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

Wee-Joo Chng; Sagar Lonial; Gareth J Morgan; Shinsuke Iida; Philippe Moreau; Shaji K Kumar; Philip Twumasi-Ankrah; Miguel Villarreal; Ajeeta B Dash; Alexander Vorog; Xiaoquan Zhang; Kaveri Suryanarayan; Richard Labotka; Meletios A Dimopoulos; S Vincent Rajkumar

doi:10.1038/s41408-022-00768-5

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

Blood Cancer J. 2023 Jan 12;13(1):14. doi: 10.1038/s41408-022-00768-5.

Authors

Wee-Joo Chng^{1

2}, Sagar Lonial³, Gareth J Morgan⁴, Shinsuke Iida⁵, Philippe Moreau⁶, Shaji K Kumar⁷, Philip Twumasi-Ankrah⁸, Miguel Villarreal⁸, Ajeeta B Dash⁸, Alexander Vorog⁸, Xiaoquan Zhang⁸, Kaveri Suryanarayan⁸, Richard Labotka⁸, Meletios A Dimopoulos⁹, S Vincent Rajkumar⁷

Affiliations

¹ Department of Hematology-Oncology, National University Cancer Institute, Singapore, Singapore. mdccwj@nus.edu.sg.
² Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore. mdccwj@nus.edu.sg.
³ Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University Medical School, Emory University, Atlanta, GA, USA.
⁴ Perlmutter Cancer Center, NYU Langone Health, New York, NY, USA.
⁵ Department of Hematology and Oncology, Nagoya City University Institute of Medical and Pharmaceutical Sciences, Nagoya, Japan.
⁶ Hematology Department, University Hospital Hotel Dieu, Nantes, France.
⁷ Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
⁸ Takeda Development Center Americas, Inc. (TDCA), Lexington, MA, USA.
⁹ Hematology 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.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Combined Chemotherapy Protocols / adverse effects
Boron Compounds / adverse effects
Chromosome Aberrations
Dexamethasone / adverse effects
Humans
Lenalidomide / therapeutic use
Multiple Myeloma* / drug therapy
Multiple Myeloma* / genetics

Substances

tourmaline
Lenalidomide
ixazomib
Dexamethasone
Boron Compounds

Grants and funding

P50 CA186781/CA/NCI NIH HHS/United States