Overview of Cytokine Release Syndrome in Relapsed/Refractory Multiple Myeloma


Experts Thomas Martin, MD; Ajay Nooka, MD; and Jeremy Larsen, MD, provide a broad overview of cytokine release syndrome as it relates to the management of multiple myeloma.


Thomas G. Martin, MD: Hello. I’m Dr Tom Martin from the University of California, San Francisco [Helen Diller Family Comprehensive Cancer Center]. We’re going to have a journal club experience. Joining me are Dr Ajay Nooka from the Winship Cancer Institute of Emory University [in Atlanta, Georgia], and Dr Jeremy Larsen from City of Hope Phoenix in Goodyear, Arizona. We’re going to talk about an article that was recently published. Dr Nooka and I were coauthors of this article, titled “Detailed Overview of Incidence and Management of Cytokine Release Syndrome Observed With Teclistamab in the MajesTEC-1 Study of Patients With Relapsed/Refractory Multiple Myeloma.”Welcome, Dr Nooka. Welcome, Dr Larsen.

Jeremy Larsen, MD: Thanks for having me.

Thomas G. Martin, MD: Have you guys had a chance to look over the article and read it?

Ajay Nooka, MD, MPH, FACP: Absolutely.

Jeremy Larsen, MD: Absolutely. It’s a great study.

Thomas G. Martin, MD: Wonderful. Hopefully it’s made a dramatic difference in your clinical practice. We’ll get into that as we go along. As you know, the bispecific T-cell–engaging antibodies have taken myeloma and some other disorders by storm, which is awesome. One of the main things that happens as a sequelae of treatment with these T-cell–redirecting antibodies is a novel toxicity that we didn’t have prior to bispecifics or CAR [chimeric antigen receptor] in multiple myeloma, and that’s cytokine release syndrome [CRS]. Dr Nooka, go over with us how CRS is diagnosed. Then Dr Larsen, tell us how it’s graded and how you do that at your institution.

Ajay Nooka, MD, MPH, FACP: Cytokine release syndrome is a systemic inflammatory response to any antigen-mediated immune stimulation. With any T-cell–directed therapies, we’d see it with postallogeneic stem cell transplants, especially the haploidentical transplants. We’d also seen it with the CAR T-cell therapies. Now we’re seeing it more in the bispecific therapies. Anything that’s stimulating the T-cells and the immune system can present as a CRS. How does it clinically manifest? You see all the symptoms related to inflammation: fever, hypertension. Anything sepsis looking in the right context among patients who received a T-cell–directed therapy should be considered a cytokine release syndrome.

Thomas G. Martin, MD: Go ahead, Dr Larsen.

Jeremy Larsen, MD: I agree 100%. In terms of the spectrum of disease we see, this has become mainstream based on the ASTCT [American Society for Transplantation and Cellular Therapy?] data. A lot of this piggybacks on our experience from CAR T. With the bispecifics, although CRS is frequent, [it has] much less severity. In my mind, grades1 to 2arelow-grade CRS, and that’s usually quite manageable. We start to get into grades3 and 4, which fortunately is quite uncommon with things like teclistamab and other bispecifics. That’s usually where intensivists are becoming involved, and we’re seeing things like hemodynamic instability. In general, grade 1 is isolated fever. In grade 2 we start to see soft signs, things like mild hypoxia, which is generally enough to be supported by supplemental O2[oxygen] without high flow and perhaps fluid-responsive hypotension. Then we move into more significant hemodynamic instability. For example, in grade 3 we’re talking about using vasopressor support or high-flow oxygen. Patients are usually making a trip to the ICU [intensive care unit].Grade 4, obviously, is where we’re seeing end-stage hemodynamic collapse, which fortunately we don’t tend to see. But as we’ll highlight today, proactive management will hopefully be able to keep patients in that first category, grades1 to 2.

Thomas G. Martin, MD: With the T-cell engagers, it’s usually mini CRS. I can’t say we’ve had to move anybody to the intensive care unit at UCSF, but you have to be prepared because it can happen. Grade 3 ICU care has been described but is less common. Some of some of the practitioners will also remember when we used to give high doses of IL-2 because a lot of the cytokines are way high during this. We used to give high doses of IL-2 and see a cytokine storm with fevers and hypotension. Back in the day we were using therapeutics that weren’t as directed as [the ones] we have now. We’ve moved on to T-cell engagers, etc. For the places that do haploidentical transplants, soon after you start having fevers and seeing the cytokine release. Once they get high doses of cyclophosphamide, it goes away quickly, so we’re knocking down all those T-cells. Thankfully, we don’t have to treat these patients with high-dose cyclophosphamide also.

Transcript edited for clarity.

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