CELMoDs for the treatment of newly diagnosed and HR smoldering MM

The Multiple Myeloma Hub spoke with Paul Richardson, Dana-Farber Cancer Institute, Boston, US. We asked about the emerging role of cereblon E3 ligase modulators (CELMoDs) in newly diagnosed multiple myeloma (NDMM) and high-risk smoldering MM.

During this interview, Richardson discusses the use of CELMoDs, particularly iberdomide, in earlier lines of therapy. Richardson reviews clinical data on activity and tolerability in newly diagnosed patients, including those who are transplant ineligible, as well as in combination with standard therapies. Richardson also explores the potential role of CELMoDs in maintenance strategies, risk-adapted approaches, and in high-risk smoldering MM.

Key learnings

• Iberdomide is being investigated across earlier disease settings, including transplant-eligible and transplant-ineligible NDMM, as well as in high-risk smoldering MM.
• Iberdomide in combination with dexamethasone, with or without daratumumab, has demonstrated clinical activity in NDMM, including in transplant-ineligible patients, as shown in the CC-220-MM-001 (NCT02773030) study.¹
  • Measurable residual disease (MRD) negativity has been observed in early studies combining iberdomide with daratumumab-based regimens.¹
• Iberdomide is also being evaluated in combination with proteasome inhibitors and within transplant-based strategies, with early data showing deepening responses and conversion to MRD negativity in some patients.^2,3
  • As induction therapy prior to transplantation, iberdomide-based regimens have demonstrated clinical activity, with further deepening of responses following transplantation and MRD negativity in a subset of patients.²
  • Iberdomide is being investigated as post-transplantation maintenance, where improvements in response depth and conversion from MRD-positive to MRD-negative status have been observed across dose cohorts.³
• Iberdomide is being evaluated in risk-adapted approaches, including in the DETERMINATION-2 study, which aims to evaluate MRD-guided strategy incorporating isatuximab–iberdomide-based therapy with the potential for deferral of transplantation in selected patients.
• Phase III studies are ongoing to evaluate the role of CELMoDs in earlier lines of therapy, including as part of first-line and maintenance strategies as well as in high-risk smoldering MM.