Management of Relapsed–Refractory Multiple Myeloma in the Era of Advanced Therapies: Evidence-Based Recommendations for Routine Clinical Practice

Abstract

Multiple myeloma (MM) is the second most common hematologic malignancy in adults worldwide. Over the past few years, major therapeutic advances have improved progression-free and overall survival, as well as quality of life. Despite this recent progress, MM remains incurable in the vast majority of cases. Patients eventually relapse and become refractory to multiple drug classes, making long-term management challenging. In this review, we will focus on the treatment paradigm of relapsed/refractory MM (RRMM) in the era of advanced therapies emphasizing the available novel modalities that have recently been incorporated into routine practice, such as chimeric antigen receptor T-cell therapy, bispecific antibodies, and other promising approaches. We will also discuss major factors that influence the selection of appropriate drug combinations or cellular therapies, such as relapse characteristics, and other disease and patient related parameters. Our goal is to provide insight into the currently available and experimental therapies for RRMM in an effort to guide the therapeutic decision-making process.

An Assessment of the Effectiveness and Safety of Chimeric Antigen Receptor T-Cell Therapy in Multiple Myeloma Patients with Relapsed or Refractory Disease: A Systematic Review and Meta-Analysis

“…Nevertheless, MM remains an incurable hematological malignancy, marked by multiple remission stages and subsequent relapses throughout its clinical course. This is attributed to its intra-, spatial-, and temporal heterogeneity and the ongoing clonal evolution at each stage, conferring MM with high-risk characteristics and resistance to standard treatments [9,10].…”

Impact of Extraosseous Extramedullary Disease on Outcomes of Patients with Relapsed-Refractory Multiple Myeloma receiving Standard-of-Care Chimeric Antigen Receptor T-Cell Therapy

“…The recent introduction of novel agents has radically changed the treatment paradigm of RRMM [5]. Idecabtagene vicleucel (idecel) was the first chimeric antigen receptor (CAR) T-cell therapy product approved in March 2021 by the United States (US) Food and Drug Administration (FDA) for the treatment of RRMM after four or more prior lines of therapy, including a proteasome inhibitor, immunomodulator and anti-CD38 monoclonal antibody based on the results of the pivotal phase I/II KarMMa-1 trial [6].…”

Current Novel Targeted Therapeutic Strategies in Multiple Myeloma

“…Over the past decades, robust preclinical and clinical research has led to the development of novel therapies that have significantly evolved the treatment landscape of MM [3].…”

“…Over the past decades, robust preclinical and clinical research has led to the development of novel therapies that have significantly evolved the treatment landscape of MM [ 3 ]. The introduction of these agents into clinical practice has led to prolonged progression-free survival (PFS) and improved overall survival of patients with a reduced treatment toxicity profile [ 4 ].…”