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.

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).