Department of Hematology, Myeloma & Lymphoma Center, Changzheng Hospital, Naval Medical University, Shanghai, China.
Department of Hematology, Henan Province Hospital of Traditional Chinese Medicine (The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine), Institute of Hematology, Henan University of Traditional Chinese Medicine, Zhengzhou, China.
Am J Hematol. 2022 Jul;97(7):933-941. doi: 10.1002/ajh.26583. Epub 2022 May 5.
In this open-label, single-arm, phase I/II clinical trial, we evaluated the efficacy of anti-B cell maturation antigen (BCMA) chimeric antigen receptor (CAR)-T cell (HDS269B) therapy in 49 relapsed/refractory multiple myeloma (RRMM) patients, including 20 with Eastern Cooperative Oncology Group (ECOG) grade 3-4. After HDS269B infusion (9 × 10 CAR cells/kg), 17 patients (34.69%, 11 ECOG 0-2, 6 ECOG 3-4) developed cytokine release syndrome [grade 1-2: 14 patients (28.57%); grade 3: 3 patients (6.12%)]. The objective response rate (ORR) was 77%, with a complete response (CR) achieved in 47%. Ongoing response >12 months occurred in 15 patients, and was extended beyond 38 months in one patient. The median progression-free survival (PFS) and overall survival (OS) were 10 months (95% CI 5.3-14.7) and 29 months (95% CI 10.0-48.0), respectively. The PFS (12 months) and OS (18 months) rates were 41.64% and 62.76%, respectively. In patients with ECOG 0-2 and 3-4, ORR was 79.31% (23/29) and 75.0% (15/20) and PFS were 15 months (95% CI 5.4-24.6) and 4 months (95% CI 0-11.7), respectively. OS was not reached in ECOG 0-2 patients, but was 10.5 months (95% CI 0-22) in ECOG 3-4 patients. Single-cell sequencing indicated that treatment efficacy might be related to mTORC1 signaling. Thus, HDS269B therapy is safe and effective for RRMM patients, even those with ECOG 3-4.
在这项开放标签、单臂、I/II 期临床试验中，我们评估了抗 B 细胞成熟抗原 (BCMA) 嵌合抗原受体 (CAR)-T 细胞 (HDS269B) 疗法在 49 例复发/难治性多发性骨髓瘤 (RRMM) 患者中的疗效，包括 20 例东部合作肿瘤学组 (ECOG) 3-4 级患者。在 HDS269B 输注 (9×10 CAR 细胞/kg) 后，17 例患者 (34.69%，11 例 ECOG 0-2，6 例 ECOG 3-4) 发生细胞因子释放综合征 [1 级-2 级：14 例 (28.57%)；3 级：3 例 (6.12%)]。客观缓解率 (ORR) 为 77%，完全缓解 (CR) 率为 47%。15 例患者的持续缓解时间>12 个月，1 例患者的缓解时间超过 38 个月。中位无进展生存期 (PFS) 和总生存期 (OS) 分别为 10 个月 (95%CI 5.3-14.7) 和 29 个月 (95%CI 10.0-48.0)。ECOG 0-2 和 3-4 级患者的 PFS(12 个月)和 OS(18 个月)率分别为 41.64%和 62.76%。ORR 在 ECOG 0-2 级和 3-4 级患者中分别为 79.31% (23/29) 和 75.0% (15/20)，PFS 分别为 15 个月 (95%CI 5.4-24.6) 和 4 个月 (95%CI 0-11.7)，OS 无进展。ECOG 0-2 级患者未达到 OS，但 ECOG 3-4 级患者为 10.5 个月 (95%CI 0-22)。单细胞测序表明，治疗效果可能与 mTORC1 信号有关。因此，HDS269B 疗法对 RRMM 患者，甚至 ECOG 3-4 级患者是安全有效的。
