Ixazomib significantly prolongs progression-free survival in high-risk relapsed/refractory myeloma patients

Hervé Avet-Loiseau, Nizar J. Bahlis, Wee Joo Chng, Tamas Masszi, Luisa Viterbo, Ludek Pour, Peter Ganly, Antonio Palumbo, Michele Cavo, Christian Langer, Andrzej Pluta, Arnon Nagler, Shaji Kumar, Dina Ben-Yehuda, S. Vincent Rajkumar, Jesus San-Miguel, Deborah Berg, Jianchang Lin, Helgi Van De Velde, Dixie Lee EsseltineAlessandra di Bacco, Philippe Moreau, Paul G. Richardson

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38 Citations (Scopus)

Abstract

Certain cytogenetic abnormalities are known to adversely impact outcomes in patients with multiple myeloma (MM). The phase 3 TOURMALINE-MM1 study demonstrated a significant improvement in progression-free survival (PFS) with ixazomib-lenalidomide-dexamethasone (IRd) compared with placebo-lenalidomide-dexamethasone (placebo-Rd). This preplanned analysis assessed the efficacy and safety of IRd vs placebo-Rd according to cytogenetic risk, as assessed using fluorescence in situ hybridization. High-risk cytogenetic abnormalities were defined as del(17p), t(4;14), and/or t(14;16); additionally, patients were assessed for 1q21 amplification. Of 722 randomized patients, 552 had cytogenetic results; 137 (25%) had high-risk cytogenetic abnormalities and 172 (32%) had 1q21 amplification alone. PFS was improved with IRd vs placebo-Rd in both high-risk and standard-risk cytogenetics subgroups: in high-risk patients, the hazard ratio (HR) was 0.543 (95% confidence interval [CI], 0.321-0.918; P = .021), with median PFS of 21.4 vs 9.7 months; in standard-risk patients, HR was 0.640 (95% CI, 0.462-0.888; P = .007), with median PFS of 20.6 vs 15.6 months. This PFS benefit was consistent across subgroups with individual high-risk cytogenetic abnormalities, including patients with del(17p) (HR, 0.596; 95% CI, 0.286-1.243). PFS was also longer with IRd vs placebo-Rd in patients with 1q21 amplification (HR, 0.781; 95% CI, 0.492-1.240), and in the “expanded high-risk” group, defined as those with high-risk cytogenetic abnormalities and/or 1q21 amplification (HR, 0.664; 95% CI, 0.474-0.928). IRd demonstrated substantial benefit compared with placebo-Rd in relapsed and/or refractory MM (RRMM) patients with high-risk and standard-risk cytogenetics, and improves the poor PFS associated with high-risk cytogenetic abnormalities.

Original languageEnglish
Pages (from-to)2610-2618
Number of pages9
JournalBlood
Volume130
Issue number24
DOIs
Publication statusPublished - Dec 14 2017

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Avet-Loiseau, H., Bahlis, N. J., Chng, W. J., Masszi, T., Viterbo, L., Pour, L., Ganly, P., Palumbo, A., Cavo, M., Langer, C., Pluta, A., Nagler, A., Kumar, S., Ben-Yehuda, D., Rajkumar, S. V., San-Miguel, J., Berg, D., Lin, J., Van De Velde, H., ... Richardson, P. G. (2017). Ixazomib significantly prolongs progression-free survival in high-risk relapsed/refractory myeloma patients. Blood, 130(24), 2610-2618. https://doi.org/10.1182/blood-2017-06-791228