Real-world outcomes of patients with multiple myeloma who reach third-line therapy: a Canadian report

Martha L Louzada; Donna Reece; Christopher P Venner; Darrell White; Jiandong Su; Michael P Chu; Victor H Jimenez-Zepeda; Arleigh Mccurdy; Kevin Song; Hira Mian; Michael Sebag; Debra Bergstrom; Julie Stakiw; Anthony Reiman; Rami Kotb; Muhammad Aslam; Rayan Kaedbey; Engin Gul; Smriti Sharma; Richard LeBlanc

doi:10.1016/j.bneo.2026.100215

Real-world outcomes of patients with multiple myeloma who reach third-line therapy: a Canadian report

Blood Neoplasia. 2026 Mar 10;3(2):100215. doi: 10.1016/j.bneo.2026.100215. eCollection 2026 May.

Authors

Martha L Louzada¹, Donna Reece^{2

3}, Christopher P Venner⁴, Darrell White⁵, Jiandong Su³, Michael P Chu⁶, Victor H Jimenez-Zepeda⁷, Arleigh Mccurdy⁸, Kevin Song⁴, Hira Mian⁹, Michael Sebag¹⁰, Debra Bergstrom¹¹, Julie Stakiw¹², Anthony Reiman¹³, Rami Kotb¹⁴, Muhammad Aslam¹⁵, Rayan Kaedbey¹⁶, Engin Gul³, Smriti Sharma³, Richard LeBlanc¹⁷

Affiliations

¹ London Regional Cancer Center, London, ON, Canada.
² Princess Margaret Cancer Centre, Toronto, ON, Canada.
³ Canadian Myeloma Research Group, Vaughan, ON, Canada.
⁴ BC Cancer Agency, Vancouver General Hospital, Vancouver, BC, Canada.
⁵ Queen Elizabeth II Health Sciences Centre, Dalhousie University, Halifax, NS, Canada.
⁶ Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada.
⁷ Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB, Canada.
⁸ The Ottawa Hospital, Ottawa, ON, Canada.
⁹ Juravinski Cancer Center, Hamilton, ON, Canada.
¹⁰ Department of Medicine, McGill University, Montreal, QC, Canada.
¹¹ Division of Hematology, Department of Medicine, Memorial University of Newfoundland, St John's, NL, Canada.
¹² Saskatoon Cancer Centre, University of Saskatchewan, Saskatoon, SK, Canada.
¹³ Department of Oncology, Saint John Regional Hospital, Saint John, NB, Canada.
¹⁴ Cancer Care Manitoba, Winnipeg, MB, Canada.
¹⁵ Allan Blair Cancer Centre, Regina, SK, Canada.
¹⁶ Jewish General Hospital, Montreal, Quebec, Canada.
¹⁷ Hematology-Oncology and Cell Therapy University Institute, Hôpital Maisonneuve-Rosemont Research Center, Université de Montréal, Montreal, QC, Canada.

Abstract

Multiple myeloma (MM) remains an incurable cancer and is characterized by a remitting-relapsing pattern. The choice of next line of therapy depends on patient-, disease-, and treatment-related factors. The Canadian Myeloma Research Group database (CMRG-DB) hosts information in ≥10 000 individuals with plasma cell disorders across major Canadian institutions. In this retrospective study, we evaluated therapy choices and outcomes of patients with MM undergoing third-line (3L) therapy using the CMRG-DB platform. All patients with relapsed MM in the CMRG-DB who started 3L therapy between January 2015 and December 2020 were potentially eligible. A total of 1125 patients were included. The most common 3L therapies included immunomodulatory agents (702 [62.4%]), proteasome inhibitors (PIs; 491 [43.6%]), and anti-CD38 monoclonal antibodies (CD38 mAb; 277 [24.6%]). Combinations of daratumumab plus lenalidomide with or without corticosteroid produced the best responses, with a median progression-free survival (mPFS) of 25.6 months (95% confidence interval [CI], 20-35.7). An anti-CD38 mAb plus pomalidomide with or without steroid and other PI-based regimens had a much shorter mPFS, between 6 and 9 months. Adverse prognosticators were high-risk fluorescence in situ hybridization, shorter time from myeloma diagnosis to 3L, triple-class exposure, previous PI exposure, and refractoriness to lenalidomide. The median overall survival was 29.7 months (95% CI, 26.4-32.8). Our findings highlight the role of anti-CD38 mAb combined with lenalidomide for improvement of 3L outcomes. The results of combinations selected for 3L therapy by Canadian hematologists provide information on resource use and benchmark outcomes, which, in turn, will be useful for multiple stakeholders in the rapidly evolving myeloma therapeutic landscape.

© 2026 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.