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Daratumumab plus Ixazomib/Dexamethasone as Second-Line in Multiple Myeloma Patients with Prior Lenalidomide Treatment

Conference Correspondent

The DARIA study is an ongoing phase 2, open-label, single-arm, multicenter study examining the efficacy and safety of daratumumab plus ixazomib with dexamethasone as second-line treatment for patients with relapsed multiple myeloma after initial treatment with lenalidomide, the standard of care for newly diagnosed patients with multiple myeloma.

The study, initiated in December of 2018 with an overall duration of 36 months, aimed to assess whether the combination would result in a significant, sustained response in patients who relapsed after lenalidomide treatment. The therapy consists of 9 cycles of induction treatment and continues with maintenance treatment. The treatment regimen consists of daratumumab administered intravenously at a dose of 16 mg/kg every week for the first 2 cycles, every 2 weeks for the following 4 cycles, and every 4 weeks for the last 3 cycles of daratumumab. Ixazomib is given orally on days 1, 8, and 15 of each cycle, and dexamethasone is dosed at 40 mg and given weekly in 28-day cycles. In the subsequent maintenance period, both daratumumab and ixazomib are given every 4 weeks, and continued unless patients experienced toxicity or progression of disease.

The primary outcome measure of the study is the overall response rate (ORR) to the treatment regimen, which is defined as the proportion of patients who achieve a partial response or better. The study considered outcomes of an ORR of 60% unfavorable, with an early-stopping rule for futility, and an ORR of 80% as promising. If the predefined cutoff is achieved, additional patients will be accrued into the study. The secondary outcome measures include evaluation of the toxicities related to administration of daratumumab or ixazomib, duration of response, time to disease progression measured from first dose in treatment to disease progression, progression-free survival, overall survival, bone resorption and formation, and osteoclast regulation and control, and serum cytokine levels of angiogenin, VEGF, angiopoietin-1, and angiopoietin-2.

Stage 1 enrolled 11 patients, of which 5 patients achieved very good partial response and 3 patients achieved partial response, resulting in an ORR of 73%. Consequently, stage 2 of the trial is proceeding. These results suggest that the regimen of daratumumab plus ixazomib with dexamethasone as a second-line therapy for patients with relapsed multiple myeloma initially treated with a lenalidomide-based regimen show high response rates. The study will continue to assess results to support the efficacy and safety of the combination regimen for patients with relapsing multiple myeloma as first-line therapy.


Reference

  • Abstract and Poster EP973. EHA 2020. June 12, 2020. Daratumumab with ixazomib and dexamethasone in multiple myeloma patients who have received prior treatment with a lenalidomide-based regimen: design and first results of the phase 2 DARIA study.

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