Updates in Prevention, Treatment of Cytokine Release Syndrome, Neurologic Toxicities for Patients With Multiple Myeloma

Pharmacy Times interviewed Craig Freyer, PharmD, BCOP, a clinical pharmacy specialist at Penn Medicine in the University of Pennsylvania Health System, and Andrew Lin, PharmD, BCOP, an oncology pharmacy specialist at Memorial Sloan-Kettering Cancer Center, to discuss their presentation at the recent ATOPP 2021 summit on re-examining the why, who, and where of chimeric antigen receptor T-cell (CAR T) therapy.

Alana Hippensteele: What are some important updates around the prevention and treatment of cytokine release syndrome and neurologic toxicities?

Andrew Lin: So, we know that these are the 2 most important toxicities after CAR T-cell therapy. They're the most common and the most important to consider because they add the most to the morbidity and mortality of the patients who receive these therapies.

I think the data that we presented at the conference would suggest that with preemptive and prophylactic tocilizumab, that early tocilizumab is really the way to go. I think many of the investigational protocols that are ongoing tend to be on the conservative side and try to hold off on giving tocilizumab unless they have a greater than grade 3 toxicity for the cytokine release syndrome (CRS). The data that we presented from the studies in our presentation would suggest that you should probably consider moving that up earlier, and I think that's a very reasonable change.

Also, ZUMA-1 data showed that earlier corticosteroids introduction doesn't compromise CAR T kinetics or efficacy, but more recent data that was recently published just this year does show that there is an effect on early steroid use and a high cumulative dose of corticosteroids.

I think clinically, that leaves us thinking that with steroids, if we have to use them, we should use them, but we should use as little as we can for as short a duration as we can and try to hold off on the early period of time.

The other approaches that we discussed in our presentation, like modifying the construction of the CAR T cells or adding on a pharmacologic on/off switch, those are all things that are interesting, and they're potentially coming down the pathway. They've shown some utility in refractory cases like with ruxolitinib or anakinra.

But I think what we should take away from our talk is that there is definitely a role for building some of these into the treatment pathway for refractory cases. So, tocilizumab for refractory CRS and then anakinra for refractory CRS and immune effector cell–associated neurotoxicity syndrome would both be reasonable options given the current data.