A phase I study of selinexor combined with weekly carfilzomib and dexamethasone in relapsed/refractory multiple myeloma

Eur J Haematol. 2023 May;110(5):564-570. doi: 10.1111/ejh.13937. Epub 2023 Feb 15.

Abstract

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 chimeric antigen receptor (CAR) T-cell therapy. Dose level 2 (carfilzomib 70 mg/m2 Intravenous [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 nonhematologic 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.

Keywords: clinical trial; multiple myeloma; phase I.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Dexamethasone
  • Humans
  • Multiple Myeloma* / diagnosis
  • Multiple Myeloma* / drug therapy

Substances

  • carfilzomib
  • selinexor
  • Dexamethasone