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.

Clinical Research Takeda Development Center Americas Inc Lexington Massachusetts USA

Colorado Blood Cancer Institute and Sarah Cannon Research Institute Denver Colorado USA

Department of Haematooncology University Hospital Ostrava and Department of Haematooncology Faculty of Medicine University of Ostrava Ostrava Czech Republic

Department of Hematology and Bone Marrow Transplantation Unit General Hospital Evangelismos Athens Greece

Department of Hematology Medical University of Lodz and Copernicus Memorial Hospital Lodz Poland

Department of Hematology University General Hospital of Patras Patras Greece

Department of Internal Medicine and Hematology University Hospital Kralovske Vinohrady Prague Czech Republic

Department of Internal Medicine Hematology and Oncology University Hospital Brno Brno Czech Republic

Department of Internal Medicine Hematology University Hospital Prague Czech Republic

Departments of Lymphoma Myeloma and Experimental Therapeutics The University of Texas MD Anderson Cancer Center Houston Texas USA

Florida Cancer Specialists Tallahassee Cancer Center Tallahassee Florida USA

Global Evidence and Outcomes Lexington Massachusetts USA

Hematology and Medical Oncology Department of Clinical Therapeutics National and Kapodistrian University of Athens School of Medicine Athens Greece

Oncology Clinical Research Takeda Development Center Americas Inc Lexington Massachusetts USA

Oncology Takeda Development Center Americas Inc Lexington Massachusetts USA

Precision and Translational Medicine Takeda Development Center Americas Inc Lexington Massachusetts USA

Quantitative Clinical Pharmacology Takeda Development Center Americas Inc Lexington Massachusetts USA

Sarah Cannon Research Institute Nashville Tennessee USA

Statistics Takeda Development Center Americas Inc Lexington Massachusetts USA

University Hospital Hôtel Dieu Nantes France

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