Timing treatment for smoldering myeloma: is earlier better?

INTRODUCTION: In 2014, the International Myeloma Working Group determined that patients with ultra-high-risk smoldering multiple myeloma (SMM) should be considered for treatment as per patients with symptomatic multiple myeloma (MM), despite not having CRAB (hyperCalcemia, Renal insufficiency, Anemia, Bone disease) symptoms. Current research is elucidating whether patients with high-risk, and even intermediate-risk, SMM could benefit from early therapeutic strategies aimed at delaying progression to active MM and prolonging survival. Areas covered: The authors conducted a systematic literature search using PubMed to identify a series of patients with SMM in which prognostic and predictive factors for progression were investigated, plus the main clinical trials in SMM. Additionally, a search of active clinical trials in SMM was conducted at ClinicalTrials.gov. Expert opinion: Patients with high-risk SMM can benefit from active treatment strategies, which may prolong survival and, perhaps, provide a possible path to cure. Enabled by the limited toxicity of new drugs investigated in MM, this approach, together with consolidation with autologous transplantation, is under investigation by American and European groups. In patients with high-risk SMM who are not candidates for transplantation, combinations of oral drugs may prolong time to progression. In the near future, these approaches may be endorsed by results of ongoing clinical trials.