Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Department of Hematology, The First People's Hospital of Suqian, Suqian, China.
Front Immunol. 2021 Oct 29;12:755549. doi: 10.3389/fimmu.2021.755549. eCollection 2021.
Early response could be obtained in most patients with relapsed or refractory B cell lymphoblastic leukemia (R/R B-ALL) treated with chimeric antigen receptor T-cell (CAR-T) therapy, but relapse occurs in some patients. There is no consensus on treatment strategy post CAR-T cell therapy. In this retrospective study of humanized CD19-targeted CAR-T cell (hCART19s) therapy for R/R B-ALL, we analyzed the patients treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT) or received a second hCART19s infusion, and summarized their efficacy and safety. We retrospectively studied 28 R/R B-ALL patients treated with hCART19s in the Affiliated Hospital of Xuzhou Medical University from 2016 to 2020. After the first hCART19s infusion, 10 patients received allo-HSCT (CART+HSCT group), 7 patients received a second hCART19s infusion (CART2 group), and 11 patients did not receive HSCT or a second hCART19s infusion (CART1 group). The safety, efficacy, and long-term survival were analyzed. Of the 28 patients who received hCART19s treatment, 1 patient could not be evaluated for efficacy, and 25 (92.6%) achieved complete remission (CR) with 20 (74.7%) achieving minimal residual disease (MRD) negativity. Seven (25%) patients experienced grade 3-4 CRS, and one died from grade 5 CRS. No patient experienced ≥3 grade ICANS. The incidence of second CR is higher in the CART+HSCT group compared to the CART2 group (100% 42.9%, p0.015). The median follow-up time was 1,240 days (range: 709-1,770). Significantly longer overall survival (OS) and leukemia-free survival (LFS) were achieved in the CART+HSCT group (median OS and LFS: not reached, p0.006 and 0.001, respectively) compared to the CART2 group (median OS: 482; median LFS: 189) and the CART1 group (median OS: 236; median LFS: 35). In the CART+HSCT group, the incidence of acute graft--host disease (aGVHD) was 30% (3/10), and transplantation-related mortality was 30% (3/10). No chronic GVHD occurred. Multivariate analysis results showed that blasts ≥ 20% in the bone marrow and MRD ≥ 65.6% are independent factors for inferior OS and LFS, respectively, while receiving allo-HSCT is an independent factor associated with both longer OS and LFS. In conclusion, early allo-HSCT after CAR-T therapy can achieve long-term efficacy, and the adverse events are controllable.
大多数接受嵌合抗原受体 T 细胞（CAR-T）治疗的复发或难治性 B 细胞淋巴母细胞白血病（R/R B-ALL）患者可获得早期缓解，但部分患者会复发。CAR-T 细胞治疗后尚无共识的治疗策略。在这项针对人源化 CD19 靶向 CAR-T 细胞（hCART19s）治疗 R/R B-ALL 的回顾性研究中，我们分析了接受异基因造血干细胞移植（allo-HSCT）或接受第二次 hCART19s 输注的患者，并总结了他们的疗效和安全性。我们回顾性研究了 2016 年至 2020 年在徐州医科大学附属医院接受 hCART19s 治疗的 28 例 R/R B-ALL 患者。第一次 hCART19s 输注后，10 例患者接受 allo-HSCT（CART+HSCT 组），7 例患者接受第二次 hCART19s 输注（CART2 组），11 例患者未接受 HSCT 或第二次 hCART19s 输注（CART1 组）。分析了安全性、疗效和长期生存情况。在接受 hCART19s 治疗的 28 例患者中，1 例患者无法评估疗效，25 例（92.6%）患者达到完全缓解（CR），其中 20 例（74.7%）患者达到微小残留病（MRD）阴性。7 例（25%）患者发生 3-4 级细胞因子释放综合征（CRS），1 例患者死于 5 级 CRS。无患者发生≥3 级免疫效应细胞相关神经毒性综合征（ICANS）。与 CART2 组相比，CART+HSCT 组第二次 CR 的发生率更高（100% vs. 42.9%，p=0.015）。中位随访时间为 1240 天（范围：709-1770 天）。与 CART2 组（中位 OS：482 天；中位 LFS：189 天）和 CART1 组（中位 OS：236 天；中位 LFS：35 天）相比，CART+HSCT 组的总生存期（OS）和无白血病生存期（LFS）明显更长（中位 OS：未达到，p=0.006；中位 LFS：未达到，p=0.001）。在 CART+HSCT 组中，急性移植物抗宿主病（aGVHD）的发生率为 30%（3/10），移植相关死亡率为 30%（3/10）。无慢性移植物抗宿主病发生。多因素分析结果表明，骨髓中 blast≥20%和 MRD≥65.6%是 OS 和 LFS 预后不良的独立因素，而接受 allo-HSCT 是 OS 和 LFS 延长的独立因素。总之，CAR-T 治疗后早期进行 allo-HSCT 可获得长期疗效，且不良反应可控制。
