Dr Krishnan on Maintenance Approaches in Transplant-Ineligible Multiple Myeloma

Amrita Krishnan, MD, executive medical director, Hematology, City of Hope Orange County; director, the Judy and Bernard Briskin Multiple Myeloma Center; professor, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, discusses maintenance therapy for patients with transplant-ineligible, newly diagnosed multiple myeloma, and how factors such as minimal residual disease (MRD) negativity factor into treatment decision-making.

The phase 3 MAIA trial (NCT02252172) evaluated the efficacy of the triplet regimen of daratumumab (Darzalex), lenalidomide (Revlimid), and dexamethasone (D-Rd) in transplant-ineligible patients with newly diagnosed multiple myeloma. The study enrolled patients with a median age of 73 years (range, 45 to 90 years), with 43.6% of participants aged over 75 years.

Data from the final survival analysis of MAIA, presented at the 2024 EHA Hybrid Congress, demonstrated a median overall survival (OS) of 7.5 years with the D-Rd regimen. This represents a significant 33% reduction in the risk of death compared to the lenalidomide and dexamethasone (Rd) regimen (HR, 0.67; 95% CI, 0.55-0.82; nominal P < 0.0001). Specifically, the median OS was 90.3 months for patients receiving D-Rd compared with 64.1 months for those on the Rd regimen. Importantly, the OS benefit of D-Rd over Rd was consistent across various pre-specified subgroups.

These findings support the continued frontline use of the D-Rd triplet regimen for transplant-ineligible, newly diagnosed multiple myeloma. In clinical practice, many patients in this population continue on daratumumab maintenance therapy even after discontinuing dexamethasone, often maintaining a two-drug regimen until disease progression.

The MAIA trial also showed that MRD negativity can be achieved without the need for autologous stem cell transplantation (ASCT) when using a CD38-targeted therapy backbone, such as daratumumab. However, achieving MRD negativity does not necessarily imply the need to intensify therapy if a patient remains MRD positive while on a triplet regimen.

Additionally, the phase 3 IMROZ trial (NCT03319667), which investigated the combination of isatuximab (Sarclisa) with bortezomib (Velcade), lenalidomide, and dexamethasone (Isa-VRd) in newly diagnosed, transplant-ineligible multiple myeloma, also demonstrated a high rate of MRD negativity. This further suggests that MRD negativity is achievable in transplant-ineligible populations with effective triplet or quadruplet therapy regimens, reinforcing the potential of such treatments to offer significant benefits without the need for ASCT.