» Articles » PMID: 38136255

Upfront or Deferred Autologous Stem Cell Transplantation for Newly Diagnosed Multiple Myeloma in the Era of Triplet and Quadruplet Induction and Minimal Residual Disease/Risk-Adapted Therapy

Overview
Journal Cancers (Basel)
Publisher MDPI
Specialty Oncology
Date 2023 Dec 23
PMID 38136255
Authors
Affiliations
Soon will be listed here.
Abstract

The standards of care for the initial treatment of patients with newly diagnosed multiple myeloma (NDMM) who are eligible for high-dose melphalan and autologous stem cell transplantation (HDM-ASCT) include highly active triplet and quadruplet regimens based on proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies. These regimens are resulting in improved outcomes and increasingly high rates of minimal residual disease (MRD)-negative responses without HDM-ASCT as part of the upfront therapy. Furthermore, recent randomized studies have shown that, while transplant-based approaches as a frontline therapy result in significantly longer progression-free survival compared to non-transplant approaches, this has not translated into an overall survival benefit. Given these developments, and in the context of the treatment burden of undergoing HDM-ASCT, in addition to the acute toxicities and long-term sequelae of HDM, which are associated with the genotoxicity of melphalan, there is an increasing rationale for considering deferring upfront HDM-ASCT in select transplant-eligible patients and saving it as a treatment option for later salvage therapy. Here, we review the latest clinical trial data on upfront or deferred HDM-ASCT and on the activity of quadruplet induction regimens, including rates of MRD-negative responses, and summarize emerging treatment approaches in the upfront setting such as the use of MRD-directed therapy and alternatives to HDM-ASCT.

Citing Articles

Evolution of frontline treatment for multiple myeloma: clinical investigation of quadruplets containing carfilzomib and anti-CD38 monoclonal antibodies.

Costa L, Gay F, Landgren O, Mateos M, Moreau P, Touzeau C Ann Hematol. 2025; .

PMID: 39774926 DOI: 10.1007/s00277-024-06143-7.


Advances in adoptive cellular immunotherapy and therapeutic breakthroughs in multiple myeloma.

Pu J, Liu T, Sharma A, Jiang L, Wei F, Ren X Exp Hematol Oncol. 2024; 13(1):105.

PMID: 39468695 PMC: 11514856. DOI: 10.1186/s40164-024-00576-6.


Multiple Myeloma: The Role of Autologous Stem Cell Transplantation in the Era of Immunotherapy.

Rocchi S, Zannetti B, Marconi G, Lanza F Cells. 2024; 13(10.

PMID: 38786075 PMC: 11120591. DOI: 10.3390/cells13100853.

References
1.
Anderson K, Auclair D, Adam S, Agarwal A, Anderson M, Avet-Loiseau H . Minimal Residual Disease in Myeloma: Application for Clinical Care and New Drug Registration. Clin Cancer Res. 2021; 27(19):5195-5212. PMC: 9662886. DOI: 10.1158/1078-0432.CCR-21-1059. View

2.
Avet-Loiseau H, Ludwig H, Landgren O, Paiva B, Morris C, Yang H . Minimal Residual Disease Status as a Surrogate Endpoint for Progression-free Survival in Newly Diagnosed Multiple Myeloma Studies: A Meta-analysis. Clin Lymphoma Myeloma Leuk. 2019; 20(1):e30-e37. PMC: 7444731. DOI: 10.1016/j.clml.2019.09.622. View

3.
Voorhees P, Kaufman J, Laubach J, Sborov D, Reeves B, Rodriguez C . Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial. Blood. 2020; 136(8):936-945. PMC: 7441167. DOI: 10.1182/blood.2020005288. View

4.
Moreau P, Attal M, Hulin C, Arnulf B, Belhadj K, Benboubker L . Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study. Lancet. 2019; 394(10192):29-38. DOI: 10.1016/S0140-6736(19)31240-1. View

5.
Dhakal B, Shah N, Kansagra A, Kumar A, Lonial S, Garfall A . ASTCT Clinical Practice Recommendations for Transplantation and Cellular Therapies in Multiple Myeloma. Transplant Cell Ther. 2022; 28(6):284-293. DOI: 10.1016/j.jtct.2022.03.019. View