Defining High-Risk SMM: Applying IMWG Criteria to Guide Daratumumab Treatment

In an interview with Targeted Oncology, Peter Voorhees, MD, Atrium Health Levine Cancer Institute and Wake Forest University School of Medicine, walks through the criteria used for risk stratification in smoldering multiple myeloma (SMM), specifically the International Myeloma Working Group (IMWG) 20/2/20 criteria, and its application in deciding treatment with the newly FDA-approved subcutaneous daratumumab (Darzalex Faspro).

Watch part 1 and part 2 of Dr Voorhees’ interview.

As Dr Voorhees mentioned in part 2, the definition of high-risk SMM has evolved over time and is subject to change in the future. The current definition of high-risk SMM is determined using IMWG’s 20/2/20 criteria, which assigns a point for each of the following 3 parameters:

• If bone marrow involvement with myeloma is greater than 20%.
• If the M-spike is greater than 2 g per deciliter.
• If the affected/unaffected serum free light-chain ratio is greater than 20.

The total points determine a patient’s risk level for progression to active multiple myeloma:

1. 0 points: low risk.
2. 1 point: intermediate risk.
3. 2 or 3 points: high risk.

While the inclusion criteria for the supporting phase 3 AQUILA trial (NCT03301220) were broader than the IMWG criteria, a subanalysis of patients in the trial who did meet the high-risk criteria per IMWG revealed that daratumumab monotherapy resulted in a more pronounced progression-free survival benefit (HR, 0.36).

The clinical significance of the high-risk classification is substantial, as these patients carry an approximately 50% risk of progression to active disease. Therefore, Dr Voorhees recommends that any patient who fulfills the definition of high-risk SMM based on the IMWG criteria should consult with their provider regarding the risks and benefits of daratumumab monotherapy.

Read the full interview here.