Combining Triplet with Molecularly Targeted Therapy Could Enhance MM Response

The MyDRUG trial successfully identified patients with functional high-risk multiple myeloma (MM) who would benefit from molecularly targeted therapies used in combination with standard triplet regimens, according to Joshua Richter, MD, of Icahn School of Medicine at Mount Sinai in New York, New York, who presented results from one of the trial’s arms.

MyDRUG is a genomically guided umbrella trial that includes patients with functional high-risk disease defined as early relapse after primary therapy. All included patients had specific genetic abnormalities, and those without actionable abnormalities were enrolled in a “nonactionable” arm.

Dr. Richter presented data from the Y3 arm of the trial, which tested selinexor, ixazomib, pomalidomide, and dexamethasone (seli-IPD), an all-oral regimen given on a 28-day cycle.

Seventeen patients were on the Y3 arm. They had a median of two prior lines of therapy and were a median 29 months from diagnosis.

More than half of patients responded to seli-IPD, with an overall response rate of 52.9% and a clinical benefit rate of 58.8%. Median progression-free survival was 10.2 months, and median overall survival has not yet been reached. As of the data cutoff, all patients were still alive.

About half of patients (47.1%) experienced a serious adverse events. Two patients required treatment discontinuation due to adverse events, and two patients required dose reduction.

Overall, the results from the Y3 arm showed that molecularly targeted therapy seli-IPD had “significant efficacy and a manageable adverse event profile,” the authors wrote. They said the all-oral regimen could minimize patient office visits and reduce parenteral therapy administrations.

Reference

Richter J, Zonder JA, Nathwani N, et al. Selinexor, ixazomib, pomalidomide, and dexamethasone in functionally high-risk multiple myeloma: results from the Myeloma Developing Regimens Using Genomics (MyDRUG) Sub-Protocol Y3. Abstract #3387. Presented at the 65th ASH Annual Meeting and Exposition; December 9–12, 2023; San Diego, California.