Affiliations
- 1Department of Hematology-Oncology, National University Cancer Institute, Singapore, Singapore. mdccwj@nus.edu.sg.
- 2Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore. mdccwj@nus.edu.sg.
- 3Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University Medical School, Emory University, Atlanta, GA, USA.
- 4Perlmutter Cancer Center, NYU Langone Health, New York, NY, USA.
- 5Department of Hematology and Oncology, Nagoya City University Institute of Medical and Pharmaceutical Sciences, Nagoya, Japan.
- 6Hematology Department, University Hospital Hotel Dieu, Nantes, France.
- 7Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
- 8Takeda Development Center Americas, Inc. (TDCA), Lexington, MA, USA.
- 9Hematology and Medical Oncology, Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece.
Abstract
Some cytogenetic abnormalities (CAs) are associated with poorer prognosis in multiple myeloma (MM); proteasome inhibitors appear to benefit patients with high-risk CAs. We evaluated 2247 MM patients from the TOURMALINE-MM1/-MM2/-MM3/-MM4 trials to assess the PFS benefit of ixazomib plus lenalidomide-dexamethasone (Rd) vs placebo-Rd (TOURMALINE-MM1/-MM2) or ixazomib vs placebo (TOURMALINE-MM3/-MM4) in specific high-risk CAs. After a pooled median follow-up of 25.6 months, the hazard ratio (HR) for PFS with ixazomib- vs placebo-based therapy for high-risk patients was 0.74 (95% confidence interval [CI]: 0.59-0.93; median PFS [mPFS] 17.8 vs 13.2 months), and 0.70 (95% CI: 0.62-0.80; mPFS 26.3 vs 17.6 months) for complementary standard-risk patients. The HR for expanded high-risk patients was 0.75 (95% CI: 0.64-0.87; mPFS 18.1 vs 14.1 months), and 0.71 (95% CI: 0.59-0.85; mPFS 36.1 vs 21.4 months) for complementary standard-risk patients. The HR for PFS with ixazomib- vs placebo-based therapy was 0.68 in patients with t(4;14) (95% CI: 0.48-0.96; mPFS 22.4 vs 13.2 months), and 0.77 for patients with amp1q21 (95% CI: 0.63-0.93; mPFS 18.8 vs 14.5 months). A PFS benefit was demonstrated with ixazomib- vs placebo-based therapy regardless of cytogenetic status, with greatest benefit observed in patients with t(4;14) and amp1q21.
PMID: 36631458 DOI: 10.1038/s41408-022-00768-5