Thiruvengadam Swetha Kambhampati, Merryman Reid, Wang Yan, Gaulin Charles, Bezerra Evandro, Voorhees Timothy, Seshadri Madhav R, Falade Ayo, Habib Alma, Ayers Amy A, Bailey Megumi, Brown Annette, Bailey Neil, Patel Krish, Andreadis Charalambos B, Kittai Adam S, Jacobson Caron, Palmer Joycelynne, Forman Stephen J, Nastoupil Loretta, Budde Lihua E
Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California, USA.
Department of Hematologic Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA.
Am J Hematol. 2025 Feb;100(2):236-248. doi: 10.1002/ajh.27548. Epub 2024 Dec 23.
Chimeric antigen receptor (CAR) T-cell therapy has revolutionized treatment of aggressive large B-cell lymphoma (aLBCL). Patients with transformed indolent non-Hodgkin lymphoma (tiNHL) were included in key CAR trials, but outcomes of CAR for this distinct, historically high-risk group are poorly understood. We conducted a multicenter retrospective study of 1182 patients with aLBCL receiving standard-of-care CAR T between 2017 and 2022, including 338 (29%) with tiNHL. Rates of grade ≥ 3 cytokine release syndrome (CRS) were similar between tiNHL and de novo cohorts (7% vs. 8%, p = 0.6), while grade ≥ 3 immune effector cell-associated neurotoxicity syndrome was lower in tiNHL (21% vs. 27%, p = 0.02). Overall response rate was similar in both cohorts (83% vs. 81%, p = 0.3), while complete response rate was higher in tiNHL (67% vs. 59%, p = 0.017). With a median follow-up of 22.3 months, the progression/relapse-free (PFS) and overall survival (OS) were similar between the tiNHL and de novo cohorts (24-month PFS 41% [95% CI: 35%-46%] vs. 38% [95% CI: 35%-42%]; 24-month OS 58% [95% CI: 52%-63%] vs. 52% [95% CI: 48%-56%], respectively). After adjusting for key risk factors, there was a trend toward a lower hazard of disease progression, relapse or death post-CAR for tiNHL patients compared to de novo aLBCL patients (HR: 0.84 [95% CI: 0.69-1.0], p = 0.07). Elevated LDH, advanced stage, prior bendamustine within 12 months of CAR, receipt of bridging therapy, CNS involvement, and ≥ 3 prior lines of therapy were each associated with inferior PFS. In conclusion, CAR T therapy is highly effective with an acceptable toxicity profile in patients with tiNHL.
嵌合抗原受体（CAR）T细胞疗法彻底改变了侵袭性大B细胞淋巴瘤（aLBCL）的治疗方式。转化型惰性非霍奇金淋巴瘤（tiNHL）患者被纳入了关键的CAR试验，但对于这个独特的、历史上高风险群体的CAR治疗结果却知之甚少。我们对2017年至2022年间接受标准护理CAR T治疗的1182例aLBCL患者进行了一项多中心回顾性研究，其中包括338例（29%）tiNHL患者。tiNHL组和初治组中≥3级细胞因子释放综合征（CRS）的发生率相似（7%对8%，p = 0.6），而tiNHL组中≥3级免疫效应细胞相关神经毒性综合征的发生率较低（21%对27%，p = 0.02）。两组的总体缓解率相似（83%对81%，p = 0.3），而tiNHL组的完全缓解率更高（67%对59%），p = 0.017）。中位随访22.3个月，tiNHL组和初治组的无进展/复发（PFS）和总生存期（OS）相似（24个月PFS分别为41% [95% CI：35%-46%]对38% [95% CI：35%-42%]；24个月OS分别为58% [95% CI：52%-63%]对52% [95% CI：48%-56%]）。在调整关键风险因素后，与初治aLBCL患者相比，tiNHL患者CAR治疗后疾病进展、复发或死亡风险有降低趋势（HR：0.84 [95% CI：0.69-1.0]，p = 0.07）。乳酸脱氢酶升高、晚期、CAR治疗前12个月内曾接受苯达莫司汀治疗、接受桥接治疗、中枢神经系统受累以及≥3线既往治疗均与较差的PFS相关。总之，CAR T疗法对tiNHL患者高效且毒性可接受。
