CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Sequencing T-cell redirection therapies leads to deep and durable responses in patients with relapsed/refractory myeloma.
Sequencing T-cell redirection therapies leads to deep and durable responses in patients with relapsed/refractory myeloma.
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采用嵌合抗原受体(CAR)T细胞和双特异性抗体(BiAb)的T细胞重定向治疗,在重度经治的复发/难治性多发性骨髓瘤(RRMM)患者中显示出良好疗效,已有两种CAR-T 细胞产品获批,且多项BiAb临床试验正在开展。为制定挽救治疗的序贯策略,亟需了解BiAb治疗后复发患者的结局。研究人员确定了在西奈山医院BiAb试验后发生疾病进展的58例患者,采用Kaplan-Meier法估算首次挽救治疗的无进展生存期(PFS1)、第二次挽救治疗的无进展生存期(PFS2)和总生存期(OS)。患者中位年龄为67岁,78%具有高危细胞遗传学特征;既往治疗中位数为6线,89%对三类药物均耐药,44%对五种药物均耐药。BiAb试验结束后,患者中位随访30.5个月,中位接受2种额外挽救治疗(范围1–9种)。最常见的首次挽救治疗是T细胞重定向治疗,共19例(10例使用BiAb、9例使用CAR-T);另有10例在第二次挽救治疗中接受T细胞重定向。将T细胞重定向作为首次或第二次挽救治疗具有可行性,中位PFS1为28.9个月,中位PFS2为30.9个月,2年OS率为62%。不同T细胞重定向疗法可序贯使用,并可能使RRMM患者在BiAb治疗后复发时仍获得深度且持久的应答。
T-cell redirection therapy using chimeric antigen receptor (CAR) T cells and bispecific antibodies (BiAbs) has shown promising efficacy in heavily pretreated patients with relapsed/refractory multiple myeloma (RRMM), leading to the approval of 2 CAR T-cell products and numerous BiAb trials. Data on the outcomes after relapse following BiAbs are urgently required to develop strategies for sequencing salvage therapies.
We identified 58 patients progressing after a BiAb trial at Mount Sinai Hospital. Progression-free survival (PFS) to the first salvage (PFS1), second salvage therapy (PFS2), and overall survival (OS) were estimated using the Kaplan-Meier method. The median age of the patients was 67 years, and 78% had high-risk cytogenetics. They had a median of 6 prior therapy lines, 89% were triple-class refractory, and 44% were penta-drug refractory. After the BiAb trial, patients were followed for a median of 30.
5 months and received a median of 2 additional salvage therapies (range, 1-9). The most common first salvage was T-cell redirection in 19 patients (10 BiAb and 9 CAR T cells). Ten patients underwent T-cell redirection as a second salvage treatment.
T-cell redirection therapy as first or second salvage was feasible and associated with a median PFS1 of 28. 9 months, PFS2 of 30. 9 months, and an OS of 62% at 2 years. The sequential use of different T-cell redirection therapies is possible and may lead to deep and durable responses following the relapse after BiAb therapy in RRMM.
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