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. This trial was registered at www.clinicaltrials.gov as #NCT01564537.

3rd Department of Internal Medicine Semmelweis University Budapest Hungary

Clínica Universidad de Navarra Centro Investigación Médica Aplicada Pamplona Spain

Dana Farber Cancer Institute Boston MA

Department of Haematology Christchurch Hospital Christchurch New Zealand

Department of Hematological Oncology Oncology Specialist Hospital Brzozow Poland

Department of Hematology Oncology National University Cancer Institute Singapore

Department of Internal Medicine 3 University Hospital of Ulm Ulm Germany

Department of Internal Medicine Hematology and Oncology University Hospital Brno Brno Czech Republic

Division of Hematology University of Torino Azienda Ospedaliero Universitaria S Giovanni Battista Torino Italy

Hadassah Medical Center Kiryat Hadassah Jerusalem Israel

Hematology Department University Hospital Hôtel Dieu Nantes France; and

Hematology Division Chaim Sheba Medical Center Tel Hashomer Israel

Instituto Português de Oncologia do Porto Francisco Gentil Entidade Pública Empresarial Porto Portugal

Laboratory for Genomics in Myeloma University Cancer Center of Toulouse Institut National de la Santé Toulouse France

Mayo Clinic Rochester MN

Millennium Pharmaceuticals Inc a wholly owned subsidiary of Takeda Pharmaceutical Company Limited Cambridge MA

Seràgnoli Institute of Hematology University of Bologna Bologna Italy

Southern Alberta Cancer Research Institute University of Calgary Calgary AB Canada

St István St László Hospital Budapest Hungary

References provided by Crossref.org

Survival benefit of ixazomib, lenalidomide and dexamethasone (IRD) over lenalidomide and dexamethasone (Rd) in relapsed and refractory multiple myeloma patients in routine clinical practice

Ixazomib-Thalidomide-Dexamethasone for induction therapy followed by Ixazomib maintenance treatment in patients with relapsed/refractory multiple myeloma

Impact of acquired del(17p) in multiple myeloma

See more in PubMed

ClinicalTrials.gov
NCT01564537, NCT01564537