Multiple Myeloma

Ixazomib as Postinduction Maintenance for Patients With Newly Diagnosed Multiple Myeloma Not Undergoing Autologous Stem Cell Transplantation: The Phase III TOURMALINE-MM4 Trial

In the December 1, 2020 edition of Journal of Clinical Oncology, Meletios A. Dimopoulos and colleagues report on the results of the Phase III TOURMALINE-MM4 Trial.

PURPOSE

The role of ixazomib in the maintenance setting for multiple myeloma, in patients who are not candidates for autologous stem cell transplantation, was determined in the study.

PATIENTS AND METHODS

Investigators conducted a phase III, double-blind, placebo-controlled TOURMALINE-MM4 study were newly diagnosed multiple myeloma patients, not undergoing autologous stem cell transplantation, or randomized in a 3:2 fashion, after achieving better than or equal to a partial response after 6-12 months of induction treatment to either ixazomib or placebo on days 1, 8, and 15 of 28-day cycles as maintenance for 24 months. The primary endpoint was PFS.

RESULTS

Patients were randomized to either ixazomib (n = 425) or placebo (n = 281). TOURMALINE-MM4 met its primary endpoint with a 34.1% reduction in risk of progression or death with ixazomib versus placebo (median PFS , 17.4 v 9.4 months; HR, 0.659; 95% CI, 0.542 to 0.801; P < .001; median follow-up, 21.1 months). Ixazomib was shown to significantly benefit patients who achieved complete or very good partial response after induction therapy (median PFS, 25.6 v 12.9 months; HR, 0.586; P < .001).  When comparing ixazomib versus placebo, 36.6% versus 23.2% of patients who had grade ≥ 3 treatment-emergent adverse events (TEAEs); 12.9% versus 8.0% who had to discontinue treatment because of TEAEs. Common grade 1-4 TEAEs included nausea (26.8% v 8.0%), vomiting (24.2% v 4.3%), and diarrhea (23.2% v 12.3%). There was no documented increase in any new primary malignancies (5.2% v 6.2%); rates of on-study deaths were 2.6% versus 2.2%.

The authors concluded “Ixazomib maintenance prolongs PFS with no unexpected toxicity in patients with NDMM not undergoing ASCT. To our knowledge, this is the first PI demonstrated in a randomized clinical trial to have single-agent efficacy for maintenance and is the first oral PI option in this patient population.”

Reference:

Ixazomib as Postinduction Maintenance for Patients With Newly Diagnosed Multiple Myeloma Not Undergoing Autologous Stem Cell Transplantation: The Phase III TOURMALINE-MM4 Trial

https://ascopubs.org/doi/full/10.1200/JCO.20.02060

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