A roundtable discussion, moderated by Thomas Martin, MD, Blood Cancers Today Associate Editor, of the University of California, San Francisco, focused on bispecific therapeutics for the treatment of multiple myeloma. Dr. Martin was joined by Ajay Nooka, MD, MPH, FACP; Ajai Chari, MD; and Angela Dispenzieri, MD.
In the next segment of the roundtable series, the panel addresses side effects that are commonly seen in patients receiving bispecifics, most notably cytokine release syndrome, and how to manage them.
Watch the next segment in this series.
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Dr. Martin: These obviously have some novel toxicities. We can start with CRS [cytokine release syndrome], etc. Ajai just said that it mandates at admission, but does it, Angela? Tell us how you do it at the Mayo Clinic.
Dr. Dispenzieri: Yeah, so we’ve been looking a lot at remote monitoring where you give a patient a box of supplies for blood pressure and heart rate and temperature monitoring. We do start all our patients currently according to the REMS [Risk Evaluation and Mitigation Strategies] as an inpatient. But then when we dismiss them, we are in contact through the remote monitoring practice. There is talk that soon we are going to not be necessarily admitting all patients now for our bispecifics. Again, that’s not exactly REMS, but so far, as long as we’re kind of watching them for those first few hours and they’re sent home with their monitoring and educated to let us know if there’s anything because we have a very strong, we do outpatient BMT [bone marrow transplant], we do a lot of outpatient hem/onc kinds of things. We have sort of 24/7. They don’t go to the ER; they actually come to our unit. Then there’s one less grouping that you have to train in terms of how to react. It’s less about the ER physicians. They’re all coming to our station. That’s working. It’s been working quite well, and we’ll kind of see where it goes.
Dr. Martin: That’ll be really interesting. Look out for a couple abstracts. We have one here at SOHO [Society of Hematologic Oncology]. We have one at IMS [International Myeloma Society] and we have one at ASH [American Society of Hematology]. Yi Lin, MD, from Mayo Clinic and I have been working with the IMF [International Myeloma Foundation] to try to do real-world analysis of teclistamab. It’s very different the way actually it happens at Mayo Clinic where they’re outpatient and with us where they’re inpatient, which is really interesting. For us, we do admit them. We admit them for the seven days; dose them on day one, three, and five for the first two step-up doses in the first full dose and then we send them home. But CRS [cytokine release syndrome] management as we talk amongst colleagues around the world is a little bit different. Ajai, how do you do CRS management? How did you do it at Mount Sinai? And then how are you going to do it at UCSF [University of California, San Francisco]?
Dr. Chari: Well, there was an email about that, right? To standardize it across all the malignancies with the lymphoma and myeloma.
We have to keep in mind that the dosing and schedules can be very different across the products. Currently, all three of these have step-up doses, two or three for talquetamab, depending on which dosing you’re using. Talquetamab has 0.4 weekly, which has two step ups before final dose or 0.8 every two weeks, which has three step ups. That is a longer hospitalization if you’re doing it back to back. I bring that up because then tocilizumab being a monoclonal antibody is a long half-life. I think one of the things we’re seeing is if you give tocilizumab early, you have less recurrent CRS and it probably can shorten that duration of hospitalization because before you clear a patient for a subsequent dose, they need to have resolved the CRS.
If you give it, I personally am a big fan of early tocilizumab because the first fever, when you have multiple step-ups following, you’ll just get… I don’t like drama. Squelch the drama early; pull the tocilizumab trigger. I think some people give Tylenol/acetaminophen with it. Some people also I know do dexamethasone instead. I think we heard the CIVO, which is targeting FcRL5 not yet approved, but they presented prophylactic tocilizumab that showed that the rates of CRS dropped significantly, but there was more neutropenia and it didn’t drop the grade 3 and higher CRS. I think that’s the concern with, I think clearly we’ll hear Emory’s data too, but I think early tocilizumab personally for these. The only caveat I’ll make is there are some other bispecifics being studied in myeloma that are weekly step up. There, I’m not sure how much tocilizumab will help because if you’re not going to the next step up for a week, you might get away with a little acetaminophen and dexamethasone. But for now, for these ones that have tightly packed step up, I think early tocilizumab, I’m a big fan. I don’t know if the group agrees.
Dr. Martin: We’ve talked about this in our International Myeloma Working Group meetings, and it really was split—split between those at early tocilizumab, let’s give them the tocilizumab with the first fever, try to take the fever away. Especially as we do older patients where you don’t really want them being febrile for multiple nights. Because it does happen all at night. Then they get confused, then they get delirium, and then you’re worried, is it ICANS [immune effector cell-associated neurotoxicity syndrome], is it delirium? What is it? Turn it off quick. Again, then you have less recurrent CRS following next doses. Versus the other camp that said, well, we can use dexamethasone. Let’s use dexamethasone and let’s hold tocilizumab until they really have grade 2 CRS. There really were two emerging camps. Anything different at Emory?
Dr. Nooka: We have started to go with Ajai basically trying to see how can we minimize the risk of CRS getting worse by early incorporation of tocilizumab. What we have done as a practice measure with an intent to change to outpatient administration. We looked at the first 15 patients that we treated. We looked at the median time to having a CRS. That came down to 46 hours just prior to the second dose. What we have tried to do is can we prevent that from happening by giving tocilizumab two hours before? The 44-hour mark for the next 36 patients that we treated, we went ahead and gave the prophylactic tocilizumab, which eventually turned out a third of the patients, 30% of the patients, 10 patients of these 36 patients had a CRS. All of them are grade 1, and there is no grade 3 toxicity, which is allowing us to say if we give it prior to the second dose, you probably are minimizing the risk of a worse CRS.
The biggest concern that people against tocilizumab, number one, it increased the risk of neutropenia, could it increase the risk of infections? We looked at it very, very closely. Our data does not show that to be the case with one dose. There is no higher-grade toxicity with CRS; there is no increase in the readmit dates. Even by preventing an extra day of hospitalization, you offset the cost of tocilizumab, which is very cheap. Altogether, it makes the case for us to do this and right now we have data for all these patients. We want to move to an outpatient setting. The caveats that we had in terms of why we did not move to an outpatient setting is we didn’t have a 24/7 coverage like Mayo has and physiological monitoring. Right now, once the AIC [advanced infusion care] is open for us 24/7, it becomes so much easier for lymphomas, for myelomas, all the bispecific antibodies to be treated the same way as an outpatient administration.
Dr. Martin: Some people have started to use prophylaxis, but that’s a new twist. It’s prophylaxis after the first dose. Is that right? That’s a new twist. I like that.