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Medically reviewed by Dr. Samuel Sarmiento, M.D., MPH on August 23, 2023

This study found ixazomib to be an effective and feasible maintenance therapy for newly diagnosed multiple myeloma patients, regardless of age or frailty status.

Elderly multiple myeloma (MM) patients have reduced survival and quality-of-life (QoL) compared to younger patients due to comorbidities, increased toxicity, and early treatment discontinuation, highlighting the need for more tolerable therapies. In the phase III TOURMALINE-MM4 trial, maintenance therapy with ixazomib, a proteasome inhibitor, was efficacious and had a favorable safety profile. 

A recent analysis of the TOURMALINE-MM4 trial, published in the journal Clinical Lymphoma, Myeloma & Leukemia, analyzed whether the progression-free survival (PFS) benefit of ixazomib in nontransplant newly-diagnosed MM patients exists across all age and frailty status subgroups.

Study Population and Characteristics

In this study, 706 patients were enrolled, 425 in the ixazomib arm and 281 in the placebo arm. Of these patients, 10% were <65 years of age, 52% were 65–74 years of age, and 38% were ≥75 years of age. There were 699 patients with available classification data, including 41% characterized as fit, 35% as intermediate-fit, and 24% categorized as frail. PFS benefit with ixazomib vs. placebo was observed across all age and frailty subgroups. The median follow-up was 21.1 months.

Age-Based Differences in Progression-Free Survival 

In patients aged <65, 69% vs. 79% had progressed or died, with a median PFS of 11 vs. 9.3 months in the ixazomib and placebo arms, respectively. In patients aged 65–74, 52% vs. 71% had progressed or died, with a median PFS of 17.9 vs. 9.3 months with ixazomib vs. placebo. In patients aged ≥75, 53% vs. 67% had progressed or died, with a median PFS of 16.7 vs. 10.2 months with ixazomib vs. placebo.

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Significant Progression-Free Survival Benefit Across Patient Groups

In fit patients, 53% vs. 74% had progressed or died, with a median PFS of 18.6 vs. 8.5 months in the ixazomib and placebo arms, respectively. In intermediate-fit patients, 54% vs. 68% had progressed or died, with a median PFS of 17.6 vs. 10.6 months with ixazomib vs. placebo. In frail patients, 53% vs. 69% had progressed or died, with a median PFS of 15.4 vs. 11.1 months with ixazomib vs. placebo. A time-to-progression benefit was observed with ixazomib across all age and frailty subgroups.

Safety Profiles Examined Across Age and Frailty Subgroups

Safety profiles were generally similar across age and frailty subgroups, with some differences, including numerically higher treatment-emergent adverse event (TEAE) rates with ixazomib vs. placebo. Across the age and frailty subgroups, grade ≥3 and serious TEAE rates were generally higher with ixazomib than placebo and increased with increasing age and decreasing fitness in both arms.

Higher Discontinuation Rate in Frail and Elderly Patients 

Similar proportions of patients aged <65 and 6574 discontinued ixazomib and placebo due to TEAEs, while the rate was higher with ixazomib in patients aged ≥75. Among frailty subgroups, treatment discontinuation rates due to TEAEs were somewhat higher with ixazomib vs. placebo, particularly in frail patients.

Ixazomib’s Positive Impact on Quality of Life

Ixazomib did not negatively impact QoL. Patient-reported QoL scores remained similar between both arms and generally unchanged across age and frailty subgroups during the study.

Source:

Bringhen, S., Pour, L., Benjamin, R., Grosicki, S., Min, C., De Farias, D. L. C., Vorog, A., Labotka, R., Wang, B., Cherepanov, D., Cain, L. E., Manne, S., Rajkumar, S. V., & Dimopoulos, M. A. (2023). Ixazomib versus Placebo as Post-Induction Maintenance therapy in Newly Diagnosed Multiple Myeloma patients: An analysis by age and frailty status of the TOURMALINE-MM4 study. Clinical Lymphoma, Myeloma & Leukemia, 23(7), 491–504. https://doi.org/10.1016/j.clml.2023.03.007