BCMA-Targeted Therapy for Relapsed/Refractory Multiple Myeloma - Episode 5

BCMA-Targeted Therapy in RRMM: Management of Adverse Events

Nina Shah, MD:Different mechanism of action. Maybe same target, but different mechanism of action. So I think it’s worth sequencing then, at least trying it, because these patients do need other options after the CAR [chimeric antigen receptor] T-cell failure.

Ola Landgren, MD, PhD:Coming back a little to the practical aspects of the use of the ADCs [antibody-drug conjugates], compared with the CAR T cell therapy, we talked about the differences in the study design, the patient populations, and that they were more heavily pretreated. They probably were a little thicker, the CAR T-cell patients. But once these drugs are FDA approved, the antibody-drug conjugates, what would be, in your view, the clinical benefits using such a drug over the cell therapies?

Nina Shah, MD:Yeah. There is exactly what you’re saying. It’s an entirely different treatment approach, right? For the cellular therapy, you have to go to a specialized center, have a whole process of cell collection, and then the cells have to be engineered and you have to come back, and sometimes there’s bridging chemotherapy between those 2 steps. But most important, as of now you will have to be treated in a center that has been approved to give these therapies, that knows how to manage cytokine release syndrome, knows how to manage cellular therapy toxicities and potential neural toxicity. Whereas with the ADC, that’s definitely an option for community-friendly treatment. Meaning this drug could be available at a community practice. In that situation, it’s more being acquainted with the toxicities of that drug, which tend to be outpatient-related toxicities.

Ola Landgren, MD, PhD:Let’s talk a little about the toxicity. We talked about the fact that the first study showed 60% overall response rate, which is very good. When it came to the toxicity at the presentation so far, as well of the paper that was recently published, including the expansion cohort, the 2 main toxicities that stand out when I read the literature are the thrombocytopenia and also the blurry vision. Can you give some more detail on that?

Nina Shah, MD:Yeah. These are the top 2 toxicities. And there was even grade 3 thrombocytopenia with this drug. I guess as hematologists—and I’ll just say my own bias, sometimes I don’t worry so much about thrombocytopenia because I’m so used to managing it—what’s really striking about this particular drug is it does have ocular toxicity. And I believe 60% to 70% of the patients in this study experience some kind of ocular toxicity. The good news is that with mainly grade 1 or grade 2, there were very few grade 3 events for this particular thing, but the last good news is it’s ocular toxicity. And this does mean that there is some supportive care that has to be done, and it has to be known by the community physician or by whoever the treating physician is, in order to manage this.

What they did was they used steroid drops very judiciously to prevent these types of toxicities. They did require treatment interruptions during the time that somebody may have had an event and had to pause, but then they could go back on treatment. Actually, there were a good number of patients who did have treatment interruptions. Then they’re looking at other things in the future like pulling mass and different types of steroid drop regimens or schedules to ameliorate this.

Ultimately it might be nice to have a collaborator in a local practice, somebody who you know is referring for ophthalmology, or even an optometrist to be able to measure this. But really listening to how the patients are feeling about it.

Ola Landgren, MD, PhD:I talked to some colleagues of mine at Memorial Sloan Kettering Cancer Center who treat other malignancies, including a hematology specialist, and I think there were other parts of the field in the oncology space where there are ocular toxicities that have been around for a long time. Other doctors in this field for a long time have had the collaboration with ophthalmologists. It’s not a new thing, from a little bit of a bigger picture.

Nina Shah, MD:Right, exactly. And which is actually pertinent because not everybody is just a myeloma doctor. They’ve already had that experience as a general oncologist, and you will not be as worried to use this drug. You know who your collaborators are; you know what to expect.

Ola Landgren, MD, PhD:When it comes to this ocular toxicity, you emphasize that I think that’s important, that they are grade 1 and grade 2 based on the current knowledge from the papers and ongoing studies. Also that it’s reversible. I think that’s very important to emphasize.

Nina Shah, MD:Right, yes. It is reversible.

Ola Landgren, MD, PhD:It seems that the blurred vision—from my clinical experience and from our center, I think we have had patients in 1 or 2 weeks. But I think there is also some dialogue saying that this could even continue to reverse up to a month or something like that.

Nina Shah, MD:Yeah, and it varies between patients.

Ola Landgren, MD, PhD:Yeah. I think we have had patients who had some blurred vision on some of the studies that were holding therapy, and then they resumed therapy again and the symptoms were much less.

Nina Shah, MD:Right.

Ola Landgren, MD, PhD:I think there was more work to be done, but I think these are important nuances that it’s not high-grade and it’s reversible. I think that’s important.

Nina Shah, MD:Right. And like all drugs that we used, I would imagine carfilzomib, daratumumab, and all these drugs that took a little bit of learning-curve time but now are very commonly used, not only in academic centers but basically everywhere. I think all these things take experience, and us as a community, we have to make sure we put our experiences together, report on these, talk to one another, figure out how to manage these things. Ultimately because if it works and it’s giving a PFS [progression-free survival] at 12 months, it is up to us to try to implement these types of drugs.

Ola Landgren, MD, PhD:I think that’s very well said. It really works, so there is some work that needs to be done to kind of figure out exactly how to use it and how to manage clinically.

Transcript edited for clarity.