Daratumumab vs Lenalidomide As Myeloma Maintenance Therapy | Sridevi Rajeeve, MD | #ASH24

My name is Sridevi Rajeeve. I'm a multiple myeloma and cell therapy doctor at Memorial Sloan-Kettering Cancer Center in New York City. Here at ash, on behalf of the whole team at Memorial Sloan Kettering, we are actually presenting data on comparing daratumumab, which is a monoclonal antibody used in multiple myeloma in a head to head comparison with lenalidomide, which is a pill that is also used in the management of multiple myeloma.

So this is a study which was an investigator initiated this study that we did at MSKCC in which we compared daratumumab and lenalidomide head to head. And that's not been done in a trial format before in, you know, in around the world. So we felt it was an important question to answer. But what's the background behind it? In multiple myeloma patients often undergoing intensive therapy called induction therapy, which may or may not be associated with stem cell transplant.

And that's always followed by something called as a maintenance phase. And in the maintenance phase. As of now, the standard of care for most patients, but not some patients, is maintenance with a pill called lenalidomide. Now, lenalidomide has been in the market for many, many years. We're talking about decades and many trials therefore focus on lenalidomide as the main backbone.

However, you know, since we have a lot of patients on lenalidomide backbone for many, many years, we are now starting to understand that it's not the easiest pill to swallow, so to speak. Right. You know, we have a lot of side effects such as diarrhea, rashes, peripheral neuropathy. There's also a remote possibility of increased risk for secondary malignancies.

So in this era of new treatments we wanted to see if daratumumab which is actually a subcutaneous or under the skin injection that can be given, you know, in a decreased frequency manner as once a month. Is that equivalent or superior to lenalidomide and can it replace lenalidomide in the maintenance setting. So that was our study. So in this abstract we summarized in this head to head format how they were compared.

There were around 39 patients in the daratumumab arm and 38 patients in the lenalidomide arm. What we really found was that in a nutshell, the lenalidomide arm did not really outperformed daratumumab. In fact, daratumumab really emerged for important metrics like progression free survival, measurable residual disease or MRD negative status, complete response, or stringent complete response on all important metrics.

Daratumumab emerged as a winner and establishing its efficacy as equivalent and mildly superior to lenalidomide. But the important aspect we also wanted to focus on was safety. Is Daratumumab sure it's equivalent or better than lenalidomide, but is it safe? Is it less toxic than lenalidomide? And what we are seeing is that in a safety signal, daratumumab is extremely well tolerated.

The rates of discontinuing daratumumab are much, much less than that of lenalidomide. The main causes for discontinuing daratumumab we only had three patients discontinue. And so far the nearly 40 patients we had on one had a new diagnosis of another cancer, so we discontinued. There was also one incidence of pneumonitis and one the incidence of infection. On the other hand, we had nearly double.

We had nearly six patients discontinue lenalidomide in the 3 to 4 years of this trial, and most of them were due to intolerance due to significant peripheral neuropathy, one due to diarrhea and one due to a severe whole body rash. So what we are clearly seeing as a signal is that Daratumumab can be an effective replacement as a maintenance treatment for those patients who are intolerant to lenalidomide.

And in future, with the Cassiopeia study, the ALCYONE study and recently at Ash 2024, the Auriga study was also presented, all focusing on Daratumumab as a maintenance strategy in lieu of lenalidomide. So our study is adding on to the literature. It's a direct head to head comparison against standard of care. So I really think that in the future, Daratumumab is going to be a good option for patients in the maintenance setting for those who want to avoid the deleterious effects of lenalidomide.

So with all these trials that are actively looking into daratumumab in the maintenance setting, and once our trial also reads out, I'm sure the sponsor and the pharmaceutical company will move to request, you know, an expanded indication for daratumumab. I think in the next two years we may have an official indication, but there's a lot of off label use for intolerance being done anyway.

So in our clinics, we are already using someone's intolerant to lenalidomide. We often go to their tumor map, but once we have an official indication by the FDA and it makes it into the NCCN guidelines as an official replacement, then there will be much more adoption. I think we are maybe two three years away or even less.