Isatuximab Plus Carfilzomib and Dexamethasone (ISA-Kd) Vs Kd In RRMM (IKEMA): Interim Analysis of A Phase 3, Randomized, Open-Label Study
What is the IKEMA Trial?
The IKEMA trial is a phase III study in which patients with relapsed refractory multiple myeloma who have undergone 1-3 prior lines of therapy that were randomized 3:2. These patients were stratified by number of prior lines and the Revised International Staging System to receive isatuximab, Kyprolis, and dexamethasone (Isa-Kd) or Kyprolis and dexamethasone (Kd).
In this video:
IMF Chief Medical Officer Dr. Joseph Mikhael (City of Hope — Phoenix) explains the methods, results, and conclusion of this interim analysis of the IKEMA study.
The Isa-Kd arm received Isa (10mg/kg intravenously) weekly for 4 weeks, then every 2 weeks. Both arms received Kyprolis (20mg/m2 days 1-2, 56mg/m2 thereafter) twice-weekly for 3 of 4 weeks, and dexamethasone (20mg) twice-weekly. Treatment continued until disease progression or unacceptable adverse events (AE) occurred.
The primary objective of the study was to demonstrate an increase in progression-free survival (PFS) from the use of Isa-Kd as opposed to Kd. The results were determined by an Independent Response Committee (IRC). Comparison between arms conducted through long-rank testing.
The key secondary objectives of the study were to evaluate the overall response rate (ORR), rate of very good partial response (VGPR) or better, complete response (CR) rate, minimal residual disease (MRD) negativity rate (10^5 by NGS), and overall survival (OS). Key secondary endpoints tested with a closed test procedure. Safety data included treatment emergent adverse events (TEAE), and hematology and biochemistry results for all patients. When 65% of the total expected PFS events were observed, interim efficacy analysis was planned.
The addition of isatuximab to Kyprolis and dexamethasone provided a superior, statistically significant improvement in progression-free survival with clinically meaningful improvement in depth of response. Isa-Kd was well tolerated with manageable safety and a favorable benefit-risk profile. This combination represents a possible new standard of care treatment in patients with relapsed multiple myeloma.
Clinical Trial Information: NCT03275285
JOSEPH MIKHAEL, MD
Dr. Joseph Mikhael is a world-renowned multiple myeloma expert. In his position with the IMF, he works closely with the Board Chairman, Dr. Brian G.M. Durie, to advance the mission of the organization in research, education, advocacy, and patient care to improve the lives of patients with myeloma. Dr. Mikhael has conducted dozens of clinical trials in the field of multiple myeloma and has contributed to the development of many novel drugs. He has served as a Professor of Medicine at the Mayo Clinic, an Associate Dean at the Mayo Clinic School of Graduate Medical Education, and as the Deputy Director of Education at the Mayo Clinic Cancer Center. Dr. Mikhael also serves as a councilor on the American Society of Hematology (ASH) Executive Committee and is involved in mentoring the next generation of hematologists. He did his medical training in Canada, having completed medical school at the University of Ottawa, his hematology training at the University of Toronto, and a Multiple Myeloma Fellowship at Princess Margaret Hospital. He also has a master’s degree in education from the University of Toronto. Dr. Mikhael remains in clinical and academic medicine with the City of Hope Cancer Center in California. Visit Dr. Joseph Mikhael’s full biography