Conference Correspondent

Two Different Doses of Ixazomib in Patients with Relapsed MM Not Refractory to Bortezomib

Conference Correspondent 

Kumar and colleagues reported results of a randomized phase 2 trial that evaluated the efficacy and tolerability of 2 doses of the novel, orally bioavailable proteasome inhibitor (PI) ixazomib, the 5.5-mg dose previously used in monotherapy trials versus the 4-mg dose used in combination trials, in combination with dexamethasone in patients with relapsed multiple myeloma (MM).1 A total of 71 patients received ixazomib 4 mg or 5.5 mg on days 1, 8, and 15 for 3 weeks with 1 week off, on each 28-day cycle, plus weekly dexamethasone (40 mg); eligible patients must have been PI-naive (including bortezomib) or have received <6 cycles of therapy with bortezomib and achieved a ≥partial response.

The study population had received a median of 4 prior therapies; the majority of patients had received prior immunomodulatory drugs (89%-94%) and prior transplant (69%-74%), whereas 29% to 34% had received prior bortezomib. The overall response rates were higher in the ixazomib 5.5-mg cohort compared with the 4-mg cohort (51% vs 31%); however, the median duration of response (16.3 months vs 16.7 months) and median event-free survival (6.9 months vs 8.4 months) were similar. The time to response was slightly shorter in the ixazomib 5.5-mg group (1.0 months) vs the 4.0-mg group (1.4 months).

A higher rate of grade 3/4 adverse events (AEs) that were possibly treatment-related were reported in patients treated with ixazomib 5.5 mg (54% vs 21% with 4-mg dose), of which 37% and 15% were hematologic, respectively, and 29% and 6% were nonhematologic, respectively. The most common AEs included fatigue, thrombocytopenia, diarrhea, and nausea. Peripheral neuropathy (PN) was reported in 55% (all grade 1/2) of patients treated with ixazomib 4 mg, and in 43% of patients (2 patients with grade 3 PN) treated with the 5.5-mg dose. Higher rates of dose reductions due to AEs also occurred in patients who received ixazomib 5.5 mg (43% vs 17%). Based on the study results, the authors concluded that ixazomib plus dexamethasone therapy was well-tolerated and showed antimyeloma activity in patients with relapsed MM, and that the 5.5-mg dose resulted in higher response rates but also higher rates of AEs requiring dose reductions. Thus, when used as an ixazomib/dexamethasone combination it is reasonable to consider the 5.5-mg dose with dose reductions as dictated by toxicity.

  1. Kumar SK, et al. ASH 2015. Abstract 3050.

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