Advancements in the Treatment of High-Risk Smoldering Myeloma: News from ASH 2024

Smoldering multiple myeloma (SMM) is a precursor to symptomatic multiple myeloma (MM), characterized by its asymptomatic yet progressive nature and significant risk of progression. The management of SMM has evolved considerably in recent years with the introduction of targeted therapies. While the traditional "watch and wait" strategy remains the standard approach for low-risk cases, early treatment for high-risk SMM has become increasingly favored, backed by clinical trials highlighting its ability to delay the progression to MM and reduce related complications. The AQUILA trial, a phase III multicenter study, evaluated subcutaneous daratumumab as a monotherapy for high-risk SMM compared to active monitoring. With 390 participants, the trial demonstrated a significant reduction in the progression to MM or death, with a 51% risk reduction and favorable safety results. By validating daratumumab monotherapy as an effective and safe early intervention for high-risk SMM, the AQUILA trial underscores a pivotal shift in disease management. These findings complement existing evidence from trials, such as QUIREDEX and E3A06, emphasizing the value of proactive treatment strategies. AQUILA also highlights the need for continued research into dynamic risk stratification, biomarker-driven approaches, and innovative therapies, paving the way for precision medicine in SMM care. PEER REVIEWED ARTICLE Peer reviewers: Dr Thomas Lehmann, Cantonal Hospital St. Gallen, St. Gallen, Switzerland One anonymous peer reviewer Received on December 15, 2024; accepted after peer review on December 30, 2024; published online on December 31, 2024.