Ixazomib Plus Daratumumab and Dexamethasone: Final Analysis of a Phase 2 Study Among Patients With Relapsed/Refractory Multiple Myeloma

Authors

Sosana Delimpasi
Meletios A Dimopoulos
Jan Straub
Argiris Symeonidis
Luděk Pour
Roman Hájek
Cyrille Touzeau
Viralkumar K Bhanderi
Jesus G Berdeja
Petr Pavlíček
Jeffrey V Matous
Pawel J Robak
Kaveri Suryanarayan
Alison Miller
Miguel Villarreal
Dasha Cherepanov
Jaydeep K Srimani
Huilan Yao
Richard Labotka
Robert Z Orlowski

Publication Date

9-1-2024

Journal

American Journal of Hematology

DOI

10.1002/ajh.27382

PMID

38856176

Abstract

Novel therapies have improved outcomes for multiple myeloma (MM) patients, but most ultimately relapse, making treatment decisions for relapsed/refractory MM (RRMM) patients increasingly challenging. We report the final analysis of a single-arm, phase 2 study evaluating the oral proteasome inhibitor (PI) ixazomib combined with daratumumab and dexamethasone (IDd; NCT03439293). Sixty-one RRMM patients (ixazomib/daratumumab-naïve; 1-3 prior therapies) were enrolled to receive IDd (28-day cycles) until disease progression/unacceptable toxicity. Median age was 69 years; 14.8% of patients had International Staging System stage III disease; 14.8% had received three prior therapies. Patients received a median of 16 cycles of IDd. In 59 response-evaluable patients, the overall response rate was 64.4%; the confirmed ≥very good partial response (VGPR) rate (primary endpoint) was 30.5%. Rates of ≥VGPR in patient subgroups were: high-risk cytogenetics (n = 15, 26.7%), expanded high-risk cytogenetics (n = 24, 29.2%), aged ≥75 years (n = 12, 16.7%), lenalidomide-refractory (n = 21, 28.6%), and prior PI/IMiD therapy (n = 58, 31.0%). With a median follow-up of 31.6 months, median progression-free survival was 16.8 months (95% confidence interval: 10.1-23.7). Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 54.1% of patients; 44.3% had serious TEAEs; TEAEs led to dose modifications/reductions/discontinuations in 62.3%/36.1%/16.4%. There were five on-study deaths. Any-grade and grade ≥3 peripheral neuropathy occurred in 18.0% and 1.6% of patients. Quality of life was generally maintained throughout treatment. IDd showed a positive risk-benefit profile in RRMM patients and was active in clinically relevant subgroups with no new safety signals.

Keywords

Humans, Aged, Multiple Myeloma, Boron Compounds, Male, Female, Antineoplastic Combined Chemotherapy Protocols, Middle Aged, Dexamethasone, Antibodies, Monoclonal, Glycine, Aged, 80 and over, Recurrence

Published Open-Access

yes

Recommended Citation

Delimpasi, Sosana; Dimopoulos, Meletios A; Straub, Jan; et al., "Ixazomib Plus Daratumumab and Dexamethasone: Final Analysis of a Phase 2 Study Among Patients With Relapsed/Refractory Multiple Myeloma" (2024). Faculty, Staff and Student Publications. 4929.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4929