Smoldering multiple myeloma 40 years later: a story of unintended disease

ABSTRACT

Introduction: Smoldering multiple myeloma (SMM) is a clonal plasma cell (PC) disorder considered a prelude to MM due to its greater malignant potential compared to monoclonal gammopathy of undetermined significance (MGUS). Despite tectonic changes in the SMM landscape that occurred since it was first distinguished four decades ago, SMM continues to represent a complex and controversial entity causing a great deal of diagnostic and management turmoil.

Areas covered: Author addresses increasingly complicated, ambiguous, as well as some overlooked and misjudged aspects of SMM such as the disease identity, relationship to its counterparts, MGUS and overt MM, its niche in the modern classification of monoclonal gammopathies and management. The PubMed search (1980–2020) was conducted and the current NCCN guidelines reviewed in reference to the diagnosis and treatment of smoldering multiple myeloma.

Expert opinion: A plethora of clinical and biological evidence points to SMM as a source of the ongoing and expanding uncertainty of this condition and calls into question its authenticity as a discrete entity. Until comprehensive testing can predict the progression of pre-myeloma conditions with the utmost precision, attempts at preemptive treatments will fail to answer the basic question of who will benefit from the early treatment and who will not.

KEYWORDS:

• Classification
• MGUS
• multiple myeloma
• smoldering

Article highlights

• Smoldering multiple myeloma (SMM) is a clonal plasma cell disorder considered a prelude to MM due to its greater malignant potential compared to monoclonal gammopathy of undetermined significance (MGUS).

• SMM was introduced in 1980 as an indolent variant of MM. It was discerned from typical MM owing to its indistinguishable from MGUS clinical course.

• International Myeloma Working Group (IMWG) redefined SMM as a broad and diverse group of patients exhibiting dissimilar clinical behaviors and variable prognosis. In retrospect, the indolent variant of MM has been disposed of, and a new, ‘unintended’ SMM category endorsed.

• Because of the confounding disease identity, ever-changing risk stratifications and the lack of reliable predictive markers, the management of SMM became a true conundrum with blurred treatment recommendation and burgeoning but impractical clinical trials.

• The reclassification of SMM as a variant of MGUS – in line of the overwhelming pathogenetic, molecular and clinical evidence – could simplify and rectify premalignant PC dyscrasias to make them more understandable and manageable in everyday oncology practice.

Declaration of interest

The authors have no 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.

Reviewer disclosures

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

Additional information

Funding

This paper was not funded.