The quadruple therapy of daratumumab, carfilzomib, lenalidomide, and dexamethasone was well tolerated in patients with smoldering multiple myeloma (MM), with similar toxicities as those observed in active MM. Furthermore, many patients were still in deep response at 2 years. Long-term follow-up will provide insights on whether some of these patients can be cured through this regimen.

“Smoldering MM is a so-called precursor condition, and patients with this condition have a high risk to progress to active MM,” explained Dr. Shaji Kumar (Mayo Clinic) during a presentation at the 2022 annual meeting of the American Society of Hematology. The phase 2 ASCENT trial was designed to assess whether an intense, limited duration, quadruple therapy can result in long-term responses or cure patients with smoldering MM and high-risk disease (N=87).1 An induction regimen of six 4-week cycles with daratumumab, carfilzomib, lenalidomide, and dexamethasone was followed by six 4-week cycles of consolidation therapy and 12 4-week cycles of maintenance therapy with lenalidomide and daratumumab. The primary endpoint was the rate of confirmed stringent complete response (sCR).

The sCR rate was 38%, the CR rate was 26%, and the very good partial response rate was 30%. In addition, 84% of participants achieved marrow MRD-negativity (10-5). The progression-free survival rate at 3 years was 89.9%.

In 81% of participants, a treatment-emergent adverse event (AE) of any grade was observed. Also, 18% of participants experienced a grade 3 hematologic toxicity, wheraes 51% had a non-hematologic toxicity. Decreased neutrophil count, hypertension, and pneumonia were the most common grade 3 AEs. Four deaths were reported, including two due to COVID-19, one because of an RSV infection, and one due to disease progression.

“After 2 years, many patients that were included in this study are still in deep response,” said Dr. Kumar. “Are we able to actually cure some of these patients? The answer to that question has to come from long-term follow-up.”

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