Multiple Myeloma Year in Review Introduction

Dear Colleague,

The year 2020 was an unprecedented year, bringing significant changes in the practice of medicine and knowledge-sharing at scientific forums. National and international meetings, such as the European Hematological Association (EHA) and the American Society of Hematology (ASH), pivoted to facilitate the dissemination of information regarding cutting-edge research and treatment advances in a virtual format. Recognizing the challenges of the virtual format in terms of reach and impact, we are bringing the Year in Review series that seeks to synthesize the presented treatment advances and disseminate them to clinicians in a timely and effective manner to support blood cancer treatment and research.

This edition of Year in Review focuses on multiple myeloma (MM), a plasma-cell malignancy characterized by neoplastic proliferation of plasma cells in bone marrow, resulting in an overabundance of monoclonal paraprotein, extensive skeletal damage, and displacement of other hematopoietic cell lines. Below is a brief review of some of the topics discussed in this issue, with a focus on recent advances, potentially practice-changing developments, and ongoing challenges in MM.

Interim analysis of the phase 3, open-label IKEMA study revealed that treatment of relapsed MM with the monoclonal antibody isatuximab added to carfilzomib and dexamethasone leads to clear improvement in progression-free survival (PFS) with a tolerable safety profile. In addition, retrospective analyses of the ICARIA-MM study, which looked at isatuximab plus pomalidomide and dexamethasone in patients with relapsed/refractory MM (RRMM), were shared. Data from these studies provide insights for clinicians that are integrating isatuximab into treatment regimens following its FDA approval in March 2020 (in combination with pomalidomide and dexamethasone in RRMM patients who have received lenalidomide and a proteasome inhibitor [PI]).

Key results from other immunotherapies that achieved approval in 2020, including belantamab mafodotin-blmf, an immunoconjugate targeting B-cell maturation antigen (BCMA), and selinexor, an oral selective inhibitor of nuclear export (SINE), were shared at EHA and ASH. The DREAMM-2 study evaluated belantamab mafodotin in patients with RRMM. A subgroup analysis of these data revealed that prior treatment does not affect the efficacy and tolerability of belantamab mafodotin. Interim results from the STOMP study showed that a combination of selinexor, pomalidomide, and dexamethasone offers relatively high overall response rates and encouraging PFS for patients with MM who are heavily pre-treated.

Results of the HORIZON study, which evaluated the efficacy and safety of melflufen, a novel peptide-drug conjugate that delivers an alkylating payload into tumor cells, plus dexamethasone, in patients with RRMM refractory to pomalidomide and/or an anti-CD38 monoclonal antibody after failing on immunomodulatory drugs and PIs revealed that melflufen and dexamethasone can stabilize the disease. In addition, updated results from the ANCHOR study were reported, showing encouraging and well-tolerated treatment efficacy in patients with RRMM taking melphalan flufenamide (melflufen) plus dexamethasone and daratumumab or bortezomib. Based on the results of the HORIZON study, the FDA granted a priority review for the evaluation of intravenous melflufen in combination with dexamethasone in patients with RRMM.

Research continues into the role of each therapy class for the treatment of MM. Triple and quadruple therapy combinations for medications already in use and investigational therapies provide promise for effective treatment.

We are pleased to present the highlights of these topics and more!

Carl Landgren, MD
Professor of Medicine,
Chief of Myeloma Program & Experimental Therapeutics Program
Sylvester Comprehensive Cancer Center, University of Miami
Coral Gables, FL

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