Dr Ola Landgren Outlines High MRD Negativity Rates in Daratumumab Combinations

In the frontline setting, daratumumab added to backbone combination therapies has resulted in high rates of minimal residual disease (MRD) negativity, said Ola Landgren, MD, PhD, professor of medicine and chief of the Myeloma Program at the University of Miami, and leader of the Experimental Therapeutics Program at Sylvester Comprehensive Cancer Center.

Transcript

What are the rates of minimal residual disease for a 4-drug combination with daratumumab compared with the 3-drug combinations without daratumumab?

The role of MRD detection in relation to daratumumab was initially published back in 2016. And this is in the relapse patients. This is from the POLLUX study showing 25% MRD negativity in 1 to 3 prior lines. Now with daratumumab coming up front, people were expecting to see higher rates of MRD when you add daratumumab to existing backbone [therapy].

The first study that was published came out in 2020 in the Blood journal, and this is from the randomized VRd [bortezomib, lenalidomide, and dexamethasone] plus daratumumab vs VRd. This is the GRIFFIN trial. Patients got 6 cycles of combination therapy and a bone marrow transplant. If it was with the daratumumab arm, patients could achieve MRD negativity at the rate of 51% in the intention-to-treat analysis. And for the VRd alone with a bone marrow transplant, this was 20% MRD negativity, also in the intention-to-treat analysis.

We published daratumumab added to carfilzomib, lenalidomide, and dexamethasone, the KRd regimen—weekly KRd. That came out very recently in the JAMA Oncology journal. We showed 8 cycles of weekly KRd with daratumumab was found in 71% of patients, they were MRD negative, and this is without bone marrow transplants.

I think we will continue to see very high rates of MRD negativity with daratumumab added to various combinations.