TY - JOUR
T1 - Ixazomib Versus Placebo as Postinduction Maintenance Therapy in Newly Diagnosed Multiple Myeloma Patients
T2 - An Analysis by Age and Frailty Status of the TOURMALINE-MM4 Study
AU - Bringhen, Sara
AU - Pour, Luděk
AU - Benjamin, Reuben
AU - Grosicki, Sebastian
AU - Min, Chang Ki
AU - C. de Farias, Danielle Leao
AU - Vorog, Alexander
AU - Labotka, Richard J.
AU - Wang, Bingxia
AU - Cherepanov, Dasha
AU - Cain, Lauren E.
AU - Manne, Sudhakar
AU - Rajkumar, S. Vincent
AU - Dimopoulos, Meletios A.
N1 - Publisher Copyright:
© 2023 The Author(s)
PY - 2023/7
Y1 - 2023/7
N2 - Background: The TOURMALINE-MM4 trial demonstrated a significant and clinically meaningful progression-free survival (PFS) benefit with ixazomib versus placebo as postinduction maintenance in nontransplant, newly-diagnosed multiple myeloma patients, with a manageable and well-tolerated toxicity profile. Materials and Methods: In this subgroup analysis, efficacy and safety were assessed by age (< 65, 65-74, and ≥ 75 years) and frailty status (fit, intermediate-fit, and frail). Results: In this analysis, PFS benefit with ixazomib versus placebo was seen across age subgroups, including patients aged < 65 years (hazard ratio [HR], 0.576; 95% confidence interval [CI], 0.299-1.108; P =.095), 65-74 years (HR, 0.615; 95% CI, 0.467-0.810; P <.001), and ≥ 75 years (HR, 0.740; 95% CI, 0.537-1.019; P =.064). PFS benefit was also seen across frailty subgroups, including fit (HR, 0.530; 95% CI, 0.387-0.727; P <.001), intermediate-fit (HR, 0.746; 95% CI, 0.526-1.058; P =.098), and frail (HR, 0.733; 95% CI, 0.481-1.117; P =.147) patients. With ixazomib versus placebo, rates of grade ≥ 3 treatment-emergent adverse events (TEAEs; 28-44% vs. 10-36%), serious TEAEs (15-29% vs. 3-29%), and discontinuation due to TEAEs (7-19% vs. 5-11%) were higher or similar across age and frailty subgroups, and generally somewhat higher in older age groups and intermediate-fit/frail patients in both arms. Treatment with ixazomib versus placebo did not adversely affect patient-reported quality-of-life scores across age and frailty status subgroups. Conclusion: Ixazomib is a feasible and effective maintenance option for prolonging PFS across this heterogeneous patient population.
AB - Background: The TOURMALINE-MM4 trial demonstrated a significant and clinically meaningful progression-free survival (PFS) benefit with ixazomib versus placebo as postinduction maintenance in nontransplant, newly-diagnosed multiple myeloma patients, with a manageable and well-tolerated toxicity profile. Materials and Methods: In this subgroup analysis, efficacy and safety were assessed by age (< 65, 65-74, and ≥ 75 years) and frailty status (fit, intermediate-fit, and frail). Results: In this analysis, PFS benefit with ixazomib versus placebo was seen across age subgroups, including patients aged < 65 years (hazard ratio [HR], 0.576; 95% confidence interval [CI], 0.299-1.108; P =.095), 65-74 years (HR, 0.615; 95% CI, 0.467-0.810; P <.001), and ≥ 75 years (HR, 0.740; 95% CI, 0.537-1.019; P =.064). PFS benefit was also seen across frailty subgroups, including fit (HR, 0.530; 95% CI, 0.387-0.727; P <.001), intermediate-fit (HR, 0.746; 95% CI, 0.526-1.058; P =.098), and frail (HR, 0.733; 95% CI, 0.481-1.117; P =.147) patients. With ixazomib versus placebo, rates of grade ≥ 3 treatment-emergent adverse events (TEAEs; 28-44% vs. 10-36%), serious TEAEs (15-29% vs. 3-29%), and discontinuation due to TEAEs (7-19% vs. 5-11%) were higher or similar across age and frailty subgroups, and generally somewhat higher in older age groups and intermediate-fit/frail patients in both arms. Treatment with ixazomib versus placebo did not adversely affect patient-reported quality-of-life scores across age and frailty status subgroups. Conclusion: Ixazomib is a feasible and effective maintenance option for prolonging PFS across this heterogeneous patient population.
KW - Frailty
KW - Ixazomib
KW - Maintenance therapy
KW - Multiple myeloma
KW - Newly-diagnosed
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U2 - 10.1016/j.clml.2023.03.007
DO - 10.1016/j.clml.2023.03.007
M3 - Article
C2 - 37149398
AN - SCOPUS:85158824362
SN - 2152-2650
VL - 23
SP - 491
EP - 504
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
IS - 7
ER -