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

Hervé Avet-Loiseau, Nizar J. Bahlis, Wee Joo Chng, T. 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

Research output: Article

29 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

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Refractory materials
Disease-Free Survival
Chromosome Aberrations
Placebos
Hazards
Cytogenetics
Amplification
Confidence Intervals
Multiple Myeloma
ixazomib
Dexamethasone
Fluorescence In Situ Hybridization
Fluorescence
Safety

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Avet-Loiseau, H., Bahlis, N. J., Chng, W. J., Masszi, T., Viterbo, L., Pour, L., ... 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

Ixazomib significantly prolongs progression-free survival in high-risk relapsed/refractory myeloma patients. / Avet-Loiseau, Hervé; Bahlis, Nizar J.; Chng, Wee Joo; Masszi, T.; Viterbo, Luisa; Pour, Ludek; Ganly, Peter; Palumbo, Antonio; Cavo, Michele; Langer, Christian; Pluta, Andrzej; Nagler, Arnon; Kumar, Shaji; Ben-Yehuda, Dina; Rajkumar, S. Vincent; San-Miguel, Jesus; Berg, Deborah; Lin, Jianchang; Van De Velde, Helgi; Esseltine, Dixie Lee; di Bacco, Alessandra; Moreau, Philippe; Richardson, Paul G.

In: Blood, Vol. 130, No. 24, 14.12.2017, p. 2610-2618.

Research output: Article

Avet-Loiseau, H, Bahlis, NJ, Chng, WJ, Masszi, T, Viterbo, L, Pour, L, Ganly, P, Palumbo, A, Cavo, M, Langer, C, Pluta, A, Nagler, A, Kumar, S, Ben-Yehuda, D, Rajkumar, SV, San-Miguel, J, Berg, D, Lin, J, Van De Velde, H, Esseltine, DL, di Bacco, A, Moreau, P & Richardson, PG 2017, 'Ixazomib significantly prolongs progression-free survival in high-risk relapsed/refractory myeloma patients', Blood, vol. 130, no. 24, pp. 2610-2618. https://doi.org/10.1182/blood-2017-06-791228
Avet-Loiseau, Hervé ; Bahlis, Nizar J. ; Chng, Wee Joo ; Masszi, T. ; Viterbo, Luisa ; Pour, Ludek ; Ganly, Peter ; Palumbo, Antonio ; Cavo, Michele ; Langer, Christian ; Pluta, Andrzej ; Nagler, Arnon ; Kumar, Shaji ; Ben-Yehuda, Dina ; Rajkumar, S. Vincent ; San-Miguel, Jesus ; Berg, Deborah ; Lin, Jianchang ; Van De Velde, Helgi ; Esseltine, Dixie Lee ; di Bacco, Alessandra ; Moreau, Philippe ; Richardson, Paul G. / Ixazomib significantly prolongs progression-free survival in high-risk relapsed/refractory myeloma patients. In: Blood. 2017 ; Vol. 130, No. 24. pp. 2610-2618.
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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.",
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T1 - Ixazomib significantly prolongs progression-free survival in high-risk relapsed/refractory myeloma patients

AU - Avet-Loiseau, Hervé

AU - Bahlis, Nizar J.

AU - Chng, Wee Joo

AU - Masszi, T.

AU - Viterbo, Luisa

AU - Pour, Ludek

AU - Ganly, Peter

AU - Palumbo, Antonio

AU - Cavo, Michele

AU - Langer, Christian

AU - Pluta, Andrzej

AU - Nagler, Arnon

AU - Kumar, Shaji

AU - Ben-Yehuda, Dina

AU - Rajkumar, S. Vincent

AU - San-Miguel, Jesus

AU - Berg, Deborah

AU - Lin, Jianchang

AU - Van De Velde, Helgi

AU - Esseltine, Dixie Lee

AU - di Bacco, Alessandra

AU - Moreau, Philippe

AU - Richardson, Paul G.

PY - 2017/12/14

Y1 - 2017/12/14

N2 - 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.

AB - 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.

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