Management of ICANS Associated with Bispecific Antibodies in MM
A brief review of available management strategies used in practice when patients with multiple myeloma develop immune effector cell-associated neurotoxicity syndrome.
Transcript:
Ajai Chari, MD:Kiah and Robert, how do we manage these based on the grading? What’s your go-to when you start with ICANS [immune effector cell-associated neurotoxicity syndrome]?
Kiah Purcell, NP: When we start with ICANS, our go-to is dexamethasone, especially in the case we just discussed because she was still having fevers as well. I definitely want to intervene at that point. We usually do dexamethasone for grade 1, even though you can observe depending on what the other clinical symptoms are. If the dexamethasone isn’t improving or there are other symptoms, we move to anakinra pretty quickly.
Ajai Chari, MD: You bring up an important point with tocilizumab and dexamethasone: early intervention. We have to keep in mind that we have these step-up doses. If you don’t address this, you may not be able to give your next dose on time. What’s the point of waiting? It’s not like we’re done with this drug’s step-up process. I agree completely: early intervention makes a big difference. Robert, with especially CAR [chimeric antigen receptor] T cells, we tend to see more of the high-grade issues in ICANS. What are some additional considerations you want to recommend if dexamethasone alone isn’t enough?
Robert Mancini, PharmD, BCOP: One thing that’s always important is starting antiepileptic drugs [AEDs]. With CAR T, the risk of grade 3/4 ICANS is much higher. We’ll usually put patients on a prophylactic. We use levetiracetam as our preferred AED. We’ll put them on prophylactically to prevent them from reaching this. At grade 3/4, which is where those seizures come in, those patients have a much lower risk compared with CAR Ts. We don’t put patients on prophylactic AEDs unless they start to see early signs of ICANS, which is that first decrease in the ICE [immune effector cell-associated encephalopathy] score or neurological symptoms. It’s good to get them on AEDs as soon as possible. We don’t wait until they have a seizure.
The other thing that’s really important is anakinra and how that differs from tocilizumab. Tocilizumab is focused on IL-6. Anakinra is focused on IL-1. That’s that other cytokine that can be elevated in these patients. It also has really good CNS penetration. Having that ability to help manage this neurological toxicity, in a drug that’s meant to specifically help with that CNS [central nervous system] penetration and management of that interleukin, is really important. Dexamethasone has good CNS penetration as well. It helps with the migration of white blood cells. You’ll start at that dose, but you may have to increase the dose if they’re not responding. You can see a big range of dosing. Even in grade 4 patients, you may have to go up to high-dose methylprednisolone at 2 mg/kg.
Ajai Chari, MD: You highlighted the importance of working with our consultants. Especially if the institution just starting with bispecifics and CAR Ts, it requires a systems approach. The neurologist has to start developing some familiarity with these toxicities. The neuroradiologist has to pick up the imaging changes, doing the EEGs [electroencephalograms] if patients aren’t improving. Another important pearl Robert alluded to was avoiding concurrent medications that might cause cognitive changes, which is why you’re picking a nonsedating antiepileptic drug. The other thing we’ve learned, which hasn’t come up in these patients, is tumor flare. Kiah, do you want to speak to tumor flares we’ve seen? Patients can get narcotics for that, but just so everyone is aware of what our experience has been.
Kiah Purcell, NP: Sometimes when patients receive these bispecific antibodies, because of the trafficking of the T cells, they’ll get increased pain at sites of disease. The last patient we discussed had extensive extramedullary disease. There are parts in her body with extramedullary disease. Even lytic lesions might have increased pain. There’s a chance we’re going to be giving larger doses of pain medication in that time, which could affect the neurological status, so there may be confusion from that. But these pain flares, these tumor flares, sometimes don’t respond to normal pain medication. In that case, we’ve also given dexamethasone for those incidences of tumor flare.
Ajai Chari, MD: Everything you said is 100% accurate. Radiation can also be used, especially if it’s concerning neurological paraspinal mask. It’s another good trick to have up our sleeves.
Transcript edited for clarity.
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