在中国开展的一项 1 期、单臂、开放标签、多中心研究（LEGEND-2）中，评估 LCAR-B38M 治疗复发/难治性多发性骨髓瘤的 4 年随访结果。
Four-year follow-up of LCAR-B38M in relapsed or refractory multiple myeloma: a phase 1, single-arm, open-label, multicenter study in China (LEGEND-2).
机构信息
Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 West 5th Road, Xi'an, 710004, China.
Department of Hematology, Jiangsu Province Hospital, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
出版信息
J Hematol Oncol. 2022 Jul 6;15(1):86. doi: 10.1186/s13045-022-01301-8.
BACKGROUND
LCAR-B38M is a chimeric antigen receptor T cell product with two binding domains targeting B cell maturation antigen. Our previous reports showed a remarkable efficacy of LCAR-B38M in patients with relapsed/refractory multiple myeloma (RRMM) at a median follow-up of 2 years. Here, we report long-term safety and efficacy data from a median follow-up of 4 years.
METHODS
LEGEND-2 was a phase 1, single-arm, open-label study conducted in four registered sites in China. Seventy-four participants with RRMM received LCAR-B38M treatment. Lymphodepletion was performed using cyclophosphamide or cyclophosphamide plus fludarabine. LCAR-B38M, at a median dose of 0.513 × 10 cells/kg, was intravenously administered either in three split infusions or in a single infusion. The primary objective was the safety of LCAR-B38M, and the secondary objective was efficacy.
RESULTS
As of May 25, 2021, the median follow-up was 47.8 months. All patients experienced ≥ 1 adverse events (AEs). Grade ≥ 3 AEs were observed in 45/74 (60.8%) patients. Cytokine release syndrome (CRS) occurred in 68/74 (91.9%) cases; 7 (9.5%) had grade ≥ 3 CRS. One patient experienced grade 1 central nervous system toxicity. The overall response rate was 87.8%. Fifty-four out of 74 (73.0%) patients achieved complete response. The median progression-free survival was 18.0 months, and the median overall survival for all patients was not reached. The median duration of response was 23.3 months. Four patients experienced viral infection more than 6 months post-infusion, and four patients developed second primary non-hematological malignancies at a median time of 11.5 months post-CAR-T cell transfer.
CONCLUSIONS
The 4-year follow-up data of LCAR-B38M therapy demonstrated a favorable long-term safety profile and a durable response in patients with RRMM. Trial registration Clinicaltrials.gov NCT03090659 (retrospectively registered on March 27, 2017); ChiCTR-ONH-17012285.
背景
LCAR-B38M 是一种嵌合抗原受体 T 细胞产品，具有两个针对 B 细胞成熟抗原的结合域。我们之前的报告显示，在中位随访 2 年时，LCAR-B38M 在复发/难治性多发性骨髓瘤（RRMM）患者中具有显著疗效。在此，我们报告中位随访 4 年的长期安全性和疗效数据。
方法
LEGEND-2 是一项在中国四个注册地点进行的 1 期、单臂、开放标签研究。74 名 RRMM 患者接受了 LCAR-B38M 治疗。采用环磷酰胺或环磷酰胺加氟达拉滨进行淋巴细胞耗竭。LCAR-B38M 以 0.513×10 个细胞/kg 的中位数剂量，静脉输注，分为三次或一次输注。主要目的是 LCAR-B38M 的安全性，次要目的是疗效。
结果
截至 2021 年 5 月 25 日，中位随访时间为 47.8 个月。所有患者均经历了≥1 次不良事件（AE）。45/74（60.8%）名患者发生了≥3 级 AE。68/74（91.9%）例发生细胞因子释放综合征（CRS）；7（9.5%）例为≥3 级 CRS。1 例患者发生 1 级中枢神经系统毒性。总缓解率为 87.8%。74 例患者中有 54 例（73.0%）达到完全缓解。中位无进展生存期为 18.0 个月，所有患者的中位总生存期尚未达到。中位缓解持续时间为 23.3 个月。4 例患者在输注后 6 个月以上发生病毒感染，4 例患者在 CAR-T 细胞转移后 11.5 个月中位时间发生第二原发性非血液系统恶性肿瘤。
结论
LCAR-B38M 治疗的 4 年随访数据显示，RRMM 患者具有良好的长期安全性和持久的缓解。试验注册Clinicaltrials.gov NCT03090659（于 2017 年 3 月 27 日回顾性注册）；ChiCTR-ONH-17012285。
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