Abstract：
BACKGROUND: CARTITUDE-2 (NCT04133636) Cohort B is evaluating cilta-cel in patients with MM and early relapse after initial therapy. These patients have functionally high-risk disease and unmet medical needs, as early relapse post-ASCT is associated with a poor prognosis.
OBJECTIVE: To present updated results from CARTITUDE-2 Cohort B.
METHODS: Phase 2, multicohort study.
METHODS: Eligible patients had MM, 1 prior LOT (PI and IMiD required), disease progression per IMWG, and no previous treatment with CAR-T/anti-BCMA therapies.
METHODS: Single cilta-cel infusion (target dose 0.75×106 CAR+ viable T-cells/kg) post lymphodepletion.
METHODS: Safety and efficacy were evaluated. Primary endpoint was MRD negativity at 10-5. Management strategies were used to reduce the risk of movement/neurocognitive AEs (MNTs). Assessments included pharmacokinetics (PK) (Cmax, Tmax of CAR+ T-cell transgene levels in blood), CRS-related cytokine (eg, IL-6) levels over time, peak cytokine levels by response and CRS, association of cytokine levels with ICANS, and CAR+ T-cell CD4/CD8 ratio by response, CRS, and ICANS.
RESULTS: As of January 2022 (median follow-up 13.4 months), 19 patients (median age 58.0 years; 74% male; 79% with prior ASCT) received cilta-cel. ORR was 100% (90% ≥CR and 95% ≥VGPR). Median time to first response was 0.95 months and median time to best response was 5.1 months. Median DOR was not reached. Of 15 MRD-evaluable patients, 14 (93%) achieved MRD 10-5 negativity. At 12 months, the event-free rate was 88.9% and PFS rate was 90%. CRS occurred in 16 (84.2%) patients (1 gr 4); median time to onset was 8 days. CRS resolved in all patients. 1 patient had ICANS (gr 1); 1 patient had MNT (gr 3; previously reported). 1 death occurred post-cilta-cel due to progressive disease (day 158). Preliminary PK data showed CAR-T cell peak expansion on day 13.1 and median persistence was 76.9 days.
CONCLUSIONS: A single cilta-cel infusion resulted in deep and durable responses and manageable safety in functionally high-risk patients with MM and early clinical relapse/treatment failure to initial therapy. We will present updated and detailed PK/cytokine/CAR-T subset analyses and clinical correlations to provide novel insights into biological correlates of efficacy/safety in this population.
OBJECTIVE: To present updated results from CARTITUDE-2 Cohort B.
METHODS: Phase 2, multicohort study.
METHODS: Eligible patients had MM, 1 prior LOT (PI and IMiD required), disease progression per IMWG, and no previous treatment with CAR-T/anti-BCMA therapies.
METHODS: Single cilta-cel infusion (target dose 0.75×106 CAR+ viable T-cells/kg) post lymphodepletion.
METHODS: Safety and efficacy were evaluated. Primary endpoint was MRD negativity at 10-5. Management strategies were used to reduce the risk of movement/neurocognitive AEs (MNTs). Assessments included pharmacokinetics (PK) (Cmax, Tmax of CAR+ T-cell transgene levels in blood), CRS-related cytokine (eg, IL-6) levels over time, peak cytokine levels by response and CRS, association of cytokine levels with ICANS, and CAR+ T-cell CD4/CD8 ratio by response, CRS, and ICANS.
RESULTS: As of January 2022 (median follow-up 13.4 months), 19 patients (median age 58.0 years; 74% male; 79% with prior ASCT) received cilta-cel. ORR was 100% (90% ≥CR and 95% ≥VGPR). Median time to first response was 0.95 months and median time to best response was 5.1 months. Median DOR was not reached. Of 15 MRD-evaluable patients, 14 (93%) achieved MRD 10-5 negativity. At 12 months, the event-free rate was 88.9% and PFS rate was 90%. CRS occurred in 16 (84.2%) patients (1 gr 4); median time to onset was 8 days. CRS resolved in all patients. 1 patient had ICANS (gr 1); 1 patient had MNT (gr 3; previously reported). 1 death occurred post-cilta-cel due to progressive disease (day 158). Preliminary PK data showed CAR-T cell peak expansion on day 13.1 and median persistence was 76.9 days.
CONCLUSIONS: A single cilta-cel infusion resulted in deep and durable responses and manageable safety in functionally high-risk patients with MM and early clinical relapse/treatment failure to initial therapy. We will present updated and detailed PK/cytokine/CAR-T subset analyses and clinical correlations to provide novel insights into biological correlates of efficacy/safety in this population.
摘要：
背景：CARTITUDE-2（NCT04133636）队列B正在评估初始治疗后早期复发的MM患者的纤溶细胞。这些患者具有功能性高风险疾病和未满足的医疗需求，ASCT后早期复发与不良预后相关。
目的：介绍CARTITUDE-2队列B的最新结果。
方法：2期，多队列研究。
方法：符合条件的患者患有MM，1之前的LOT（需要PI和IMiD），根据IMWG的疾病进展，以前没有使用CAR-T/抗BCMA治疗。
方法:淋巴清除后单次细胞输注(目标剂量0.75×106CAR+活T细胞/kg)。
方法：评估安全性和有效性。主要终点是10-5的MRD阴性。使用管理策略来降低运动/神经认知AE（MNT）的风险。评估包括药代动力学（PK）（Cmax，血液中CAR+T细胞转基因水平的Tmax），CRS相关细胞因子（例如，IL-6)水平随时间变化，响应和CRS的峰值细胞因子水平，细胞因子水平与ICANS的关联，和CAR+T细胞CD4/CD8比值，CRS,和ICANS。
结果：截至2022年1月（中位随访13.4个月），19例患者（中位年龄58.0岁；74％为男性；79％有先前的ASCT）接受了cilta-cel。ORR为100%(90%≥CR和95%≥VGPR)。首次反应的中位时间为0.95个月，最佳反应的中位时间为5.1个月。未达到中值DOR。在15名可MRD评估的患者中，14（93%）达到MRD10-5负。12个月时,无事件率为88.9%,PFS率为90%.16例（84.2%）患者（1gr4）发生CRS；中位发病时间为8天。CRS在所有患者中得到解决。1例患者有ICANS（gr1）；1例患者有MNT（gr3；先前报告）。1例由于进行性疾病而在cilta-cel后死亡(第158天)。初步PK数据显示在第13.1天的CAR-T细胞峰值扩增,并且中位持久性为76.9天。
结论：在功能高风险的MM患者和早期临床复发/治疗失败的初始治疗中，单次cilta-cel输注导致深度和持久的反应和可控的安全性。我们将提供更新和详细的PK/细胞因子/CAR-T子集分析和临床相关性，以提供对该人群中功效/安全性的生物学相关性的新见解。
目的：介绍CARTITUDE-2队列B的最新结果。
方法：2期，多队列研究。
方法：符合条件的患者患有MM，1之前的LOT（需要PI和IMiD），根据IMWG的疾病进展，以前没有使用CAR-T/抗BCMA治疗。
方法:淋巴清除后单次细胞输注(目标剂量0.75×106CAR+活T细胞/kg)。
方法：评估安全性和有效性。主要终点是10-5的MRD阴性。使用管理策略来降低运动/神经认知AE（MNT）的风险。评估包括药代动力学（PK）（Cmax，血液中CAR+T细胞转基因水平的Tmax），CRS相关细胞因子（例如，IL-6)水平随时间变化，响应和CRS的峰值细胞因子水平，细胞因子水平与ICANS的关联，和CAR+T细胞CD4/CD8比值，CRS,和ICANS。
结果：截至2022年1月（中位随访13.4个月），19例患者（中位年龄58.0岁；74％为男性；79％有先前的ASCT）接受了cilta-cel。ORR为100%(90%≥CR和95%≥VGPR)。首次反应的中位时间为0.95个月，最佳反应的中位时间为5.1个月。未达到中值DOR。在15名可MRD评估的患者中，14（93%）达到MRD10-5负。12个月时,无事件率为88.9%,PFS率为90%.16例（84.2%）患者（1gr4）发生CRS；中位发病时间为8天。CRS在所有患者中得到解决。1例患者有ICANS（gr1）；1例患者有MNT（gr3；先前报告）。1例由于进行性疾病而在cilta-cel后死亡(第158天)。初步PK数据显示在第13.1天的CAR-T细胞峰值扩增,并且中位持久性为76.9天。
结论：在功能高风险的MM患者和早期临床复发/治疗失败的初始治疗中，单次cilta-cel输注导致深度和持久的反应和可控的安全性。我们将提供更新和详细的PK/细胞因子/CAR-T子集分析和临床相关性，以提供对该人群中功效/安全性的生物学相关性的新见解。
