Locke Frederick L, Siddiqi Tanya, Jacobson Caron A, Nikiforow Sarah, Ahmed Sairah, Miklos David B, Lin Yi, Lunning Matthew A, Hill Brian T, Ghobadi Armin, Hu Zhen-Huan, Hemmer Michael T, Zoratti Michael J, Vunnum Suresh, Tsang Jonathan, Spooner Clare, Smith Harry, Fu Christine, Patel Anik, Miao Harry, Shahani Shilpa A, Mirjah Debbie L, Xu Hairong, Pasquini Marcelo C
Department of Blood and Marrow Transplant and Cellular Immunotherapy, Moffit Cancer Center, Tampa, FL.
Department of Hematology/HCT, City of Hope National Medical Center, Duarte, CA.
Blood Adv. 2025 Jun 10;9(11):2663-2676. doi: 10.1182/bloodadvances.2024013656.
Chimeric antigen receptor (CAR) T-cell products axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), and lisocabtagene maraleucel (liso-cel) are approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Emerging evidence indicates that delayed CAR T-cell infusion, including prolonged time from leukapheresis to infusion, known as vein-to-vein time (V2Vt), may adversely impact clinical outcomes. We conducted a systematic literature review (SLR) and meta-analysis to identify differences in V2Vt in patients with R/R LBCL treated with axi-cel, tisa-cel, or liso-cel. The impact of V2Vt (<28 days vs ≥28 to <40 days vs ≥40 days) on effectiveness and safety outcomes was evaluated in patients treated with axi-cel enrolled in a post-authorization safety study using the Center for International Blood and Marrow Transplant Research data. SLR and meta-analysis showed that patients treated with axi-cel had the shortest median V2Vt (30.6 days) compared with tisa-cel (48.4 days) or liso-cel (35.9 days). Real-world analysis of patients treated with axi-cel demonstrated that V2Vt ≥40 days was associated with significantly lower complete response rate than V2Vt <28 days (odds ratio [OR], 0.61) or ≥28 to <40 days (OR, 0.66) and significantly worse overall survival than V2Vt <28 days (hazard ratio [HR], 1.33) or ≥28 to <40 days (HR, 1.36). Higher prolonged thrombocytopenia rates were observed in patients with axi-cel V2Vt ≥28 to <40 days or ≥40 days compared with <28 days (OR, 1.44 or 1.95, respectively). Together, these results show the impact of V2Vt on patient outcomes with axi-cel therapy and that earlier infusion with CD19-CAR therapies may be beneficial.
嵌合抗原受体(CAR)T细胞产品阿基仑赛(axi-cel)、替雷利珠单抗(tisa-cel)和西罗达基仑赛(liso-cel)已被批准用于复发/难治性(R/R)大B细胞淋巴瘤(LBCL)。新出现的证据表明,CAR T细胞输注延迟,包括从白细胞分离术到输注的时间延长,即所谓的静脉到静脉时间(V2Vt),可能会对临床结果产生不利影响。我们进行了一项系统文献综述(SLR)和荟萃分析,以确定接受axi-cel、tisa-cel或liso-cel治疗的R/R LBCL患者在V2Vt方面的差异。使用国际血液和骨髓移植研究中心的数据,在一项上市后安全性研究中,对接受axi-cel治疗的患者评估了V2Vt(<28天 vs ≥28至<40天 vs ≥40天)对有效性和安全性结果的影响。SLR和荟萃分析表明,与tisa-cel(48.4天)或liso-cel(35.9天)相比,接受axi-cel治疗的患者中位V2Vt最短(30.6天)。对接受axi-cel治疗的患者的真实世界分析表明,V2Vt≥40天与V2Vt<28天(优势比[OR],0.61)或≥28至<40天(OR,0.66)相比,完全缓解率显著降低,总体生存率也显著低于V2Vt<28天(风险比[HR],1.33)或≥28至<40天(HR,1.36)。与<28天相比,axi-cel V2Vt≥28至<40天或≥40天的患者观察到更高的血小板减少延长率(分别为OR,1.44或1.95)。总之,这些结果显示了V2Vt对axi-cel治疗患者结果的影响,并且更早输注CD19-CAR疗法可能有益。