Dr Mikhael on the Utility of Isa-KRd in Newly Diagnosed Multiple Myeloma

Joseph Mikhael, MD, professor, Applied Cancer Research and Drug Discovery Division, the Translational Genomics Research Institute, City of Hope Cancer Center; chief medical officer, theInternational Myeloma Foundation; consultant hematologist, director, Myeloma Research, HonorHealth Research Institute, discusses the utility of isatuximab-irfc (Sarclisa), carfilzomib (Kyprolis), lenalidomide (Revlimid), and dexamethasone (Isa-KRd) in patients with newly diagnosed multiple myeloma, as observed in the phase 3 IsKia trial (NCT04483739).

Findings from the clinical trial were presented at the 2023 ASH Annual Meeting. Data from the study demonstrated increased rates of minimal residual disease (MRD) negativity at the 10^–5 and 10^–6 cutoffs post-consolidation with the use of Isa-KRd vs KRd alone in this newly diagnosed patient population.

The IsKia trial held importance within the myeloma treatment community for several reasons, Mikhael begins. Firstly, it reinforced the trend observed in other trials indicating that using 4 drugs is superior to using 3, especially as an induction regimen before autologous stem cell transplant (ASCT), he explains. The trial also explored this quadruplet regimen in patients not undergoing transplant, expanding the potential impact of these findings, Mikhael notes. Another notable aspect of IsKia was the use of MRD status as the primary end point of the study, diverging from the typical focus on progression-free survival (PFS) in large phase 3 trials, he states.

Although prolonging PFS remains crucial for patients with multiple myeloma, MRD negativity is viewed as a surrogate marker for future PFS and overall survival outcomes, Mikhael expands. Additionally, the study’s incorporation of the quadruplet regimen post-ASCT highlighted the possibility for flexibility in consolidation strategies, the duration of consolidation cycles, and the transition into the maintenance phase, Mikhael explains.

There’s still much to learn regarding the optimal administration of these 4 drugs, including whether patients should continue 3 of the drugs indefinitely, continue 2 of the drugsindefinitely, or base treatment continuation strategies on MRD status or depth of response, he continues. Tailoring approaches for high-risk vs standard-risk patients is another consideration, according to Mikhael. Studies like IsKia offer insights to address these crucial questions, ensuring patients receive sufficient treatment without undue toxicity, striking a delicate balance between prolonging life and maintaining quality of life, Mikhael concludes.