ABSTRACT Patients with relapsed/refractory multiple myeloma (RRMM) who are penta‐drug refractory, defined as resistant to two proteasome inhibitors, two immunomodulatory agents, and an anti‐CD38 monoclonal antibody, face a dismal prognosis, particularly after exposure to T‐cell–redirecting therapies. Selinexor, an oral exportin‐1 inhibitor, offers a distinct mechanism of action and may retain efficacy in this difficult setting. We conducted a retrospective analysis at six German tertiary centers (2023–2025) to evaluate the efficacy and safety of selinexor plus bortezomib and dexamethasone (SVd) in penta‐refractory MM after both BCMA‐ and GPRC5D‐targeted therapies. Eighteen patients were identified, with a median of seven prior lines of therapy. High‐risk cytogenetic abnormalities were present in seven cases, including del17p in six. The overall response rate (ORR) was 61%, including one complete, five very good partial, and five partial responses, and median progression‐free survival (PFS) was 4.3 months. Among nine patients (50%) with extramedullary disease (EMD), three achieved complete and one near‐complete EMD resolution. Two patients who had relapsed after CAR T‐cell treatment with idecabtagene vicleucel achieved partial and very good partial responses and were successfully transitioned to a second CAR T‐cell therapy with ciltacabtagene autoleucel. Hematologic toxicities under SVd were manageable, and no treatment‐related deaths occurred. SVd demonstrates meaningful activity in patients with penta‐refractory MM and prior failure of BCMA/GPRC5D‐targeted immunotherapies. The ORR of 61%, disease control in 78% of patients, and median PFS of 4.3 months support further evaluation of SVd in this highly refractory setting after failure of BCMA‐ and GPRC5D‐directed approaches.
Al‐Bazaz et al. (Tue,) studied this question.