TY - JOUR
T1 - A phase I study of selinexor combined with weekly carfilzomib and dexamethasone in relapsed/refractory multiple myeloma
AU - Derman, Benjamin A.
AU - Chari, Ajai
AU - Zonder, Jeffrey
AU - Major, Ajay
AU - Stefka, Andrew T.
AU - Jiang, Ken
AU - Karrison, Theodore
AU - Jasielec, Jagoda
AU - Jakubowiak, Andrzej
N1 - Funding Information:
The authors thank the patients and their families for participating in this study. The authors thank Luis Alcantar, Evangelia Andreatos, Christine Gleason, Martha Gorski, Bernadette Libao, Sarah Major, Allison Marthaler, Amanda McIver, Megan Whelan, and Brittany Wolfe at the University of Chicago for their assistance in conducting this study. This study was supported, in part, by Amgen and Karyopharm. The funders were involved in the design of the study. The funders had no role in the collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; nor decision to submit the manuscript for publication.
Funding Information:
The authors thank the patients and their families for participating in this study. The authors thank Luis Alcantar, Evangelia Andreatos, Christine Gleason, Martha Gorski, Bernadette Libao, Sarah Major, Allison Marthaler, Amanda McIver, Megan Whelan, and Brittany Wolfe at the University of Chicago for their assistance in conducting this study. This study was supported, in part, by Amgen and Karyopharm. The funders were involved in the design of the study. The funders had no role in the collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; nor decision to submit the manuscript for publication.
Publisher Copyright:
© 2023 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.
PY - 2023/5
Y1 - 2023/5
N2 - 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.
AB - 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.
KW - clinical trial
KW - multiple myeloma
KW - phase I
UR - http://www.scopus.com/inward/record.url?scp=85148363585&partnerID=8YFLogxK
U2 - 10.1111/ejh.13937
DO - 10.1111/ejh.13937
M3 - Article
C2 - 36726221
AN - SCOPUS:85148363585
SN - 0902-4441
VL - 110
SP - 564
EP - 570
JO - European Journal of Haematology
JF - European Journal of Haematology
IS - 5
ER -