Myeloma Maintenance: Daratumumab as an Alternative to Lenalidomide | Sridevi Rajeeve, MD

Hi, my name is Sridevi Rajeeve.

I'm a multiple myeloma and cell therapy specialist at the Memorial Sloan-Kettering Cancer Center in New York City.

Here at ASH 2025.

We are proud to present, on behalf of Memorial Sloan-Kettering, the first and only randomized trial that looks at daratumumab versus lenalidomide in the maintenance setting for patients with newly diagnosed multiple myeloma, including looking at the quality of life metrics, efficacy as well as safety.

In essence, this was an investigator initiated trial that was designed at Sloan Kettering five years ago.

89 patients were accrued and fully dosed with either daratumumab or lenalidomide, and this was the first and only study that has ever looked at these drugs, which are quite active in the maintenance setting, head to head.

Now, the background is that the standard maintenance therapy, not just in the United States, but quite across the world following stem cell transplant is that of lenalidomide.

However, lenalidomide, for any patient who has been on it, it's not an easy drug to tolerate. For most.

You know, there are issues like skin rashes, diarrhea, you know, blood clots and all of that which cause infections which cause patients to discontinue the drug early on.

So we decided to look whether daratumumab, which was anti-CD38 monoclonal antibody which has been studied in the Cassiopeia trial, the Perseus the Griffin trial, Cepheus trial, Auriga trial.

Many of these trials as a combination, whether as a monotherapy, this can be used in the maintenance setting and compare it against the standard of care, which is lenalidomide, and especially, you know, with it, keeping in mind that for patients who have lenalidomide intolerance or some form of resistance, can daratumumab be a replacement.

So we did this clinical trial.

89 patients were on board.

There were 44 on the daratumumab arm, 45 on the lenalidomide arm.

The top line results were that can be divided into three.

One is quality of life which was one of our primary endpoints.

And in the primary endpoint we did see that while there were no differences in global health score across daratumumab or lenalidomide arm,

there were slight differences in the subgroups or quality of life, including the daratumumab arm, unsurprisingly, having less diarrhea, less insomnia, and in general, a little bit more tolerance.

I think patients did prefer the monthly injection, probably over a daily pill, which caused them other forms of distress, so that was our primary endpoint.

We also looked at efficacy as well as safety for efficacy metrics.

There was a numerical increase in efficacy in both overall response rate, complete response rate, and VGPR rates for the daratumumab arm.

However, we cannot draw conclusions because the study was just not powered for it.

But we do see a numerical trend and an increase in response, increase in progression free survival, and an increase in MRD negative response on single agent daratumumab versus single agent lenalidomide.

Regarding safety, there were more serious adverse events in the daratumumab arm specifically for infections.

Again, unsurprising because we know that as a class, anti-CD38 monoclonal antibodies are known to have infections.

However, the lenalidomide arm was notable for higher diarrhea as well as, you know, higher incidence of second primary malignancies.

Overall, taken together, this study is showing us that, you know, lenalidomide while it continues to be a standard.

And while it's evolving via now in the era of dual maintenance or even continuous maintenance for those subset of patients for whom you're still considering lenalidomide,

and for exact those patients who are unable to complete their course of lenalidomide, one may consider daratumumab as a safe alternative that does not have any impact on quality of life.

And maybe, you know, we don't have again, we're not powered for it, but equivalent efficacy.

So a real alternative single agent alternative to lenalidomide.

And this is especially prevalent for not just the Western Hemisphere but for the rest of the world where single agent maintenance is what is regularly being done, taking into consideration financial constraints.

So if you're thinking about a single agent maintenance, if lenalidomide is being not tolerated by the patient.

Daratumumab based on the results of this randomized phase two study, can be considered as an alternative.

If our videos have helped you in any way and you're able to, please consider making a donation to help us continue this important work.

Your gift will go three times as far when we reach $500,000 by the end of the year.

Every contribution, big or small, makes a difference

and we're deeply grateful for your support.