A pooled analysis of outcomes according to cytogenetic abnormalities in patients receiving ixazomib- vs placebo-based therapy for multiple myeloma

• Type of Material: Article
• Authors: Wee-Joo Chng, National University Cancer Institute; Sagar Lonial, Emory University; Gareth J Morgan, NYU Langone Health; Shinsuke Iida, Nagoya City University; Philippe Moreau, University Hospital Hotel Dieu; Shaji K Kumar, Mayo Clinic, Rochester; Philip Twumasi-Ankrah, Takeda Development Center Americas, Inc. (TDCA); Miguel Villarreal, Takeda Development Center Americas, Inc. (TDCA); Ajeeta B Dash, Takeda Development Center Americas, Inc. (TDCA); Alexander Vorog, Takeda Development Center Americas, Inc. (TDCA); Xiaoquan Zhang, Takeda Development Center Americas, Inc. (TDCA); Kaveri Suryanarayan, Takeda Development Center Americas, Inc. (TDCA); Richard Labotka, Takeda Development Center Americas, Inc. (TDCA); Meletios A Dimopoulos, National and Kapodistrian University of Athens; Vincent S Rajkumar, Mayo Clinic, Rochester
• Language: English
• Date: 2023-12-01
• Publisher: Springer Nature Limited
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2023
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41408-022-00768-5
• Title of Journal or Parent Work: Blood Cancer Journal
• Volume: 13
• Issue: 1
• Start Page: 14
• End Page: 14
• Grant/Funding Information: These studies were funded by Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
• Keywords: Multiple Myeloma; Humans; Chromosome Aberrations; Lenalidomide; Boron Compounds; Antineoplastic Combined Chemotherapy Protocols; Dexamethasone
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Oncology

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.