San Diego, California—A combination treatment regimen comprised of ixazomib, lenalidomide, dexamethasone, and daratumumab produced rapid and deep responses in patients with newly diagnosed multiple myeloma, according to results from a recent clinical trial presented at the 2018 ASH Annual Meeting.

“The combination of a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and dexamethasone is the current standard induction therapy for myeloma. Daratumumab…is highly effective in treating myeloma and improves response rates and progression free survival (PFS) when added to PI or IMiD,” said Shaji Kumar, MD, Department of Hematology, Mayo Clinic, Rochester, Minnesota, and colleagues.

Citing previous trials demonstrating the efficacy of the combination therapy of ixazomib, lenalidomide, plus dexamethasone, Dr Kumar and colleagues conducted a study to determine the feasibility and efficacy of adding daratumumab to this multi-class regimen. Dr Kumar presented the results of the study at ASH 2018.

A total of 40 treatment-naïve patients with multiple myeloma, measurable disease, and adequate organ function were enrolled in the study, regardless of their transplant eligibility. The median age of the patients was 62 years, and approximately 50% of them were women.

Patients in the study received ixazomib 4 mg on days 1, 8, and 15; lenalidomide 25 mg on days 1 through 21; dexamethasone 40 mg weekly; and daratumumab 16 mg/kg weekly for 2 cycles, every other week during cycles 3 to 6, and then every 4 weeks after that. The primary end point was complete response rate.

Ultimately, as of July 2, 2018, data were only available for analysis from 38 patients.

According to Dr Kumar and colleagues, all patients were alive and free of disease progression free at the last assessment, with a median follow-up of 5.2 months; 1 patient had stopped taking the trial regimen and switched to an alternative therapy.

Responses were rapid for patients who received 2 cycles of the treatment regimen, with 90% having partial responses or better. Similar responses were seen among the 32 patients who completed 4 cycles of therapy, with 100% having partial responses or better.

Among the 38 patients whose data were available for analysis, the overall best confirmed response rate was 95%, including 11% with complete responses and 47% with very good partial responses.

Of the 231 cycles administered across the study population, dose modifications and holds were required for ixazomib, lenalidomide, daratumumab, and dexamethasone in 3 (8%), 11 (29%), 2 (5%), and 8 (21%) patients, respectively. Dose modifications and holds most frequently occurred because of hematologic events and skin rash. Adverse events of grade 3 or higher potentially attributable to the study drugs were seen in 42% of patients; 37% had hematologic events whereas 11% were nonhematologic.

Thus far, 11 patients have moved on to stem-cell collection; all of the patients have collected adequate numbers of stem cells for up to 2 intended transplants.

“The early results from the use of IRd-Dara [ixazomib, lenalidomide, dexamethasone, and daratumumab] in newly diagnosed myeloma suggests excellent efficacy with rapid responses that deepen quickly over the initial cycles of therapy,” Dr Kumar and colleagues concluded.

“The regimen was well tolerated with limited dose modifications and no discontinuation for toxicity and no influence on the ability to collect stem cells,” they said.—Hina Khaliq

Kumar S, Kapoor P, Laplant B, et al. Phase 2 trial of ixazomib, lenalidomide, dexamethasone and daratumumab in patients with newly diagnosed multiple myeloma. Presented at: the 60th ASH Annual Meeting and Exposition; December 1-4, 2018; San Diego, CA. Abstract 304.