Othman Tamer, Frankel Paul, Allen Pamela, Popplewell Leslie L, Shouse Geoffrey, Siddiqi Tanya, Danilov Alexey V, Ruel Nora, Daniels Shari, Peters Lacolle, Khoo Stella, Rosen Steven T, Sharon Elad, Villalona-Calero Miguel, Ruel Christopher, Tuscano Joseph, Herrera Alex F
Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA.
Department of Computational and Quantitative Medicine, City of Hope National Medical Center, Duarte, CA.
Haematologica. 2025 Jan 1;110(1):142-152. doi: 10.3324/haematol.2024.285185.
Patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) transformed from indolent B-cell lymphomas, including Richter transformation, have a poor prognosis. PD-1/PD-L1 antibodies produce modest objective and complete response rates in B-cell non-Hodgkin lymphoma as monotherapy but may synergize with immunogenic chemotherapies such as gemcitabine and oxaliplatin (GemOx). Thus, we evaluated the safety and efficacy of atezolizumab plus rituximab and GemOx (R-GemOx+Atezo) in R/R transformed DLBCL, including Richter transformation. We conducted a phase I trial including patients with transformed DLBCL after ≥1 prior therapy. Patients received up to four cycles of R-GemOx+Atezo. Patients in complete remission could then proceed to R-Atezo maintenance until progression. A safety lead-in with evaluation of dose-limiting toxicity was performed to confirm the recommended phase II dose; subsequently the treatment was administered to two expansion cohorts: one with transformed follicular lymphoma (FL) and the other with non-FL transformed DLBCL, including Richter transformation. Twenty-seven patients were enrolled. One of the six patients in the safety lead-in had a dose-limiting toxicity attributed to atezolizumab, a grade 4 Stevens-Johnson syndrome. The most common grade ≥3 events were neutropenia (18.5%), lymphopenia (18.5%), and thrombocytopenia (14.8%). The overall and complete response rates were 59% and 33%, respectively. The overall and complete response rates in transformed FL were 79% and 43%, respectively, and 38% and 23% in transformed non-FL, respectively. The median progression-free survival and overall survival of the total population were 4.2 and 7.7 months, respectively. R-GemOx+Atezo was well tolerated and demonstrated promising preliminary efficacy in patients with relapsed/refractory transformed DLBCL.
从惰性B细胞淋巴瘤转化而来的复发/难治性弥漫性大B细胞淋巴瘤（DLBCL）患者，包括里氏转化患者，预后较差。PD-1/PD-L1抗体作为单一疗法在B细胞非霍奇金淋巴瘤中产生的客观缓解率和完全缓解率适中，但可能与吉西他滨和奥沙利铂（GemOx）等免疫原性化疗药物协同作用。因此，我们评估了阿替利珠单抗联合利妥昔单抗和GemOx（R-GemOx+阿替利珠单抗）在复发/难治性转化型DLBCL（包括里氏转化）中的安全性和疗效。我们开展了一项I期试验，纳入了接受过≥1次先前治疗的转化型DLBCL患者。患者接受多达四个周期的R-GemOx+阿替利珠单抗治疗。完全缓解的患者随后可继续接受R-阿替利珠单抗维持治疗，直至疾病进展。进行了安全性导入期试验以评估剂量限制性毒性，从而确定推荐的II期剂量；随后将治疗应用于两个扩展队列：一个是转化型滤泡性淋巴瘤（FL）队列，另一个是非FL转化型DLBCL队列，包括里氏转化患者。共入组了27例患者。安全性导入期的6例患者中有1例出现了归因于阿替利珠单抗的剂量限制性毒性，为4级史蒂文斯-约翰逊综合征。最常见的≥3级事件为中性粒细胞减少（18.5%）、淋巴细胞减少（18.5%）和血小板减少（14.8%）。总缓解率和完全缓解率分别为59%和33%。转化型FL的总缓解率和完全缓解率分别为79%和43%，转化型非FL的分别为38%和23%。总人群的中位无进展生存期和总生存期分别为4.2个月和7.7个月。R-GemOx+阿替利珠单抗耐受性良好，在复发/难治性转化型DLBCL患者中显示出有前景的初步疗效。
