Elranatamab Active in Relapsed or Refractory Multiple Myeloma

News

Data presented at the 2022 American Society of Hematology (ASH) annual meeting showed that elranatamab induces responses in relapsed or refractory multiple myeloma, and has a manageable safety profile.

In this exclusive MedPage Today video, Noopur Raje, MD, director of the Center for Multiple Myeloma at Massachusetts General Hospital in Boston, outlines the results of the study.

Following is a transcript of her remarks:

I presented data on MagnetisMM-1 at this year’s ASH meeting. MagnetisMM-1 is a first-in-human study on the use of a bispecific monoclonal antibody directed against BCMA [B-cell maturation antigen] — in this case, elranatamab.

What we presented was experience in the 55 patients in our first-in-human effort. This was a dose-escalation study. We started with 215 mcg, and went all the way to 1,000 mcg. Obviously, the primary aim here was to look at toxicity, and then we looked at efficacy as well. We did do pharmacokinetics and pharmacodynamics.

And what we found was that with the recommended phase II dose of elranatamab, there was a nice dose-response curve. When you look at the pharmacokinetics, we looked at weekly dosing as well as dosing every other week, and they kind of mirrored each other in terms of dose response.

This was a study done in pretty heavily pretreated patients. On an average, the median lines of treatment here was five. They’d all been previously exposed to a proteasome inhibitor, an immunomodulatory drug, and 100% of them had seen an anti-CD38 monoclonal antibody.

What was different with this BCMA bispecific T-cell engager was the fact that we did allow for previous BCMA exposure as well. And we had about 23% of our patients who had had a prior BCMA drug product given to them. Obviously, we weren’t allowed to give a bispecific, so the majority of patients had had either an antibody drug conjugate or in fact CAR T-cells. And in fact, some of them had had both antibody drug conjugate as well as CAR T-cells.

So the good news is we saw a pretty significant overall response rate of about 62% with a complete response and a stringent complete response of approximately 38%. When you look at those who had been previously treated with the BCMA-directed strategies, we still saw high response rates, albeit a little bit lower than what we saw in the general population.

The overall response rate in that patient population was about 54%. These responses were deep — specifically when you look at those who’d achieved a complete response. We were able to look for MRD [minimal residual disease] in about 13 of these patients, and 100% of them were MRD-negative, and at a follow-up of 6 months, about 64% or so continued to be MRD-negative.

Looking at the duration of response of all responders, it was about 17 months and the median progression-free survival though was a little over 11 months.

From a toxicity standpoint, very well tolerated. Expected toxicity of cytokine release syndrome [CRS] was seen with this bispecific T-cell engager, but again most of the CRS was grade 1 and grade 2 and was easy to manage. We did not really see any ICANS [immune effector cell-associated neurotoxicity syndrome] or neurotoxicity with this.

And subsequently we did present our MagnetisMM-3 experience as well. This is the phase II sort of follow-up study to MagnetisMM-1, and Dr. [Nizar] Bahlis presented data on 123 patients. This was in the cohort which was not previously BCMA exposed. We do have a separate cohort of BCMA-exposed patients, which we will present at a future date. And the results of the phase II trial really mirrored what we saw with the phase I trial. So really reassuring that once you went to 123 patients, the data was actually confirmed in this first-in-human trial.

I think this year’s ASH was really dedicated to bispecific T-cell engagers, and this is really timely because we have our first-in-class T-cell engager already approved. This was only about 3 weeks back, where we have teclistamab [Tecvayli] approved — very similar data, very similar results, maybe some differences in toxicity, but it’s hard to cross-compare across trials. We have now a second bispecific T-cell engagement in that same class. And really I think this is, would be, huge once this gets approved for our patients, because these are off the shelf and there is really no waiting time like we have for CAR T-cells, etc.

We did hospitalize patients for the first week when we did the step-up dosing with all of these T-cell engagers, whether it’s teclistamab or elranatamab. And I think logistically we’ll have to work out the details of how we incorporate this into clinical practice.

  • author['full_name']

    Greg Laub is the Senior Director of Video and currently leads the video and podcast production teams. Follow

Articles You May Like

Migraine Associated With Increased Risk Of Preterm Delivery, Preeclampsia: Study
The Innate Immune System: Advancing Understanding
Most US Adults Want Sale Of Menthol Cigarettes, Tobacco Products Stopped: Survey
Financial coaching for parents in pediatric primary care reduces missed well-child care visit rates
Self-growing bricks could change future space exploration

Leave a Reply

Your email address will not be published. Required fields are marked *