KEY TAKEAWAYS
- The phase III trial aimed to determine the final impact of ixa maintenance on OS in transplant-ineligible patients with newly diagnosed MM, following a previous demonstration of improved PFS.
- The result demonstrated that ixa extended cancer-free time in early myeloma, but OS benefit remains to be seen due to evolving treatment options.
A prior study, TOURMALINE-MM4, demonstrated that ixazomib(ixa) improved progression-free survival(PFS) in transplant-ineligible, newly diagnosed multiple myeloma(MM) patients.
In this study, researchers aimed to determine the final impact of ixa maintenance on overall survival(OS) in transplant-ineligible newly diagnosed MM patients, following a previous demonstration of improved PFS.
Patients eligible for the study, as detailed in previously published methods (Dimopoulos, J Clin Oncol 2020), were randomly assigned to receive either single-agent ixa (n=425) or placebo(pbo) maintenance (n=281) for a maximum of twenty-six 28-day cycles or until progression of disease (PD) or unacceptable toxicity.
With a median follow-up of 57 months for ixa and 58 months for pbo, 43% vs. 41% of patients experienced OS events, yielding a median OS of 65 vs. 70 months ((not statistically significant; HR 1.090; 95%CI 0.861–1.381).
No significant differences in median OS were observed for ixa vs. pbo in patients aged ≥75 years (55 vs. 70 months; HR 1.317; 95% CI 0.909–1.909), frail patients (56 vs. 44 months; HR 0.975; 95% CI 0.613–1.549), and those with baseline high-risk cytogenetics ( [del(17p) and/or t(4;14) and/or t(14;16); 37 vs 48 months; HR 1.357; 95% CI 0.799─2.306 ]).
Median PFS2 (PFS on next-line therapy) for ixa vs. pbo was 51 vs. 50 months (non-significant; HR 0.984; 95% CI 0.777–1.246); median time to next therapy was 22 vs. 17 months (not significant; HR 0.881; 95% CI 0.734–1.058).
In both arms, 72% of patients received ≥1 subsequent anti-cancer therapy, including corticosteroids (67 vs. 67%), immunomodulatory drugs (60 vs. 61%), proteasome inhibitors (PI; 34 vs. 36%), and monoclonal antibodies (26 vs. 26%).
The incidence of new primary malignancies (NPMs) in each treatment arm was 3%, with < 1% incidence of hematological NPMs in either arm; no new safety signals were identified.
The result demonstrated that Ixazomib extended cancer-free time in early myeloma, but OS benefit remains unclear due to evolving treatment options.
Clinical Trial: https://clinicaltrials.gov/study/NCT02312258
Dimopoulos MA. Ixazomib maintenance in transplant-ineligible patients with newly diagnosed multiple myeloma: Final overall survival analysis from the TOURMALINE-MM4 study.
