Late versus early response and depth of response are associated with improved outcomes in patients with newly diagnosed multiple myeloma enrolled in the TOURMALINE‐MM2 trial

• Type of Material: Article
• Authors: Paul G. Richardson, Dana-Farber Cancer Institute; Thierry Facon, University of Lille; Christopher P. Venner, University of Alberta; Nizar J. Bahlis, University of Calgary; Fritz Offner, UZ Gent; Darrell White, Dalhousie University; Lionel Karlin, Hôpital Lyon Sud; Lotfi Benboubker, CHRU TOURS; Eric Voog, Clinique Victor Hugo; Sung-Soo Yoon, Seoul National University; Kenshi Suzuki, Japan Red Cross; Hirohiko Shibayama, Osaka University; Xiaoquan Zhang, Takeda Development Center Americas; miguel Villarreal, Takeda Development Center Americas; Philip Twumasi-Ankrah, Takeda Development Center Americas; Richard Labotka, Takeda Development Center Americas; Robert M. Rifkin, Rocky Mountain Cancer Centers; Sagar Lonial, Emory University; Shaji K. Kumar, Mayo Clinic, Rochester; S. Vincent Rajkumar, Mayo Clinic, Rochester; Philippe Moreau, Centre Hospitalier Universitaire de nantes
• Language: English
• Date: 2023-08-03
• Publisher: John Wiley and Sons Ltd.
• Publication Version: Final Published Version
• Copyright Statement: © 2023 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): https://doi.org/10.1002/jha2.759
• Title of Journal or Parent Work: eJHaem
• Volume: 4
• Issue: 4
• Start Page: 995
• End Page: 1005
• Grant/Funding Information: Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
• Keywords: response kinetics; multiple myeloma; depth of response; ixazomib
• Research Categories: Health Sciences, Oncology

Abstract

Deeper responses are associated with longer survival in multiple myeloma (MM); however, limited data exist on the impact of response kinetics on outcomes. We investigated progression‐free survival (PFS) and duration of response (DOR) by response depth and in early (best confirmed response 0–4 months; n = 424) versus late responders (best confirmed response >4 months; n = 281). Newly diagnosed patients enrolled in TOURMALINE‐MM2 receiving ixazomib‐lenalidomide‐dexamethasone (IRd) (n = 351) or placebo‐Rd (n = 354) were evaluated post hoc. Deeper responses were associated with longer PFS (complete response [CR] not reached [NR], very good partial response [VGPR] 37.2 months, partial response [PR] 16.4 months) and DOR (CR NR, VGPR 42.6 months, PR 15.4 months). Among patients with a PFS (n = 511) or DOR (n = 484) of ≥6 months who achieved ≥PR, median PFS was prolonged among late versus early responders receiving IRd (59.7 vs. 17.9 months) or placebo‐Rd (56.6 vs. 12.4 months), as was median DOR (IRd, NR vs. 20.9 months; placebo‐Rd, 58.2 vs. 11.7 months). While the treatment paradigm for newly diagnosed MM is treatment to progression, our findings suggest slowness of response to a proteasome inhibitor‐immunomodulatory drug‐steroid combination is not a negative predictor of outcome.