Ixazomib regimen fails to extend PFS in transplant-ineligible multiple myeloma
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The addition of ixazomib to lenalidomide and dexamethasone did not significantly extend PFS among transplant-ineligible patients with newly diagnosed multiple myeloma, according to study results presented at Society of Hematologic Oncology Annual Meeting.
However, the combination significantly prolonged PFS among those with high-risk cytogenetics. It also induced deeper response among all patients regardless of cytogenetics.
“[This combination] is a feasible treatment option for certain transplant-ineligible patients who could benefit from an all-oral triplet combination,” Thierry Facon, MD, professor of hematology at Lille University Hospital in France, and colleagues wrote.
Continuous lenalidomide (Revlimid, Celgene) and dexamethasone-based regimens are standard treatment for transplant-ineligible patients with newly diagnosed multiple myeloma. However, an all-oral triplet may be beneficial for patients who are unable or prefer not to make frequent clinic visits, researchers wrote.
Ixazomib (Ninlaro, Takeda) is an oral proteasome inhibitor approved in the United States for use in combination with lenalidomide and dexamethasone for patients with multiple myeloma who received at least one previous therapy.
The randomized, phase 3 TOURMALINE-MM2 trial included 705 adults with newly diagnosed multiple myeloma who were not candidates for autologous transplant.
Researchers assigned 351 patients (median age, 73 years) to lenalidomide (25 mg on days 1 through 21) and dexamethasone (40 mg weekly) plus ixazomib dosed at 4 mg on days 1, 8 and 15 of each 28-day cycle. The other 354 patients (median age, 74 years) received lenalidomide and dexamethasone plus placebo.
After 18 cycles, dexamethasone was discontinued and doses of ixazomib and lenalidomide were reduced. Treatment continued until disease progression or unacceptable toxicity.
A comparable percentage of patients assigned ixazomib or placebo had International Staging System stage III disease (16% vs. 17%) and high-risk cytogenetics (38% vs. 41%), defined as t(4;14) translocation, t(14;16) translocation or 1q21 amplification.
PFS served as the primary endpoint. Key secondary endpoints included complete response rate, pain response and OS.
Median follow-up was 55.3 months in the ixazomib group and 55.8 months in the placebo group.
Researchers reported numerically longer median PFS among ixazomib-treated patients (35.3 months vs. 21.8 months; HR = 0.83), but the difference did not reach statistical significance.
Overall response rates were comparable between the experimental and control groups (82% vs. 80%). However, a higher percentage of ixazomib-treated patients achieved complete response (26% vs. 14%; OR = 2.1; P < .001), or very good partial response or better (63% vs. 48%; OR = 1.87; P < .001).
Researchers reported longer median time to progression in the ixazomib group (45.8 months vs. 26.8 months; HR = 0.73; P = .008). Median OS did not differ significantly between the ixazomib and placebo groups (57.8 months vs. 58.6 months; HR = 0.99).
Facon and colleagues conducted analyses in the prespecified subgroup of patients with high-risk cytogenetics. Results showed a statistically significant PFS benefit with ixazomib (median, 23.8 months vs. 18 months; HR = 0.69; P = .019).
Most treatment-emergent adverse events were grade 1 or grade 2. A higher percentage of ixazomib-treated patients experienced grade 3 or higher treatment-emergent adverse events (88% vs. 81%) and treatment-emergent adverse events that resulted in treatment discontinuation (35% vs. 27%). Eight percent of patients assigned ixazomib died during the study, compared with 6% of those assigned placebo.
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Facon T, et al. Abstract MM-347. Presented at: Society of Hematologic Oncology Annual Meeting (virtual meeting); Sept. 9-12, 2020.
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