Risk Factors Associated with Durable Progression-Free Survival in Patients with Relapsed or Refractory Multiple Myeloma Treated with Anti-BCMA CAR T-cell Therapy.
Risk Factors Associated with Durable Progression-Free Survival in Patients with Relapsed or Refractory Multiple Myeloma Treated with Anti-BCMA CAR T-cell Therapy.
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与接受抗 BCMA CAR T 细胞疗法治疗的复发性或难治性多发性骨髓瘤患者持久无进展生存相关的危险因素
DOI：
10.1158/1078-0432.ccr-21-2031
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发表时间：
2021-12-01
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目的：B细胞成熟抗原（BCMA）嵌合抗原受体（CAR）T细胞疗法在复发性/难治性（R/R）多发性骨髓瘤患者中产生高缓解率。然而，与CAR T细胞治疗后预后相关的因素尚不清楚。患者和方法：在2018年7月1日至2020年7月31日期间，61名R/R多发性骨髓瘤患者接受了抗BCMA CAR T细胞治疗（Chictr.org编号，ChiCTR 1800017404）。逐步多变量考克斯回归和竞争风险分析进行了识别不良预后相关的危险因素。结果如下：60例患者（98.4%）发生了细胞因子释放综合征（CRS），其中1 - 2级、3级和4级CRS分别为33例、23例和4例。客观缓解率（ORR）为98.3%，完全缓解率（CR）为70.3%。中位随访时间为21.1个月，1年总生存率（OS）和无进展生存率（PFS）分别为78.0%和50.2%。中位PFS为12.7个月。考克斯模型显示，PFS较差与髓外疾病[HR = 2.59，95%置信区间（95% CI）= 1.29-5.21，P = 0.008]、轻链多发性骨髓瘤（HR = 2.53，95% CI = 1.03-5.97，P = 0.035），高危细胞遗传学（HR = 2.80，95% CI = 1.27-6.14，P = 0.01）和既往接受过3种以上治疗线治疗（HR = 3.14，95% CI = 1.34-7.34，P = 0.008）。在41例CR病例中，竞争性风险分析表明，髓外疾病患者的复发倾向更高（HR = 4.51，95% CI = 1.86-10.9，P = 0.001），轻链多发性骨髓瘤（HR = 4.89，95%CI = 1.52 ~ 15.7，P = 0.008）或高危细胞遗传学（HR = 5.09，95%CI = 1.63-15.9，P = 0.005）。结论：抗BCMA CAR T细胞治疗R/R多发性骨髓瘤安全有效。对于有高危因素的患者，需要改善以延长缓解和更具体的个体化治疗。
Purpose: B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy results in high remission rates in patients with relapsed/refractory (R/R) multiple myeloma. However, the factors associated with prognosis following CAR T-cell therapy are unknown. Patients and Methods: Between July 1, 2018 and July 31, 2020, 61 patients with R/R multiple myeloma received anti-BCMA CAR T-cell therapy (Chictr.org number, ChiCTR1800017404). Step-wise multivariate Cox regression and competing risk analyses were conducted to identify poor prognosis–associated risk factors. Results: Sixty patients (98.4%) experienced cytokine release syndrome (CRS), including 33, 23, and 4 cases of CRS grades 1 to 2, 3, and 4, respectively. The objective response rate (ORR) was 98.3%, and the complete remission (CR) rate was 70.3%. With a median follow-up period of 21.1 months, the 1-year overall survival (OS) and progression-free survival (PFS) rates were 78.0% and 50.2%, respectively. The median PFS was 12.7 months. Cox modeling revealed that poor PFS was associated with extramedullary disease [HR = 2.59, 95% confidence interval (95% CI) = 1.29–5.21, P = 0.008], light chain multiple myeloma (HR = 2.53, 95% CI = 1.03–5.97, P = 0.035), high-risk cytogenetics (HR = 2.80, 95% CI = 1.27–6.14, P = 0.01), and prior treatment with more than 3 therapeutic lines (HR = 3.14, 95% CI = 1.34–7.34, P = 0.008). Among the 41 CR cases, competing risk analyses demonstrated higher relapse predispositions in those with extramedullary disease (HR = 4.51, 95% CI = 1.86–10.9, P = 0.001), light chain multiple myeloma (HR = 4.89, 95% CI = 1.52 – 15.7, P = 0.008), or high-risk cytogenetics (HR = 5.09, 95% CI = 1.63–15.9, P = 0.005). Conclusions: Anti-BCMA CAR T-cell therapy is safe and effective for R/R multiple myeloma. For patients with high-risk factors, improvements to extend remission and more specific individualized therapies are needed.