BMT & Cellular Therapy Program, Department of Medicine, and.
Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI.
Blood Adv. 2022 Jan 25;6(2):486-494. doi: 10.1182/bloodadvances.2021005788.
Allogeneic transplant (alloHCT) and chimeric antigen receptor modified (CAR)-T cell therapy are potentially cuarative options of diffuse large B-cell lymphoma (DLBCL) relapsing after an autologous (auto)HCT. Although the Center for International Blood and Marrow Transplant Research (CIBMTR) prognostic model can predict outcomes of alloHCT in DLBCL after autoHCT failure, corresponding models of CAR-T treatment in similar patient populations are not available. In this noncomparative registry analysis, we report outcomes of patients with DLBCL (≥18 years) undergoing a reduced intensity alloHCT or CAR-T therapy with axicabtagene ciloleucel during 2012 to 2019 after a prior auto-HCT failure and apply the CIBMTR prognostic model to CAR-T recipients. A total of 584 patients were included. The 1-year relapse, nonrelapse mortality, overall survival (OS), and progression-free survival for CAR-T treatment after autoHCT failure were 39.5%, 4.8%, 73.4%, and 55.7%, respectively. The corresponding rates in the alloHCT cohort were 26.2%, 20.0%, 65.6%, and 53.8%, respectively. The 1-year OS of alloHCT recipients classified as low-, intermediate- and high/very high-risk groups according to the CIBMTR prognostic score was 73.3%, 59.9%, and 46.3%, respectively (P = .002). The corresponding rates for low-, intermediate-, and high/very high-risk CAR-T patients were 88.4%, 76.4%, and 52.8%, respectively (P < .001). This registry analysis shows that both CAR-T and alloHCT can provide durable remissions in a subset of patients with DLBCL relapsing after a prior autoHCT. The simple CIBMTR prognostic score can be used to identify patients at high risk of treatment failure after either procedure. Evaluation of novel relapse mitigations strategies after cellular immunotherapies are warranted in these high-risk patients.
同种异体移植(alloHCT)和嵌合抗原受体修饰(CAR)-T 细胞疗法是自体(auto)HCT 后复发的弥漫性大 B 细胞淋巴瘤(DLBCL)潜在的治愈选择。尽管国际血液和骨髓移植研究中心(CIBMTR)预后模型可以预测 autoHCT 失败后 alloHCT 治疗 DLBCL 的结果,但类似患者人群中 CAR-T 治疗的对应模型尚不可用。在这项非比较性注册分析中,我们报告了 2012 年至 2019 年间,584 例既往 auto-HCT 失败后接受减低强度 alloHCT 或 axicabtagene ciloleucel 治疗的 DLBCL(≥18 岁)患者的结果,并将 CIBMTR 预后模型应用于 CAR-T 治疗的患者。CAR-T 治疗后 autoHCT 失败的 1 年复发率、非复发死亡率、总生存率(OS)和无进展生存率分别为 39.5%、4.8%、73.4%和 55.7%。alloHCT 队列的相应比率分别为 26.2%、20.0%、65.6%和 53.8%。根据 CIBMTR 预后评分,alloHCT 受者分为低、中、高/极高风险组的 1 年 OS 分别为 73.3%、59.9%和 46.3%(P=0.002)。低、中、高/极高风险 CAR-T 患者的相应比例分别为 88.4%、76.4%和 52.8%(P<0.001)。这项注册分析表明,CAR-T 和 alloHCT 都可以为既往 autoHCT 后复发的一部分 DLBCL 患者提供持久缓解。简单的 CIBMTR 预后评分可用于识别两种治疗方法后治疗失败风险较高的患者。在这些高危患者中,有必要评估新型缓解细胞免疫疗法后复发的策略。