Understanding High-Risk Smoldering Multiple Myeloma

In an interview with Targeted Oncology, Paula Rodriguez Otero, MD, PhD, consultant and deputy professor at the University of Navarra, discusses the current treatment landscape of smoldering multiple myeloma (SMM).

High-risk SMM is a precancerous condition, a precursor to active multiple myeloma. It's a significant area of research because there's currently no consensus on whether to treat it or not.

A diagnosis of high-risk SMM means a patient has a high chance of their condition progressing to active multiple myeloma, which is defined by the presence of any of the CRAB criteria (Calcium, Renal, Anemia, Bone lesions) or SLiM criteria (Sixty, Light chain, Myeloma-defining event). Using current diagnostic criteria, physicians can identify a group of patients with at least a 50% chance of progressing to active disease within 2 years.

The question of treating SMM has been explored in several key studies. Here are three of the most significant:

• Spanish Myeloma Group Study: This was one of the first studies to show that early treatment could delay progression to multiple myeloma and improve overall survival. The study compared the drug lenalidomide (Revlimid) against observation alone and found that 2 years of treatment with lenalidomide was effective in delaying progression and extending patients' lives.
• ECOG-ACRIN Study: This study confirmed the findings of the Spanish Myeloma Group, showing similar positive outcomes.
• AQUILA Study: This phase 3 randomized study compared the drug daratumumab (Darzalex) with observation. It demonstrated that a fixed duration of treatment with daratumumab could delay progression to multiple myeloma and improve overall survival.

Based on these studies, we now know that treating patients with high-risk SMM can delay or even prevent their condition from progressing to active multiple myeloma. With the development of more potent therapies, such as CAR T-cell therapy and bispecific antibodies, ongoing studies are exploring how these treatments could be used in patients with high-risk SMM.

Read the full interview with Dr Rodriguez Otero here.