A Phase I Study of Selinexor Combined with Weekly Carfilzomib and Dexamethasone in Relapsed/Refractory Multiple Myeloma.
Benjamin A DermanAjai ChariJeffrey ZonderAjay MajorAndrew T StefkaKen JiangTheodore KarrisonJagoda JasielecAndrzej JakubowiakPublished in: European journal of haematology (2023)
We performed a phase I study of weekly selinexor, carfilzomib, and dexamethasone (wSKd) in patients with relapsed/refractory multiple myeloma (MM). The primary objective was to identify the maximum tolerated dose (MTD) of wSKd. Secondary endpoints included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Prior exposure/refractoriness to carfilzomib was permitted. Thirty patients were enrolled; 26 (87%) had triple-class exposed disease and 6 (20%) received CAR T-cell therapy. Dose level 2 (carfilzomib 70 mg/m 2 IV on days 1, 8, and 15; selinexor 100 mg PO on days 1, 8, 15, 22; dexamethasone 40 mg on days 1, 8, 15, 22 of 28-day cycles) was chosen as the MTD, with no DLTs having occurred. The most common hematologic adverse events (AE) were thrombocytopenia (83%), anemia (70%), lymphopenia (50%), and neutropenia (50%). The most common non-hematologic AE were fatigue (70%), nausea (70%), diarrhea (53%), and anorexia (47%). The ORR was 21/30 (70%) overall and 18/23 (78%) at the MTD. At a median follow-up of 12.3 months, the median PFS was 5.3 months and median OS 23.3 months. Responses were similar in carfilzomib naïve and exposed patients. Long-term efficacy of wSKd is modest; wSKd could be employed as a bridging strategy to immunotherapies. This article is protected by copyright. All rights reserved.
Keyphrases
- sleep quality
- multiple myeloma
- end stage renal disease
- cell therapy
- chronic kidney disease
- free survival
- ejection fraction
- newly diagnosed
- low dose
- high dose
- stem cells
- acute lymphoblastic leukemia
- acute myeloid leukemia
- prognostic factors
- mesenchymal stem cells
- diffuse large b cell lymphoma
- clostridium difficile
- iron deficiency