Dr Landgren on the Management of Newly Diagnosed Multiple Myeloma Treatment

C. Ola Landgren, MD, PhD, professor, medicine, Department of Medicine, chief, Division of Myeloma, Department of Medicine; co-leader, Translational and Clinical Oncology Program; Paul J. DiMare Endowed Chair in Immunotherapy, director, Sylvester Myeloma Institute, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, discusses standard treatment regimens for patients with newly diagnosed multiple myeloma, and highlights the advantages of utilizing a quadruplet regimen rather than a triplet or doublet in this setting.

Landgren begins by stating that he frequently uses quadruplet combinations for newly diagnosed patients in his own practice, though he also uses triplet combinations. These choices are guided by FDA approvals and the National Comprehensive Cancer Network (NCCN) Guidelines, he states.

One common quadruplet regimen is daratumumab (Darzalex) plus carfilzomib, lenalidomide (Revlimid), and dexamethasone (Dara-KRd), which is recommended by the NCCN Guidelines for use in transplant-eligible patients, Landgren explains. Notably, this regimen was developed in the phase 2 MANHATTAN trial (NCT03500445), he adds. Additionally, the phase 3 MAIA (NCT02252172) study regimen consisting of daratumumab, lenalidomide, and dexamethasone, is often selected for newly diagnosed patients.

The combination of daratumumab, bortezomib (Velcade), lenalidomide, and dexamethasone (VRd) is another viable option for certain patients, and can be adjusted as needed, Landgren adds. For instance, lenalidomide is typically replaced with cyclophosphamide for patients with renal failure, he says.

Quadruplet regimens offer significant advantages over those with fewer agents, he continues. Data presented at the 2024 ASCO Annual Meeting demonstrated that adding a fourth drug to these regimens bolsters its efficacy, Landgren notes. He explains that this approach increases the rate and depth of minimal residual disease (MRD) negativity from a threshold of 10-5, which meets current MRD negativity guidelines, to 10^-6. These deeper responses are associated with prolonged progression-free survival, Landgren concludes.