Scientific publications

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

Oct 20, 2017 | Magazine: Blood

Avet-Loiseau H (1), Bahlis NJ (2), Chng WJ (3), Masszi T (4), Viterbo L (5), Pour L (6), Ganly P (7), Palumbo A (8), Cavo M (9), Langer C (10), Pluta A (11), Nagler A (12), Kumar S (13), Ben-Yehuda D (14), Rajkumar SV (13), San-Miguel J (15), Berg D (16), Lin J (16), van de Velde H (16), Esseltine DL (16), di Bacco A (16), Moreau P (17), Richardson PG (18).


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-Rd.

This pre-planned analysis assessed the efficacy and safety of IRd versus 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 versus placebo-Rd in both high-risk and standard-risk cytogenetics subgroups: in high-risk patients, hazard ratio (HR) was 0.543 (95% confidence interval [CI], 0.321-0.918; p = .021), with median PFS of 21.4 versus 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 versus 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 versus 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 RRMM patients with high-risk and standard-risk cytogenetics, and improves the poor PFS associated with high-risk cytogenetic abnormalities. This trial was registered at as NCT01564537.

CITATION  Blood. 2017 Oct 20. pii: blood-2017-06-791228. doi: 10.1182/blood-2017-06-791228