The benefits of early intervention using lenalidomide for high-risk smoldering multiple myeloma: emerging data and its promising clinical impact

ABSTRACT

Introduction

Multiple myeloma is preceded by the early stages: monoclonal gammopathy of unknown significance (M.G.U.S.) and smoldering myeloma (S.M.M.), which are less genomically complex and where patients are overall healthier with preserved quality of life.

Areas covered

This review focuses on the current evidence in risk stratification and initial therapy for these patients with the goal to delay progression to and/or cure multiple myeloma.

Expert opinion

Advances in the understanding of the factors that contribute to myeloma evolution coupled with new therapeutics that have high efficacy and limited toxicity have revolutionized our approach to early myeloma. Although our current recommendation continues to be to observe S.M.M. outside of clinical trials, the clinical benefit of lenalidomide sets the stage for combinations with immunotherapy, which, in our opinion, will likely lead to regulatory approvals and more widespread treatment of early myeloma.

KEYWORDS:

• Smoldering multiple myeloma
• high-risk smoldering multiple myeloma
• immunotherapy
• lenalidomide-based regimen

Article highlights

• Smoldering multiple myeloma (S.M.M.) is widely heterogeneous and accurate risk stratification is crucial for selecting patients with the highest risk of progression to M.M..

• A widely used risk stratification model, the M.A.Y.O.2018 or 20-2-20 model is simple and can be replicated easily across clinical trials, however, lacks genetic, biologic, and immunologic factors that also affect progression.

• Genetic, biologic, and immunologic risk factors are important in the risk stratification of patients with S.M.M.

• The treatment goals of high-risk S.M.M. are either to cure or at least delay the progression to M.M.. No head-to-head comparison studies of these two strategies exists, to our knowledge.

• High-intensity myeloma-like regimens including high-dose melphalan show promising results. However, reported deaths while on study and concerns for clonal resistance or secondary malignancies require careful consideration for these treatments.

• Lower intensity treatments such as combinations with monoclonal antibodies have excellent safety and tolerability profiles, which are particularly attractive in the S.M.M. population. Ongoing randomized studies are leading the way for a more widespread treatment of S.M.M. with these lower intensity treatment strategies.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Declaration of interests

E Manasanch has received research support from Sanofi, Quest Diagnostics, Novartis, JW Pharma, Merck; consultant fees from Takeda, BMS, GSK, Sanofi, and Adaptive Biotechnologies. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This work was supported in part by The MD Anderson Cancer Center Support Grant (P30 CA016672), the Leukemia and Lymphoma Society Specialized Center of Research (LLS SCOR), the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, the Paula and Rodger Riney Foundation and the University of Texas MD Anderson Moon Shot Program.