Fonseca Talks Future Research Comparing First- Vs Second-Line Daratumumab for Transplant-Ineligible Myeloma

CancerNetwork® spoke with Rafael Fonseca, MD, about future efforts to compare use of daratumumab-containing regimens as either frontline or second-line therapy in patients with multiple myeloma that are transplant ineligible.

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, who presented data from a simulation that demonstrated superiority of daratumumab-containing regimens as front- vs second-line therapy in patients with multiple myeloma who are not eligible for transplant. He added that these data will be crucial given the fact that randomized data sets comparing available agents in the frontline setting will take a long time to produce.


From what I understand, there are some trials that are being considered and planned that will address direct comparison of these regiments and in subsets of patients. Of course, like everyone else, we should be very interested in hearing about them. Those trials will take a significant amount of time.

For the patient who’s diagnosed tomorrow, we have the 2 options of using something like RVd [lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone] or going with the MAIA trial [NCT02252172] combination [of daratumumab (Darzalex) plus lenalidomide and dexamethasone (D-Rd)]. I personally have changed my practice. Most of my patients I treat with D-Rd.

Now, another logical question would be [around what to] do with different patients who have high-risk disease. We did not address this in the study, but this is how I deal with this. We know historically that proteasome inhibitors [PIs], including bortezomib, which is part of RVd, appear to help patients with high-risk disease, so why not use it there? Well, one of the challenges is that we derived that information from a time when we were comparing single-agent PIs or PIs with dexamethasone versus lenalidomide and dexamethasone. It’s very clear that IMIDs [immunomodulatory drugs] plus dexamethasone are insufficient at large for high-risk patients.

Just recently, there was a meta-analysis that looked at daratumumab in high-risk disease and there’s also some data for isatuximab [Sarclisa]. We also have data compelling for selinexor [Xpovio] in patients with deletion 17. The question is, is it truly that PIs are better for high-risk disease, or is it just that IMIDs are bad for high-risk disease as a single agent. That’s one of the possibilities. The second part of that question is that high-risk disease is less common in patients of advancing age who tend to be more standard risk and are particularly enriched for the hyperdiploid variant?


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.