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.
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.