完成治疗；中位年龄为 83 岁。停止治疗最常见的原因为疾病进展(3 例)、并发疾病(2 例)和死亡(1 例死于药物相关败血症和肠坏死，1 例原因不明)。3 级及以上治疗相关不良事件主要为血小板减少 (14%)、中性粒细胞减少 (10%)、腹泻 (10%)、呕吐 (10%) 和脱水 (10%)。总缓解率为 90.5%，CRR为 33.3%。中位无进展生存期 (PFS) 和总生存期 (OS) 分别为 8.6 个月和 12.0 个月。 结论。奥法单抗联合苯达莫司汀在老年 DLBCL 的治疗中具有可行性。