Shaji K. Kumar, MD, Mayo Clinic, Rochester, MN, presents an updated analysis of the phase 3 MAIA study, in which the 3-drug therapy of daratumumab plus lenalidomide and dexamethasone showed a progression-free survival (PFS) and overall survival (OS) benefit vs lenalidomide and dexamethasone in transplant-ineligible patients with newly diagnosed multiple myeloma (MM).

This updated analysis continues to support the frontline use of daratumumab added to lenalidomide and dexamethasone in transplant-ineligible patients with newly diagnosed MM. These results were first presented at the 2022 ASH Annual Meeting & Exposition in New Orleans, LA.

Transcript:

Hi. My name is Shaji Kumar. I'm a hematologist at Mayo Clinic in Rochester, Minnesota. I'm here at the 2022 ASH meeting and we'll be presenting the results of the phase 3 MAIA Study that looked at the combination of daratumumab, lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma who are not eligible to undergo autologous stem cell transplantation.

The updated results of the phase 3 trial have a median follow-up of a little over 5 years at this point in time. The trial had previously been presented and the results had demonstrated that addition of a monoclonal-antibody targeting CD38 like daratumumab after the lenalidomide-dexamethasone can improve not only the progression-free survival, but also the overall survival in patients with newly diagnosed myeloma.

Now with the longer follow-up, we have seen that the results are maintained. The median progression-free survival with the daratumumab and lenalidomide-dexamethasone combination is a little over 5 years, which is one of the longest that we have seen in this patient population. We also have seen significantly higher response rates, particularly the deeper responses like complete response and [molecular residual disease] MRD negativity with the use of daratumumab and [lenalidomide-dexamethasone] compared to lenalidomide and dexamethasone [alone].

In fact, the MRD negativity rate is almost 3-fold, approximately 30% compared to over 12% for the lenalidomide and dexamethasone combination. In addition to the improvement in the progression-free survival, we also continue to see the improvement in overall survival being maintained. While we have not achieved or reached a median overall survival, the 5-year estimates are almost 66% at this point in time, and significantly better than what is observed with [solely] lenalidomide and dexamethasone.

With the longer term follow-up, we really don't see any new safety signals. We do continue to see an increased rate of infections, particularly pneumonia in the daratumumab and [lenalidomide-dexamethasone] combination compared to lenalidomide and dexamethasone. And part of this, we believe, is related to, again, the hypogammaglobulinemia that can be associated with prolonged therapy targeting CD38. Obviously, also we need to make sure that these patients are carefully monitored for infections and early intervention. Adequate therapy for infections is going to be a component of this management strategy.

So, for the newly diagnosed patients who are not eligible to undergo stem cell transplant, we have the 3-drug combination of daratumumab, lenalidomide, dexamethasone, in addition to the [bortezomib]-lenalidomide-dexamethasone that had been used prior. Now, there are no trials comparing these 2 triplets head-to-head, but certainly both remain options for patients with newly diagnosed myeloma who cannot go to a stem cell transplant.

An additional subgroup analysis that is being presented at this meeting has looked at the older patient population as well as the more frail patient population, and the patients with high-risk heterogenetic abnormalities. All of these demonstrate consistent improvement across all these subgroups. And finally, a different presentation looking at patient-reported outcomes also demonstrates no significant worsening of the measurements in the context of getting daratumumab. At the same time, there's a prolongation to the time when these measures actually worsen, possibly associated with disease relapse, and then the 3-drug combination is used. Certainly, the results in total support the continued use of this 3-drug combination for this older patient population.

Source:

Kumar, S J, Moreau P, Bahlis N J et al. Daratumumab Plus Lenalidomide and Dexamethasone (D-Rd) Versus Lenalidomide and Dexamethasone (Rd) Alone in Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma (NDMM). Presented at the ASH Annual Meeting & Exposition; December 10-13, 2022; New Orleans, LA, and virtual. Abstract 4559.