Department of Hematology, Myeloma & Lymphoma Center, Shanghai Changzheng Hospital, Shanghai, China.
Department of Hematology, Henan Province Hospital of Traditional Chinese Medicine, Institute of Hematology, Henan University of Traditional Chinese Medicine, Zhengzhou, China.
Clin Cancer Res. 2024 Sep 3;30(17):3747-3756. doi: 10.1158/1078-0432.CCR-24-0414.
This study aimed to report the 5-year clinical outcomes of anti-B-cell maturation antigen chimeric antigen receptor (CAR) T-cell (HDS269B) therapy in patients with relapsed/refractory multiple myeloma (RRMM), including those with poor performance status [Eastern Cooperative Oncology Group (ECOG) scores 3 to 4], and to identify factors influencing long-term outcomes.
Forty-nine patients with RRMM enrolled from 2016 to 2020 received HDS269B (9 × 106 cells/kg) after receiving a conditioning chemotherapy consisting of cyclophosphamide and fludarabine. The overall response, long-term outcomes, and safety were assessed, as were their associations with clinical and disease characteristics.
With a median follow-up of 59.0 months, the overall response rate was 77.55%. The median progression-free survival (PFS) and overall survival (OS) were 9.5 months [95% confidence interval (CI), 5.01-13.99] and 20.0 months (95% CI, 11.26-28.74), respectively. The 5-year PFS and OS rates were 21.3% (95% CI, 12.3%-36.7%) and 34.1% (95% CI, 22.7%-51.3%), respectively. Patients with ECOG 0 to 2 had marked longer survival, with a median PFS of 11.0 months and a median OS of 41.8 months. Early minimal residual disease negativity, higher and persistent CAR T-cell expansion, and the absence of extramedullary disease were associated with better survival outcomes. No new CAR T-cell therapy-associated toxicities were observed. Importantly, ECOG scores 0 to 2, prior therapy lines <4, and CAR T-cell persistence at ≥6 months were independently associated with longer OS.
HDS269B is effective and safe, especially for patients with ECOG scores 0 to 2. Early CAR T-cell intervention may improve prognosis in patients with RRMM.
本研究旨在报告抗 B 细胞成熟抗原嵌合抗原受体（CAR）T 细胞（HDS269B）治疗复发/难治性多发性骨髓瘤（RRMM）患者的 5 年临床结果，包括体能状态较差（东部肿瘤协作组 [ECOG] 评分 3 至 4 分）的患者，并确定影响长期结果的因素。
2016 年至 2020 年期间，共纳入 49 例 RRMM 患者，在接受环磷酰胺和氟达拉滨联合预处理化疗后，给予 HDS269B（9×106 个细胞/kg）治疗。评估了总缓解率、长期结果和安全性，并分析了其与临床和疾病特征的关系。
中位随访时间为 59.0 个月，总缓解率为 77.55%。中位无进展生存期（PFS）和总生存期（OS）分别为 9.5 个月（95%置信区间 [CI]，5.01-13.99）和 20.0 个月（95%CI，11.26-28.74）。5 年 PFS 和 OS 率分别为 21.3%（95%CI，12.3%-36.7%）和 34.1%（95%CI，22.7%-51.3%）。ECOG 0 至 2 分的患者生存时间明显更长，中位 PFS 为 11.0 个月，中位 OS 为 41.8 个月。早期微小残留病灶阴性、较高和持续的 CAR T 细胞扩增以及无髓外疾病与更好的生存结果相关。未观察到新的 CAR T 细胞治疗相关毒性。重要的是，ECOG 评分 0 至 2、治疗线数<4 和 CAR T 细胞持续时间≥6 个月与 OS 延长独立相关。
HDS269B 是一种有效且安全的治疗方法，尤其适用于 ECOG 评分 0 至 2 的患者。早期 CAR T 细胞干预可能改善 RRMM 患者的预后。
