Clinical implications of loss of bone marrow minimal residual disease negativity in multiple myeloma.

Abstract

Multiple myeloma (MM) patients frequently attain a bone marrow (BM) minimal residual disease (MRD) negativity status in response to treatment. We identified 568 patients who achieved BM MRD negativity following autologous stem cell transplantation (ASCT) and maintenance combination therapy with an immunomodulatory agent and a proteasome inhibitor. BM MRD was evaluated by next-generation flow cytometry (sensitivity of 10-5 cells) at 3- to 6-month intervals. With a median follow-up of 9.9 years from diagnosis (range, 0.4-30.9), 61% of patients maintained MRD negativity, whereas 39% experienced MRD conversion at a median of 6.3 years (range, 1.4-25). The highest risk of MRD conversion occurred within the first 5 years after treatment and was observed more often in patients with abnormal metaphase cytogenetic abnormalities (95% vs 84%; P = .001). MRD conversion was associated with a high risk of relapse and preceded it by a median of 1.0 years (range, 0-4.9). However, 27% of MRD conversion-positive patients had not yet experienced a clinical relapse, with a median follow-up of 9.3 years (range, 2.2-21.2). Landmark analyses using time from ASCT revealed patients with MRD conversion during the first 3 years had an inferior overall and progression-free survival compared with patients with sustained MRD negativity. MRD conversion correctly predicted relapse in 70%, demonstrating the utility of serial BM MRD assessment to complement standard laboratory and imaging to make informed salvage therapy decisions.

• Authors: Meera Mohan, Samantha Kendrick, Aniko Szabo, Naveen Yarlagadda, Dinesh Atwal, Yadav Pandey, Arya Roy, Richa Parikh, James Lopez, Sharmilan Thanendrarajan, Carolina Schinke, Daisy Alapat, Jeffrey Sawyer, Erming Tian, Guido Tricot, Frits van Rhee, Maurizio Zangari
• Journal: Blood advances (Blood Adv) Vol. 6 Issue 3 Pg. 808-817 (02 08 2022) ISSN: 2473-9537 [Electronic] United States
• PMID: 34807986 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 by The American Society of Hematology. 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.

Topics

• Bone Marrow
• Hematopoietic Stem Cell Transplantation
• Humans
• Multiple Myeloma (drug therapy, therapy)
• Neoplasm Recurrence, Local
• Neoplasm, Residual (diagnosis)
• Transplantation, Autologous
• Treatment Outcome