Corona Magdalena, Ip Andrew, Brown Samantha, Luna Alejandro, Khatib Hazim, Flynn Jessica R, Devlin Sean M, Landego Ivan, Cassanello Giulio, Rejeski Kai, Zuckerman Tsila, Dahi Parastoo B, Scordo Michael, Lin Richard J, Kabat Maciej, Luttwak Efrat, Pavkovic Emma, Palomba M Lia, Park Jae, Salles Gilles, Schoder Heiko, Leithner Doris, Leslie Lori A, Perales Miguel-Angel, Beyar-Katz Ofrat, Shah Gunjan L, Shouval Roni
Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Lymphoma Service, Hackensack Meridian Health, New Jersey, NJ, USA.
Bone Marrow Transplant. 2025 Apr;60(4):491-498. doi: 10.1038/s41409-025-02519-z. Epub 2025 Feb 1.
CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy has recently been approved as second-line treatment for relapsed/refractory large B-cell lymphoma (LBCL). This study compares patterns of disease relapse and progression across patients receiving CAR-T as second-line (early administration) versus third or subsequent lines (late administration). We analyzed 354 patients treated with Axicabtagene ciloleucel (71%) and Lisocabtagene maraleucel (29%); 80 (23%) received early administration, and 274 (77%) late administration. One-year overall survival was higher in the early group (82% [95% CI 72-93] vs. 71% [95% CI 66-77], p = 0.048). However, the survival benefit was not sustained in multivariable Cox regression modeling and propensity score matching. One-year cumulative incidences of relapse were similar (37% [95% CI 24-50] vs. 43% [95% CI 37-49], p = 0.2), as were 1-year progression-free survival probabilities (62% [95% CI 50-76] vs. 50% [95% CI 44-57], p = 0.14). The early group exhibited a favorable toxicity profile, with lower rate of grade ≥2 cytokine release syndrome (26% vs. 39%, p = 0.031) and reduced cumulative incidence of severe neutropenia (41% [95% CI 30-52] vs. 55% [95% CI 49-60], p = 0.027). Our results indicate favorable outcomes with CAR-T irrespective of treatment line. The equivalence in disease control suggests that CAR-T resistance mechanisms persist in LBCL failing first-line therapy.
CD19导向的嵌合抗原受体T细胞（CAR-T）疗法最近已被批准作为复发/难治性大B细胞淋巴瘤（LBCL）的二线治疗方法。本研究比较了接受CAR-T二线治疗（早期给药）与三线或后续治疗（晚期给药）患者的疾病复发和进展模式。我们分析了354例接受阿基仑赛（71%）和瑞基奥仑赛（29%）治疗的患者；80例（23%）接受早期给药，274例（77%）接受晚期给药。早期给药组的1年总生存率更高（82%[95%CI 72-93] vs. 71%[95%CI 66-77]，p = 0.048）。然而，在多变量Cox回归模型和倾向评分匹配中，生存获益并未持续。1年复发累积发生率相似（37%[95%CI 24-50] vs. 43%[95%CI 37-49]，p = 0.2），1年无进展生存概率也相似（62%[95%CI 50-76] vs. 50%[95%CI 44-57]，p = 0.14）。早期给药组的毒性特征较好，≥2级细胞因子释放综合征发生率较低（26% vs. 39%，p = 0.031），严重中性粒细胞减少的累积发生率降低（41%[95%CI 30-52] vs. 55%[95%CI 49-60]，p = 0.027）。我们的结果表明，无论治疗线数如何，CAR-T治疗都有良好的效果。疾病控制方面的等效性表明，CAR-T耐药机制在一线治疗失败的LBCL中持续存在。
