Clinical Pearls on CRS and ICANS Management in Multiple Myeloma


Moderator Ajai Chari, MD, leads the panel in sharing clinical pearls for management of CRS and ICANS in multiple myeloma before closing out the final module.


Ajai Chari, MD: These cases have brought up a lot of important topics to summarize but also expand. We’ve heard about the CRS [cytokine release syndrome] and ICANS [immune effector cell-associated neurotoxicity syndrome] recognition and the importance of REMS [Risk Evaluation and Mitigation Strategy] program and training, doing a prompt vital signs [exam] by the floor team. Once the frontline provider is called, we consider order sets, including vitals, labs, and therapeutics. [We also consider] timely drug administration: mixing and coordination with pharmacy and nursing. [We also have] all those consultants: neurology, neuroradiology, ICU [intensive care unit], infectious disease, ERs [emergency departments]. In some centers, patients get risk bands to indicate that they’re on T-cell redirection therapies so ERs won’t be caught off-guard that this requires some special understanding. That’s a sample of the orders we have at Mount Sinai [Hospital]. Robert, you’ve alluded to this. Is there anything you want to tell us about REMS implementation at your institution?

Robert Mancini, PharmD, BCOP: The biggest thing is having 1 individual coordinate everything. When you expect everyone to do things on your own, you don’t always know whether it’s getting done and whether things are being tracked appropriately. This 1 isn’t that extensive compared with other REMS programs I’ve dealt with, but making sure all those pieces are getting done is important. When those companies come in to audit you for your REMS and you can’t prove compliance, that may increase the risk of you not being able to continue use of this drug. Making sure that there’s coordination, someone is overseeing that, ensuring all components are being adhered to is crucial for access for these patients.

Ajai Chari, MD: Annel, you’ve talked about educating your colleagues on the floors, but let’s face it: they’re working in shifts, and not everybody comes to the training. How do you capture everybody with education? What strategies do you have?

Annel Urena, RN: When it comes to education, there are peak modules that the nurses have to complete once they receive these type of patients, to have this education accessibility. When it comes to vital sign frequency, as a nurse, it’s critical thinking. Your patient receives this new medication and you’ve already been in service or you’ve done your education on the actual drug and its management. If any toxicities are noted, you have to think if your patient is giving you new reports of onset of symptoms, vital signs are usually 1 of the first things that gets affected. You need to make sure the frequency or monitoring is prioritized.

As a floor nurse, things happen. There’s short staffing, or maybe they didn’t receive the education. But as a nurse, having that patient, make sure you educate your assistants who are assisting you. Make sure they’re doing the vitals. For anyone who’s covering for you, making sure everyone is on board and monitoring the patient whenever something is arising or the patient is reporting new onset of symptoms.

Ajai Chari, MD: Other institutions may have different strategies, but peak modules are our effort to do online training [Mount Sinai Hospital]. In the era of online education, this can come in the format of a Zoom service that could be recorded and watched at a nurse’s leisure or a written slide set that we’ve documented. Shift based work and patient staffing shouldn’t be a barrier to educating the very broad and important component of frontline nursing. Once the nurse calls for the frontline provider, it could depend on the hospital. It could be a resident who’s moonlighting, it could be a hospitalist who may not be a hematologist oncologist, it could be an NP [nurse practitioner] who may or may not be in hematology oncology. Kiah, how would you suggest capturing and training these individuals on what to do once they’re called about CRS?

Kiah Purcell, NP: The online modules are a great option. Hopefully those individuals did the REMS program. The whole point of the REMS program is so everyone at the institution is educated, everyone who’s touching the drug is educated on adverse effects—what to look for so we don’t miss critical things. As far as educating, there needs to be good inpatient and outpatient education depending on where the medication is given. I never have a problem doing a 1-on-1 with another staff member. Even if I don’t have the time, I’d rather everyone knows the medication and understands what they’re looking for. If I’m not going to be here and there’s night coverage for 1 of our patients, I’ll call them and say, “This is what we’re looking for. If this happens, you need to call this individual. You’ll probably need to order tocilizumab.” I’ll walk through it with them, but not every institution or individual has the bandwidth to do that. We’re all very busy, so training everyone in the hospital 1-on-1 isn’t an option.

If someone missed [training], I have no problem going through that, so they know that when they are called and they’re seeing fever and tachycardia and hypotension. They’re used to looking for sepsis, so it’s important to rule out sepsis, but there’s this other thing they need to be thinking about, which is CRS. If it’s 1 of those individuals who is moonlighting, they might not know what CRS is or how to manage it. They need to know what the treatment is and if there’s somebody else they can call if they have questions.

Ajai Chari, MD: Our first bispecific started in 2017. In the 6 years that we’ve been doing bispecifics, I’ve gotten more phone calls at inopportune times of the morning than I got in my entire 12 years prior to that. These CRSs are not happening at convenient times. For that reason, we created this order set at Mount Sinai where we increase the vital sign frequency, limiting the number because we have to be compliant with hospital rules. If you do incessant vital signs every hour, you should be at a step-down unit. For a fixed duration, you could do more frequent vital signs. There’s a CRS order set, and there are drop-down boxes for tocilizumab, anakinra, corticosteroids, and … If you’ve never given tocilizumab before, will somebody know that it’s 8 mg/kg IV [intravenous] times 1? Or will they wasting time looking for that? With seizure prophylaxis, [we treat] with Keppra, a nonsedating drug, and everything is prepopulated. I’d love to hear Robert’s thoughts because the pharmacist who’s covering these patients at night may never have had any interaction with a bispecific or tocilizumab. Any thoughts on educating your pharmacy colleagues around the country?

Robert Mancini, PharmD, BCOP: The biggest thing in those after-hours situations is making sure they understand the acuity of this situation. I’ll talk about this in terms of that call to help them understand. Look at something like tocilizumab. It’s not difficult to prepare. It’s already in solution. You just take it out, shoot it in the bag, prepare it, and get it out to the floor. If they just put that in the queue with all the other things they’re doing, then that could lead to delay. The biggest thing we do in educating other pharmacists on our inpatient side is making sure they understand that if they get this call, there’s that acuity. Going back to that order set, when you build something like the tocilizumab into that, there’s information in the … that talks about acuity, indication, and factors that are important. That way, whoever sees the orders can understand that component of things. It’s not just the education but also that follow-up and how you build things out and make it as clear as possible in the orders.

Ajai Chari, MD: If there’s a delay in the nurse recognizing and doing the vital signs, if there’s a delay in calling the frontline provider, if there’s a delay in the frontline provider recognizing CRS, if there’s a delay in them putting the order, and if there’s delay in pharmacy getting that and then giving it back to the floor nurse, that chain can be broken at any of those points. A lot of that will happen without the primary myeloma doctor. The individual getting called may not even be the individual who did the REMS from the myeloma perspective. This order set does have that stat. We should be thinking about CRS and ICANS almost like febrile neutropenia. You should be assessing, dosing, and intervening promptly. Kiah, over the years you’ve had to work with a lot of subspecialty consultants from various departments. Can you tell us about your experience? When do you get specialists involved, such as neurology?

Kiah Purcell, NP: We’re at a large academic institution, so we get individuals involved very early. They’ve helped develop our understanding of these drugs. With ICANS, we often refer to neurology if it’s not resolving and there are still issues, especially with teclistamab infectious disease, cardiology, gastroenterology. We refer to everyone because they help us manage the adverse effects of these medications and come up with protocols on how to treat them.

Ajai Chari, MD: One other point is that tocilizumab is a monoclonal antibody, and some hospitals have restrictions on which floors and nurses can administer monoclonal antibodies. It’s another kink to work through. If this patient is sick enough to go to a step-down unit or an ICU, are those nurses trained in tocilizumab administration? Robert, any comments on monoclonal antibodies at [St. Luke’s Cancer Institute in] Idaho?

Robert Mancini, PharmD, BCOP: Another important point about that chain of timing is that we can’t tube monoclonals. We can’t make it in the pharmacy, shoot it up there. You still need someone to deliver it or pick it up to help with that transport. That’s something else that you need to keep in mind. To your other points, you have those restrictions in place.

Ajai Chari, MD: This has been an exciting discussion. We’ve been talking about BCMA bispecifics, but the next up is probably going to be talquetamab GPRC5D. Soon thereafter will probably be an FCRH5 cevostamab. This means that we’re going to have a choice of 3 targets, and sometimes multiple agents but the same target—with BCMA, for example. It’s going to be incumbent on us as a health care team to educate ourselves and our entire system about each of these bispecific antibodies and how we pick among them. If you get 1 target, you may want to switch targets. Another thing we need to understand is from ASH [American Society of Hematology Annual Meeting] 2022. When you treat somebody with a bispecific, they may experience T-cell exhaustion at the end of that bispecific. What are the translational data and correlatives that might guide this next line of therapy?

Perhaps we want to alternate to an antibody-drug conjugate or CELMoD to give some break for T-cell recovery. These are all things we need to work out, but it’s a super-exciting time when you have multiple products with 60% to 80% response rates for patients who were hospice bound. It’s an incredible, rewarding time in myeloma. All of our standard-of-care teams think every patient is responding to commercial teclistamab, and these are train wreck patients who couldn’t go onto a study. It looks like magic. That’s how dramatic the patient benefit is.

I want to thank our entire team for an engaging, interactive discussion highlighting the important interdisciplinary nature of myeloma care, specifically with T-cell redirections and bispecifics. This has been extremely informative. Thank you all for this insightful discussion, and thank you to our audience for watching this Cancer Network® Training Academy session on bispecifics in myeloma. We hope you found this useful and informative. Thank you for your attention.

Transcript edited for clarity.

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