Abstract：
BACKGROUND: Cilta-cel, a CAR-T cell therapy with 2 BCMA-targeting single-domain antibodies, led to early, deep, and durable responses in heavily pretreated patients with RRMM in the phase 1b/2 CARTITUDE-1 study (NCT03548207).
OBJECTIVE: To report updated results from CARTITUDE-1. Data 2-years post LPI (~30-month median follow-up [MFU]) will be presented; here we report results at 21.7-month MFU.
METHODS: Eligible patients with RRMM had ≥3 prior lines of therapy (LOT) or were refractory to a proteasome inhibitor (PI) and immunomodulatory drug (IMiD) and had received a PI, IMiD, and anti-CD38 antibody.
METHODS: After apheresis, bridging therapy was allowed. A single infusion of cilta-cel (target dose 0.75×106 CAR+ viable T cells/kg) was administered 5-7 days after lymphodepletion.
METHODS: Cilta-cel safety and efficacy were the primary objectives. Assessments included response (per IMWG criteria by independent review committee) and minimal residual disease (MRD) negativity (at 10-5 by next-generation sequencing).
RESULTS: As of July 22, 2021, 97 patients (59% male; median age 61 years; median 6 [range 3-18] prior LOT) received cilta-cel. Overall response rate was 97.9% (94.9% very good partial response; 82.5% stringent complete response). Median times to first response, best response, and ≥complete response were 1.0, 2.6, and 2.9 months, respectively. Median duration of response was not reached. Among 61 MRD-evaluable patients, 92% were MRD negative (10-5), sustained for ≥6 months in 44% and ≥12 months in 18%. Progression-free survival (PFS) at 2 years was 60.5%. Median PFS and overall survival were not reached. PFS rates at 2 years in patients with MRD negativity sustained for ≥6 months and ≥12 months were 91% and 100%, respectively. No new safety signals, new events of CAR-T cell neurotoxicity, movement and neurocognitive treatment-emergent adverse events, or treatment-related deaths have occurred since 1-year MFU. Over ~2 years MFU, 15 second, primary malignancies were reported in 11 patients.
CONCLUSIONS: At ~2 years MFU, a single infusion of cilta-cel resulted in deepening and durable responses and manageable safety in heavily pretreated patients with RRMM. Additional research is ongoing to evaluate cilta-cel in earlier LOT and outpatient settings across the CARTITUDE program (NCT04133636, NCT04181827, NCT04923893).
OBJECTIVE: To report updated results from CARTITUDE-1. Data 2-years post LPI (~30-month median follow-up [MFU]) will be presented; here we report results at 21.7-month MFU.
METHODS: Eligible patients with RRMM had ≥3 prior lines of therapy (LOT) or were refractory to a proteasome inhibitor (PI) and immunomodulatory drug (IMiD) and had received a PI, IMiD, and anti-CD38 antibody.
METHODS: After apheresis, bridging therapy was allowed. A single infusion of cilta-cel (target dose 0.75×106 CAR+ viable T cells/kg) was administered 5-7 days after lymphodepletion.
METHODS: Cilta-cel safety and efficacy were the primary objectives. Assessments included response (per IMWG criteria by independent review committee) and minimal residual disease (MRD) negativity (at 10-5 by next-generation sequencing).
RESULTS: As of July 22, 2021, 97 patients (59% male; median age 61 years; median 6 [range 3-18] prior LOT) received cilta-cel. Overall response rate was 97.9% (94.9% very good partial response; 82.5% stringent complete response). Median times to first response, best response, and ≥complete response were 1.0, 2.6, and 2.9 months, respectively. Median duration of response was not reached. Among 61 MRD-evaluable patients, 92% were MRD negative (10-5), sustained for ≥6 months in 44% and ≥12 months in 18%. Progression-free survival (PFS) at 2 years was 60.5%. Median PFS and overall survival were not reached. PFS rates at 2 years in patients with MRD negativity sustained for ≥6 months and ≥12 months were 91% and 100%, respectively. No new safety signals, new events of CAR-T cell neurotoxicity, movement and neurocognitive treatment-emergent adverse events, or treatment-related deaths have occurred since 1-year MFU. Over ~2 years MFU, 15 second, primary malignancies were reported in 11 patients.
CONCLUSIONS: At ~2 years MFU, a single infusion of cilta-cel resulted in deepening and durable responses and manageable safety in heavily pretreated patients with RRMM. Additional research is ongoing to evaluate cilta-cel in earlier LOT and outpatient settings across the CARTITUDE program (NCT04133636, NCT04181827, NCT04923893).
摘要：
背景：Cilta-cel，具有2个BCMA靶向单结构域抗体的CAR-T细胞疗法，导致早期，深,在1b/2CARTITUDE-1期研究（NCT03548207）中，严重预处理的RRMM患者的持续反应。
目的：报告CARTITUDE-1的最新结果。将提供LPI后2年的数据（约30个月的中位随访[MFU]）；在这里我们报告21.7个月MFU的结果。
方法：符合条件的RRMM患者先前有3种治疗（LOT）或对蛋白酶体抑制剂（PI）和免疫调节药物（IMiD）难以治疗，并接受了PI，IMiD,和抗CD38抗体。
方法：单采血液成分后，允许桥接治疗.在淋巴清除后5-7天施用cilta-cel(目标剂量0.75X106CAR+活T细胞/kg)的单次输注。
方法：Cilta-cel安全性和有效性是主要目标。评估包括反应（根据独立审查委员会的IMWG标准）和微小残留病（MRD）阴性（通过下一代测序在10-5）。
结果：截至2021年7月22日，97例患者（59％为男性；中位年龄61岁；中位年龄6[范围3-18]以前的LOT）接受了cilta-cel。总应答率为97.9%(94.9%非常好的部分应答;82.5%严格完全应答)。第一反应的中位数时间，最佳回应,≥完全缓解分别为1.0、2.6和2.9个月，分别。未达到反应持续时间的中位数。在61名可MRD评估的患者中，92%为MRD阴性（10-5），44%的患者持续≥6个月，18%的患者持续≥12个月。2年无进展生存率（PFS）为60.5%。未达到PFS中位数和总生存期。MRD阴性持续≥6个月和≥12个月的患者2年PFS率分别为91%和100%，分别。没有新的安全信号,CAR-T细胞神经毒性的新事件，运动和神经认知治疗引起的不良事件，自1年MFU以来，发生了与治疗相关的死亡。超过2年MFU，15秒,11例患者报告了原发性恶性肿瘤.
结论：在〜2年的MFU，单次输注cilta-cel可导致严重预处理的RRMM患者的反应加深和持久，安全性可控。正在进行其他研究，以评估CARTITUDE计划（NCT04133636，NCT04181827，NCT04923893）的早期LOT和门诊设置中的cilta-cel。
目的：报告CARTITUDE-1的最新结果。将提供LPI后2年的数据（约30个月的中位随访[MFU]）；在这里我们报告21.7个月MFU的结果。
方法：符合条件的RRMM患者先前有3种治疗（LOT）或对蛋白酶体抑制剂（PI）和免疫调节药物（IMiD）难以治疗，并接受了PI，IMiD,和抗CD38抗体。
方法：单采血液成分后，允许桥接治疗.在淋巴清除后5-7天施用cilta-cel(目标剂量0.75X106CAR+活T细胞/kg)的单次输注。
方法：Cilta-cel安全性和有效性是主要目标。评估包括反应（根据独立审查委员会的IMWG标准）和微小残留病（MRD）阴性（通过下一代测序在10-5）。
结果：截至2021年7月22日，97例患者（59％为男性；中位年龄61岁；中位年龄6[范围3-18]以前的LOT）接受了cilta-cel。总应答率为97.9%(94.9%非常好的部分应答;82.5%严格完全应答)。第一反应的中位数时间，最佳回应,≥完全缓解分别为1.0、2.6和2.9个月，分别。未达到反应持续时间的中位数。在61名可MRD评估的患者中，92%为MRD阴性（10-5），44%的患者持续≥6个月，18%的患者持续≥12个月。2年无进展生存率（PFS）为60.5%。未达到PFS中位数和总生存期。MRD阴性持续≥6个月和≥12个月的患者2年PFS率分别为91%和100%，分别。没有新的安全信号,CAR-T细胞神经毒性的新事件，运动和神经认知治疗引起的不良事件，自1年MFU以来，发生了与治疗相关的死亡。超过2年MFU，15秒,11例患者报告了原发性恶性肿瘤.
结论：在〜2年的MFU，单次输注cilta-cel可导致严重预处理的RRMM患者的反应加深和持久，安全性可控。正在进行其他研究，以评估CARTITUDE计划（NCT04133636，NCT04181827，NCT04923893）的早期LOT和门诊设置中的cilta-cel。
