High-risk smoldering myeloma - a case for early intervention?

Smoldering myeloma (SMM) is an asymptomatic precursor condition of multiple myeloma (MM) with a prevalence of about 0.5% in those aged >40 years age. While the current standard of care is active surveillance, there is a growing interest to determine the effectiveness of early intervention in this condition. This review discusses the contemporary trials focussed on treating SMM and the case for additional data in this space.

It is imperative to note that the risk stratification for SMM has constantly evolved over time. A proportion of patients with SLiM-CRAB [≥60% bone marrow plasma cells (BMPCs), free light chain ratio (sFLC-ratio) ≥100, and >1 MRI-defined ≥5 mm focal bony lesion, hypercalcemia, renal insufficiency, anaemia, lytic bone lesions], who were classified as high-risk-SMM in the past, have now been classified as MM, based on the IMWG-2014 diagnostic criteria. Current research on SMM risk stratification is focussed on developing models based on longitudinal trends, rather than single-point measures. Earlier trials were studying disease control strategy, working towards delaying disease progression. As the results were promising, currently, there are more trials utilizing intensive treatment approaches aiming at cure to eradicate disease clone (achieving sustained MRD negativity). Further ongoing trials, are attempting to refine disease control strategy and utilize immunotherapies.

We need more high-quality evidence in post-SLiM-CRAB SMM cohort to better identify the subset of patients most likely to benefit from early intervention. Treatment approaches should be refined considering patient preferences and maintaining quality of life (QoL).