Cartron Guillaume, Houot Roch, Al Tabaa Yassine, Le Bras Fabien, Ysebaert Loïc, Choquet Sylvain, Jardin Fabrice, Bay Jacques-Olivier, Gros François-Xavier, Morschhauser Franck, Casasnovas Olivier, Gastinne Thomas, Thieblemont Catherine, Joris Magalie, Ricard Laure, Regny Caroline, Drieu La Rochelle Laurianne, Feugier Pierre, Marcais Ambroise, Griolet Samuel, Tarte Karin, Laurent Camille, Sesques Pierre
Department of Hematology, University Hospital of Montpellier, Montpellier, France.
UMR CNRS 5535, Montpellier, France.
Nat Cancer. 2025 Apr 3. doi: 10.1038/s43018-025-00941-2.
Persons with diffuse large B cell lymphoma (DLBCL) refractory or in first progression/relapsed (R/R) after chimeric antigen receptor T (CAR-T) cell therapy exhibit dramatic outcomes. We enrolled such persons in a phase 2 single-arm, nonblinded trial ( NCT04703686 ) to evaluate the efficacy and safety of glofitamab, a CD20-CD3 T cell-engaging bispecific antibody, using a short ramp-up regimen to reach full dose within 1 week. A total of 46 participants received at least one glofitamab infusion following obinutuzumab (anti-CD20 monoclonal antibody) pretreatment. The primary endpoint was overall survival (OS). Secondary endpoints included independent-assessed best overall metabolic response rate (OMRR) and complete metabolic response rate (CMRR), progression-free survival (PFS), duration of response, safety and tolerability and health-related quality of life. After a median follow-up of 15.3 months (95% confidence interval (CI), 10.1-17.7), the primary endpoint was met, achieving a median OS of 14.7 months (90% CI, 8.8-not reached). The best OMRR was 76.1%. The best CMRR was 45.7%. The median PFS was 3.8 months (95% CI, 2.4-19.6). Despite the shortened setup dosing, no excess cytokine release syndrome or neurotoxicity events were observed (grade ≥ 3, 0% for both). In conclusion, glofitamab improved OS in participants with R/R DLBCL after CAR-T cell therapy, with a favorable safety profile.
患有弥漫性大B细胞淋巴瘤（DLBCL）且对嵌合抗原受体T（CAR-T）细胞疗法难治或处于首次进展/复发（R/R）阶段的患者表现出显著的治疗效果。我们将此类患者纳入一项2期单臂、非盲试验（NCT04703686），以评估glofitamab（一种CD20-CD3 T细胞衔接双特异性抗体）的疗效和安全性，采用短剂量递增方案在1周内达到全剂量。共有46名参与者在接受奥妥珠单抗（抗CD20单克隆抗体）预处理后接受了至少一次glofitamab输注。主要终点是总生存期（OS）。次要终点包括独立评估的最佳总体代谢缓解率（OMRR）和完全代谢缓解率（CMRR）、无进展生存期（PFS）、缓解持续时间、安全性和耐受性以及健康相关生活质量。在中位随访15.3个月（95%置信区间（CI），10.1-17.7）后，达到了主要终点，中位OS为14.7个月（90%CI，8.8-未达到）。最佳OMRR为76.1%。最佳CMRR为45.7%。中位PFS为3.8个月（95%CI，2.4-19.6）。尽管给药设置时间缩短，但未观察到过量的细胞因子释放综合征或神经毒性事件（≥3级，两者均为0%）。总之，glofitamab改善了CAR-T细胞治疗后R/R DLBCL患者的OS，且安全性良好。
