Ixazomib-Containing Regimen Boosts Refractory, Relapsed Multiple Myeloma PFS

Progression-free survival benefit reported for triple multiple myeloma regimen containing ixazomib, lenalidomide and dexamethasone

medwireNews: The addition of ixazomib to lenalidomide and dexamethasone significantly extends progression-free survival (PFS) for patients with relapsed and/or refractory multiple myeloma, say the TOURMALINE-MM1 investigators.

All participants of the phase III trial received oral lenalidomide on days 1 to 21 of a 28-day cycle plus dexamethasone on days 1, 8, 15 and 22, explain Philippe Moreau, from University Hospital Hotel Dieu in Nantes, France, and co-workers.

Median PFS was 20.6 months for the 360 patients randomly assigned to also receive a 4 mg dose of the oral Proteasome inhibitor ixazomib on days 1, 8 and 15 compared with 14.7 months for the 362 patients given placebo, with a significant hazard ratio of 0.74.

And a significant gain in PFS with ixazomib versus placebo was also true for all the prespecified patient groups, the team reports in The New England Journal of Medicine.

This included patients with high-risk cytogenetic abnormalities (21.4 vs 9.7 months), patients aged over 75 years old (18.5 vs 13.1 months) and those classified as stage III on the International Staging System (18.4 vs 10.1 months).

A response was reported for 78.3% of ixazomib-treated patients versus 71.5% of controls, a significant difference.

“The responses were rapid and durable and deepened with increasing duration of treatment (i.e., more people had a response and the type of response also got better over time, with more people having a very good partial response or a complete response)”, the researchers comment.

Serious adverse events and deaths were comparable for the ixazomib and placebo treatment groups, affecting 47% versus 49%, and 4% versus 6%, respectively.

Grade 3 or more severe side effects were reported in 74% and 69% of the ixazomib-treated patients and controls, respectively; both grade 3 (12 vs 5%) and grade 4 (7 vs 4%) thrombocytopenia, and rash of any grade (36 vs 23%) were more common with ixazomib.

Peripheral neuropathy of any grade was reported for 27% of patients given ixazomib and 22% of controls, with 2% of both groups experiencing grade 3 events.

Gastrointestinal adverse events were also more common in ixazomib-treated patients but the researchers say these occurred mostly in the first 3 months of treatment, were low-grade and manageable with antidiarrheal or anti-emetic treatment.

Philippe Moreau et al write that the duration of therapy for ixazomib-treated patients was “notable”, with the 23-month analysis showing that almost half the patients had received treatment for at least 18 cycles, as well as comparable high rates of adherence in both treatment groups.

“[T]hese findings suggest that the all-oral ixazomib regimen was as simple and convenient for patients to follow as the placebo regimen”, they say, adding that quality of life outcomes were also similar.

The TOURMALINE-MM1 investigators conclude: “[I]n consideration of its adverse-event profile and efficacy, this all-oral regimen provides an additional therapeutic option for patients with relapsed, refractory, or relapsed and refractory multiple myeloma.”

Reference

Moreau P, Masszi T, Grzasko N, et al. Oral ixazomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med 2016; 374: 1621–1634. DOI: 10.1056/NEJMoa1516282

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