Fonseca Discusses Rationale for Comparing Daratumumab Use Across Lines of Therapy for Transplant-Ineligible Myeloma

CancerNetwork® spoke with Rafael Fonseca, MD, about the rationale for a simulation using real-world data sets to compare the utility of daratumumab-containing regimens as either frontline or second-line therapy.

At the 63rd American Society of Hematology Annual Meeting & Exposition, CancerNetwork® sat down with Rafael Fonseca, MD, director of Innovation and Transformational Relationships at the Mayo Clinic in Phoenix, Arizona, to talk about an abstract that he presented on the use of daratumumab-containing regimens in patients with transplant-ineligible multiple myeloma. He and his fellow investigators aimed to determine which regimen is most advantageous in the frontline setting, including the MAIA trial regimen (NCT02252172) of daratumumab (Darzalex) plus lenalidomide (Revlimid) and dexamethasone (D-Rd) vs lenalidomide, bortezomib (Velcade), and dexamethasone (RVd) that was originally verified in the SWOG S0777 trial (NCT00644228).


At the 2021 ASH meeting, we were able to present the simulation we did to try to help us understand what the best choice for frontline therapy for patients is who are transplant ineligible. Advanced age patients were not eligible for transplant, what should we use? In all the guidelines, 2 regimens that have been accepted. One of them is the RVd combination. The other one is the combination of D-Rd on what I will refer to going forward as the MAIA2 combination. Both of them are in all the guidelines, and there’s, tradeoffs, but we tried to do a simulation to see if using a real-world data set, we could determine which one might be best.

The reason we did this is because, as we know, patients with myeloma go through various lines of treatments. The big question is if you start with one, and they cross over to another regimen that includes medications that have not been used before, what would you predict will be the best outcome. That was really the drive behind this, and our hypothesis was as follows. When one does a naive comparison between the SWOG study [NCT00644228]3 and the MAIA study [NCT02252172], and especially if one focuses on patients over the age of 65. This is something that has been published in the SWOG study, it appears at first glance that there is superiority with regards to both overall survivals, as well as depth of the response within MAIA regimen versus a SWOG regimen. We wanted to do a little bit more formal modeling behind that and see if we could provide information regarding the best choice for those patients.


Fonesca R, Facon T, Hashim M, et al. First-Line Use of Daratumumab, Lenalidomide, and Dexamethasone Confers Survival Benefit Compared with Second-Line Use of Daratumumab-Based Regimens in Transplant-Ineligible Patients with Multiple Myeloma: Analysis of Different Clinical Scenarios. Presented at the 2021 American Society of Hematology Annual Congress. December 11-14, 2021. Virtual. Abstract 118.