Ixazomib significantly prolongs progression-free survival in high-risk relapsed/refractory myeloma patients
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).
(1) University Cancer Center of Toulouse Institut National de la Sante, Toulouse, France
(2) Southern Alberta Cancer Research Institute, University of Calgary, Calgary, AB, Canada.
(3) National University Cancer Institute, Singapore, Singapore.
(4) St. Istvan, St. Laszlo Hospital, 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
(5) Instituto Portugues de Oncologia do Porto Francisco Gentil, Entidade Publica Empresarial (IPOPFG, EPE), Porto, Portugal.
(6) University Hospital Brno, Brno, Czech Republic.
(7) Department of Haematology, Christchurch Hospital, Christchurch, New Zealand.
(8) Division of Hematology, University of Torino, Azienda Ospedaliero-Universitaria (AOU) S. Giovanni Battista, Torino, Italy.
(9) University of Bologna, Bologna, Italy.
(10) University Hospital of Ulm, Ulm, Germany.
(11) Dept of Hematological Oncology, Oncology Spec. Hospital, Brzozow, Poland.
(12) Hematology Division, Chaim Sheba Medical Center, Tel Hashomer, Israel.
(13) Mayo Clinic, Rochester, MN, United States.
(14) Hadassah Medical Center, Kiryat Hadassah, Jerusalem, Israel.
(15) Clinica Universidad de Navarra, Centro Investigacion Medica Aplicada (CIMA), IDISNA, CIBERONC, Pamplona, Spain.
(16) Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, United States.
(17) University Hospital Hotel Dieu, Nantes, France.
(18) Dana-Farber Cancer Institute, Boston, MA, United States.
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 ClinicalTrials.gov as NCT01564537.
CITATION Blood. 2017 Oct 20. pii: blood-2017-06-791228. doi: 10.1182/blood-2017-06-791228