Objective: To investigate the safety and efficacy of allogeneic CAR-T cells in the treatment of relapsed/refractory multiple myeloma (RRMM) . Methods: CAR-T cells were prepared from peripheral blood lymphocytes of HLA mismatch healthy donors. Median age was 55 (48-60) . Allogeneic cells were derived from 3 HLA haploidentical donors and 1 HLA completely mismatch unrelated donor. Four patients with RRMM were conditioned with FC regimen followed by CAR-T cell transfusion. They were infused into CART-19 (1×10(7)/kg on day 0) and (4.0-6.8) ×10(7)/kg CART-BCMA cells as split-dose infusions (40% on day 1 and 60% on day 2) . The adverse reactions and clinical efficacy were observed during follow-up after infusion, and the amplification and duration of CAR-T cells in vivo were monitored by PCR technique. Results: CAR-T cells were successfully infused in 3 of the 4 RRMM patients according to the study plan, and the infusion in one patient was delayed by 1 day due to high fever and elevated creatinine levels on day 3. The side effects included hematological and non-hematological toxicity, grade 3 hematological toxicity in 2 patients, grade 3 CRS in 1 one, grade 1 CRES in 1 one, prolonged APTT in 3 ones, tumor lysis syndrome in 1 one, mixed chimerism detected STR and clinical GVHD manifestation in 1 one. According to the efficacy criterias of IMWG, 2 patients acquired PR, 1 MR, and 1 SD respectively. Progression-free survival was 4 (3-5) weeks and overall survival was 63 (3-81) weeks. CAR T cells were amplified 2.2 (2-14) times in the patients with a median survival time of 10 (8-36) days. Conclusions: Small sample studies suggested that GVHD may be present in the treatment of RRMM with allogeneic CAR-T cells. There were early clinical transient events after transfusion. Low amplification and short duration of CAR-T cells in vivo may be the main factors affecting the efficacy.
目的： 探讨同种异基因CAR-T细胞治疗复发/难治型多发性骨髓瘤（RRMM）的安全性和有效性。 方法： 采集HLA不全相合健康供者外周血淋巴细胞制备CAR-T细胞治疗4例RRMM患者，男1例、女3例。细胞来源3例为亲缘间HLA半相合供者，1例为HLA完全不合的无血缘供者。4例RRMM患者经FC方案（氟达拉滨+环磷酰胺）预处理后进行CAR-T细胞的回输，第0天回输CART-19细胞1×10(7)/kg、第1~2天分别回输CART-B细胞成熟抗原（BCMA）细胞4.7（4.0~6.8）×10(7)/kg的40%和60%（例4于第4天回输CART-BCMA细胞的60%）。 结果： 4例RRMM患者完成了CAR-T细胞输注后，CAR-T细胞在患者体内中位扩增2.20（1.93~14.01）倍，中位存活时间为10（8~36）d；根据IMWG疗效标准，2例达部分缓解（PR）、1例为微小缓解（MR）、1例为疾病稳定（SD）。不良反应包括血液学和非血液学不良反应，≥3级血液学不良反应2例、≥3级细胞因子释放综合征（CRS）1例、1级CAR-T治疗后急性反应期的中枢神经系统并发症（CRES）1例，3例患者出现APTT延长、1例患者出现肿瘤溶解综合征，1例检测到STR为混合嵌合状态，临床判断出现GVHD。无进展生存时间为4（3~5）周、总生存时间为63（3~81）周。 结论： 小样本研究显示同种异基因CAR-T细胞治疗RRMM可能会出现GVHD；回输后早期有临床反应，但疗效不能维持。同种异基因CAR-T细胞在体内扩增倍数低，持续时间短，可能是影响疗效持久的主要因素。.
Keywords: Chimeric antigen receptor T cell immunotherapy; Multiple myeloma; Relapsed and/or refractory.