肿瘤细胞治疗研究
英文原题：Allogeneic Hematopoietic Cell Transplantation after Chimeric Antigen Receptor T Cell Therapy in Large B Cell Lymphoma.
Allogeneic Hematopoietic Cell Transplantation after Chimeric Antigen Receptor T Cell Therapy in Large B Cell Lymphoma.
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抗CD19CAR-T 细胞疗法已改变了复发/难治性大B细胞淋巴瘤（LBCL）患者的治疗格局。然而，约60%的CAR-T 接受者最终会出现疾病复发或进展。CAR-T 治疗失败后的挽救治疗疗效有限，且缓解持续时间短。
本研究旨在评估异基因造血细胞移植（allo-HCT）在LBCL患者接受CAR-T 治疗后的作用。这是一项多中心观察性研究，报告了39例接受抗CD19 CAR-T 治疗后进行allo-HCT的成人LBCL患者的结局。患者中位年龄为47岁（范围，20至68岁）。HLA相合同胞、HLA相合无关供者及替代供者分别用于36%、36%和28%的移植。预处理方案主要为低强度或中强度。allo-HCT时的疾病状态为完全缓解占41%，部分缓解占38%，疾病进展占21%。allo-HCT在CAR-T 治疗后中位127天（范围，82至206天）进行。观察到肝脏毒性发生率高（28%），包括肝窦阻塞综合征（15.4%；95%置信区间[CI]，6.2%至28.5%）。II-IV级和III-IV级急性移植物抗宿主病（GVHD）的1年累积发生率分别为38.5%（95% CI，23.2%至53.6%）和15.4%（95% CI，6.1%至28.5%）。中重度慢性GVHD的2年累积发生率为11.1%（95% CI，3.3%至24.3%）。
总体而言，2年非复发死亡率和复发/进展发生率分别为26%（95% CI，13%至41%）和43%（95% CI，27%至59%）。中位随访32个月，2年OS和PFS分别为45%（95% CI，31%至66%）和31%（95% CI，19%至50%）。在多变量分析中，HCT前乳酸脱氢酶水平升高和转化性淋巴瘤分别预测OS和PFS。
我们的数据表明，抗CD19 CAR-T 治疗失败后进行allo-HCT是可行的，具有相对较好的疗效，但毒性率可能较高。
Anti-CD19 chimeric antigen receptor T cell (CAR-T) therapy has transformed the care of patients with relapsed/refractory large B cell lymphoma (LBCL).
However, approximately 60% of CAR-T recipients ultimately will experience disease recurrence or progression. Salvage therapies after CAR-T treatment failures are of limited efficacy and have a short duration of response. The objective of the present study was to evaluate the role of allogeneic hematopoietic cell transplantation (allo-HCT) after CAR-T therapy in LBCL patients. This was a multicenter observational study reporting the outcome of 39 adult LBCL patients who underwent allo-HCT following anti-CD19 CAR-T therapy. The median patient age was 47 years (range, 20 to 68 years). HLA-matched sibling, HLA-matched unrelated, and alternative donors were used in 36%, 36%, and 28% of transplantations, respectively.
Conditioning regimens were primarily of low or intermediate intensity. Disease status at allo-HCT was complete response in 41%, partial response in 38%, and progressive disease in 21%. Allo-HCT was performed at a median of 127 days (range, 82 to 206 days) after CAR-T therapy. A high incidence of hepatic toxicity (28%), including sinusoidal obstruction syndrome (15.
4%; 95% confidence interval; [CI], 6. 2% to 28. 5%), was observed. The 1-year cumulative incidence of grade II-IV and grade III-IV acute graft-versus-host disease (GVHD) was 38. 5% (95% CI, 23. 2% to 53. 6%) and 15. 4% (95% CI, 6. 1% to 28. 5%), respectively. The 2-year cumulative incidence of moderate-severe chronic GVHD was 11. 1% (95% CI, 3. 3% to 24. 3%).
Overall, 2-year nonrelapse mortality and relapse/progression incidence were 26% (95% CI, 13% to 41%) and 43% (95% CI, 27% to 59%), respectively. With a median follow-up of 32 months, the 2-year overall survival (OS) and progression-free survival (PFS) were 45% (95% CI, 31% to 66%) and 31% (95% CI, 19% to 50%), respectively. In multivariable analyses, pre-HCT elevated lactate dehydrogenase level and transformed lymphoma were predictive of OS and PFS, respectively.
Our data suggest that allo-HCT after anti-CD19 CAR-T treatment failure is feasible with a relatively promising efficacy but possibly high toxicity rate.
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