肿瘤细胞治疗研究
英文原题:Lisaftoclax combined with ixazomib and dexamethasone after CAR-T for maintenance therapy in transplant-ineligible relapsed/refractory ultra-high-risk multiple myeloma: two case reports and literature review.
Lisaftoclax combined with ixazomib and dexamethasone after CAR-T for maintenance therapy in transplant-ineligible relapsed/refractory ultra-high-risk multiple myeloma: two case reports and literature review.
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多发性骨髓瘤(MM)是一种无法治愈的恶性肿瘤。治疗主要包括诱导治疗、微小残留病(MRD)清除治疗和维持治疗。对于高危/超高危(UHR)或复发/难治性 MM,如何优化 MRD 清除并长期维持低水平 MRD 抑制,仍是重大挑战。Ixazomib 是一种可逆蛋白酶体抑制剂(PI),可口服其前药 ixazomib citrate。Lisaftoclax 是一种新型、效力强且选择性的 BCL-2 抑制剂,正处于治疗血液系统恶性肿瘤或实体瘤的临床开发阶段,并已显示临床抗肿瘤获益。
本文报告 2 例复发/难治性 UHR MM 患者:在接受靶向 B 细胞成熟抗原(BCMA)的 CAR-T 细胞治疗后,接受 ixazomib、lisaftoclax 和地塞米松(ILD)维持治疗,均实现 MRD 阴性并获得持久疾病控制。方案中所有药物均口服:ixazomib 4 mg,于第 1、8、15 天给药;lisaftoclax 400 mg,于第 1–14 天给药;地塞米松 20 mg,于第 1、8、15 天给药。每个治疗周期为 28 天;若发生无法控制的活动性感染或器官损伤,则停药。这些病例显示 ILD 联合治疗可能优化 MRD 清除并维持长期 MRD 抑制,为治疗选择有限的患者提供有希望的方案。对高危/超高危或复发/难治性 MM 患者正式评估该方案可能具有意义。
本研究获中国癌症基金会支持(项目编号 CFC2023WJZD003)。
Multiple myeloma (MM) is an incurable malignancy. The treatment mainly includes induction therapy, minimal residual disease (MRD) clearance therapy, and maintenance therapy. For high-risk/ultra-high-risk (UHR) or relapsed/refractory MM, optimizing the eradication of MRD and sustaining long-term suppression of MRD at low levels are a formidable challenge.
Ixazomib (I) is a reversible proteasome inhibitor (PI) that is available orally as the prodrug ixazomib citrate. Lisaftoclax is a novel, potent, selective BCL-2 inhibitor under clinical development for the treatment of patients with hematologic malignancies or solid tumors and has shown clinical antitumor benefit.
Herein, we report two patients with relapsed/refractory UHR MM who achieved durable disease control with MRD negativity after receiving ixazomib, lisaftoclax, and dexamethasone (ILD) as maintenance therapy following B Cell Maturity Antigen BCMA-chimeric antigen receptor (CAR)-T cell therapy. Regarding the treatment regimen, all drugs were administered orally: ixazomib 4 mg d1, d8, and d15; lisaftoclax 400 mg d1-d14; and dexamethasone 20 mg d1, d8, and d15.
One treatment cycle is defined as 28 days. Treatment will be discontinued in the event of uncontrollable active infection or organ injury. These cases demonstrate that the ILD combination therapy can optimize MRD eradication and sustain long-term MRD suppression, offering a promising therapeutic option for patients with limited treatment choices. Formal evaluations of this regimen in patients with high-risk/ultra-high-risk or relapsed/refractory MM may be meaningful.
This study was supported by the China Cancer Foundation (Project No. : CFC2023WJZD003).
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