Page 35 - Haematologica Vol. 109 - July 2024

REVIEW ARTICLE
Role of minimal residual disease assessment in multiple myeloma
Raphael E. Szalat,1 Kenneth C. Anderson2 and Nikhil C. Munshi2
1Section of Hematology and Medical Oncology, Boston University School of Medicine and Boston Medical Center and 2Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
Abstract
Multiple myeloma (MM) is a hematologic malignancy characterized by clonal proliferation of plasma cells. MM is a hetero- geneous disease, featured by various molecular subtypes with different outcomes. With the advent of very efficient ther- apies including monoclonal antibodies, bispecific T-cell engagers and chimeric antigen receptor T cells (CAR T cells), most MM patients now have a prolonged survival. However, the disease remains incurable, and a subgroup of high-risk patients continue to have early relapse and short survival. Novel and highly sensitive methods have been developed allowing the detection of minimal residual disease (MRD) during or after treatment. Achievement of MRD negativity is a strong and in- dependent prognostic factor in both prospective randomized clinical trials and in the real-world setting. While MRD as- sessment is now a validated endpoint in clinical trials, its incorporation in clinical practice is not yet established and its potential impact on guiding therapy remains under in-depth evaluation. Here we discuss the different methods available for MRD assessment and the role of MRD evaluation in MM management.
Introduction
Multiple myeloma (MM) is a heterogeneous disease charac- terized by more than 10 distinct molecular subtypes asso- ciated with variable outcomes.1 The therapeutic landscape of MM has dramatically changed over the last five years. The incorporation of monoclonal antibodies, first in the relapse setting, and more recently in front-line treatment in a triplet or quadruplet regimen, the approval of chimeric antigen cell (CAR) T-cell therapy, and the recent approval of bi-specific monoclonal antibodies or T-cell engagers have revolutionized MM treatment and prognosis.2-4 With more than 14 drugs approved by the US Food and Drug Administration (FDA), there are now various treatment op- tions and most MM patients now have prolonged survival.2 However, MM remains incurable and therefore the ability to identify high-risk patients, and to appropriately sequence therapy based on disease characteristics and response to treatment is critical. Along with plasma cell molecular and cytogenetic characteristics, response to treatment is another major prognostic factor, and its assessment is an essential part of patient care. The definition of hemato-
logic response has evolved in the past 20 years with the incorporation of novel highly sensitive methods to allow comparison of treatment strategies in clinical trials. Inter- national consensus criteria defining hematologic response in MM were first established in 1998 and revised in 2016, especially to incorporate the free light chain (FLC) dosage. The original definition of a complete response (CR) only required bone marrow (BM) to have <5% plasma cells, irrespective of their clonal nature, while the 2016 criteria defined CR as negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas, and <5% plasma cells in BM aspirates. Stringent CR was defined as CR plus normal FLC ratio and absence of clonal cells in BM biopsy by immunohistochemistry (κ/λ ratio ≤4:1 or ≥1:2 for κ and λ patients, respectively, after counting ≥100 plasma cells). Overall, achievement of CR is associated with a significantly prolonged period of progression-free survival (PFS) and overall survival (OS).5 However, not all patients achieving CR have a good prognosis as some patients achieving CR unfortunately have early relapse or progression. The concept of minimal residual disease (MRD) which refers to the ability to detect a very small
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Correspondence: R. Szalat raphael.szalat@bmc.org
Received: Accepted: Early view:
November 10, 2023. January 31, 2024. February 8, 2024.
https://doi.org/10.3324/haematol.2023.284662
©2024 Ferrata Storti Foundation Published under a CC BY-NC license