SAN DIEGO – Ixazomib improved progression-free survival following autologous stem cell transplantation (ASCT) in patients with newly diagnosed multiple myeloma, according to results of a double-blind, randomized, placebo-controlled, phase 3 trial.
Andrew Bowser/MDedge News
Dr. Meletios A. Dimopoulos
Treatment with the oral proteasome inhibitor for 24 months was well tolerated, had a low discontinuation rate, and improved progression-free survival by 39% versus placebo, according to Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens.
These findings suggest ixazomib (Ninlaro) represents a “new treatment option for maintenance after transplantation,” Dr. Dimopoulos said at the annual meeting of the American Society of Hematology.
The trial, known as TOURMALINE-MM3, is the first-ever randomized, double-blind, placebo-controlled study of a proteasome inhibitor used as maintenance after ASCT, according to Dr. Dimopoulos. Lenalidomide is approved in that setting, but 29% of patients who start the treatment discontinue because of treatment-related adverse events.
“Proteasome inhibitors have a different mechanism of action and may provide an alternative to lenalidomide,” Dr. Dimopoulos said at an oral abstract session. Ixazomib has a manageable toxicity profile and “convenient” weekly oral dosing, making it “well suited” for maintenance.
When asked by an attendee whether ixazomib would become “the standard of care” for younger patients with myeloma in this setting, Dr. Dimopoulos replied the results show that ixazomib “is an option for patients, especially for those where a physician may believe that a proteasome inhibitor may be indicated.”
However, when pressed by an attendee to comment on how ixazomib compares with lenalidomide for maintenance, Dr. Dimopoulos remarked that current maintenance studies are moving in the direction of combining therapies.
“I think that instead of saying, ‘is ixazomib better than lenalidomide?’ or vice versa, it is better to see how one may combine those drugs in subsets of patients, or even combine these drugs with other agents,” he said.
The TOURMALINE-MM3 study included 656 patients randomized posttransplantation to receive weekly ixazomib or placebo for up to 2 years.
The median progression-free survival was 26.5 months for ixazomib versus 21.3 months for placebo (P = .002; hazard ratio, 0.720; 95% confidence interval, 0.582-0.890). Median overall survival had not been reached in either ixazomib or placebo arms as of this report, with a median follow-up of 31 months.
The discontinuation rate was 7% for ixazomib versus 5% for placebo, according to the investigator. Moreover, ixazomib was associated with “low toxicity” and no difference in the rates of new primary malignancies, at 3% in both arms.
A manuscript describing results of the TOURMALINE-MM3 study is in press in the Lancet, with an expected online publication date of Dec. 10, Dr. Dimopoulos told attendees. Other studies are ongoing to evaluate ixazomib combinations and treatment to progression in this setting.
TOURMALINE-MM3 is sponsored by Takeda (Millennium), the maker of ixazomib. Dr. Dimopoulos reported honoraria and consultancy with Janssen, Takeda Pharmaceutical, Amgen, Bristol-Myers Squibb, and Celgene.
SOURCE: Dimopoulos MA et al. ASH 2018, Abstract 301.