Department of Bone Marrow Transplantation, Hebei Yanda Lu Daopei Hospital, Langfang, China.
Department of Hematology and Immunology, Hebei Yanda Lu Daopei Hospital, Langfang, China.
Front Immunol. 2021 May 7;12:605766. doi: 10.3389/fimmu.2021.605766. eCollection 2021.
Patients often undergo consolidation allogeneic hematopoietic stem cell transplantation (allo-HSCT) to maintain long-term remission following chimeric antigen receptor (CAR) T-cell therapy. Comparisons of safety and efficacy of allo-HSCT following complete remission (CR) achieved by CAR-T therapy by chemotherapy for B-cell acute lymphoblastic leukemia (B-ALL) has not been reported. We performed a parallel comparison of transplant outcomes in 105 consecutive B-ALL patients who received allo-HSCT after achieving CR with CAR-T therapy (n=27) or with chemotherapy (n=78). The CAR-T-allo-HSCT group had more patients in second CR compared to the chemotherapy-allo-HSCT group (78% 37%; p<0.01) and more with complex cytogenetics (44% 6%; p<0.001) but the proportion of patients with pre-transplant minimal residual disease (MRD) was similar. The median follow-up time was 49 months (range: 25-54 months). The CAR-T cohort had a higher incidence of Grade II-IV acute graft--host disease (aGVHD 48.1% [95% CI: 46.1-50.1%] 25.6% [95%CI: 25.2-26.0%]; p=0.016). The incidence of Grade III-IV aGVHD was similar in both groups (11.1% 11.5%, p=0.945). The overall incidence of chronic GVHD in the CAR-T group was higher compared to the chemotherapy group (73.3% [95%CI: 71.3-75.3%] 55.0% [95%CI: 54.2-55.8%], p=0.107), but the rate of extensive chronic GVHD was similar (11.1% 11.9%, p=0.964). Efficacy measures 4 years following transplant were all similar in the CAR-T the chemotherapy groups: cumulative incidences of relapse (CIR; 11.1% vs.12.8%; p=0.84), cumulative incidences of non-relapse mortality (NRM; 18.7% 23.1%; p=0.641) leukemia-free survival (LFS; 70.2% 64.1%; p=0.63) and overall survival (OS; 70.2% 65.4%; p=0.681). We found that pre-transplant MRD-negative CR predicted a lower CIR and a higher LFS compared with MRD-positive CR. In conclusion, our data indicate that, in B-ALL patients, similar clinical safety outcomes could be achieved with either CD19 CAR T-cell therapy followed by allo-HSCT or chemotherapy followed by allo-HSCT. Despite the inclusion of more patients with advanced diseases in the CAR-T group, the 4-year LFS and OS achieved with CAR T-cells followed by allo-HSCT were as remarkable as those achieved with chemotherapy followed by allo-HSCT. Further confirmation of these results requires larger, randomized clinical trials.
患者在接受嵌合抗原受体 (CAR) T 细胞治疗后常进行巩固性同种异体造血干细胞移植 (allo-HSCT) 以维持长期缓解。对于接受 CAR-T 治疗后达到完全缓解 (CR) 的患者，allo-HSCT 的安全性和有效性与化疗相比尚无报道。我们对 105 例连续接受 CAR-T 治疗后达到 CR 的 B 细胞急性淋巴细胞白血病 (B-ALL) 患者（n=27）或接受化疗后达到 CR 的患者（n=78）进行了 allo-HSCT 移植结果的平行比较。与化疗allo-HSCT 组相比，CAR-T-allo-HSCT 组有更多的患者处于第二次 CR（78%比 37%；p<0.01）和更多的患者具有复杂的细胞遗传学（44%比 6%；p<0.001），但移植前微小残留病（MRD）的比例相似。中位随访时间为 49 个月（范围：25-54 个月）。CAR-T 组急性移植物抗宿主病 (aGVHD) 的发生率更高，为 2 级至 4 级（48.1%[95%CI: 46.1-50.1%]比 25.6%[95%CI: 25.2-26.0%]；p=0.016）。两组 3 级至 4 级 aGVHD 的发生率相似（11.1%比 11.5%，p=0.945）。CAR-T 组慢性移植物抗宿主病的总发生率高于化疗组（73.3%[95%CI: 71.3-75.3%]比 55.0%[95%CI: 54.2-55.8%]，p=0.107），但广泛慢性移植物抗宿主病的发生率相似（11.1%比 11.9%，p=0.964）。CAR-T 组和化疗组在移植后 4 年的疗效评估相似：复发累积发生率（CIR；11.1%比 12.8%；p=0.84）、非复发死亡率（NRM；18.7%比 23.1%；p=0.641）、无白血病生存率（LFS；70.2%比 64.1%；p=0.63）和总生存率（OS；70.2%比 65.4%；p=0.681）。我们发现，移植前 MRD 阴性 CR 与 MRD 阳性 CR 相比，CIR 更低，LFS 更高。总之，我们的数据表明，在 B-ALL 患者中，CD19 CAR-T 细胞治疗后进行 allo-HSCT 或化疗后进行 allo-HSCT 可获得相似的临床安全性结果。尽管 CAR-T 组纳入了更多疾病进展的患者，但 CAR-T 细胞治疗后 4 年的 LFS 和 OS 与化疗后 allo-HSCT 相当。这些结果需要更大规模的随机临床试验进一步证实。
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