Unmet Needs for Managing CRS and ICANS Due to CAR T-Cell Therapy

Nicolas Gazeau, MS, postdoctoral research scholar at Fred Hutchinson Cancer Center, discusses next steps and unmet needs following a positive retrospective study of anakinra (Kineret) for the management of neurotoxicity and cytokine release syndrome (CRS) in patients who received chimeric antigen receptor (CAR) T-cell therapy.

Investigators are looking at drugs for managing immune effector cell–associated neurotoxicity syndrome (ICANS) and CRS, which are potentially dangerous adverse events (AEs) associated with CAR T-cell therapy. This retrospective study of 43 patients who received CAR T-cell therapy showed faster recovery from CRS and ICANS and lower non-relapse mortality for those who received a higher dose—8 mg/kg per day—of anakinra. Antitumor response to the CAR T-cell therapy was also improved in this group.

Gazeau says there is a need for a randomized prospective study of anakinra to confirm these results so it can be approved by the FDA to manage CRS/ICANS, and a study [NCT04359784] is in progress at his institution. In general, more research is needed on the causes of CRS and ICANS to determine how CAR T-cells can maintain their efficacy without having serious AEs.

Besides corticosteroids, tocilizumab (Actemra) has been shown to be effective for CRS but not ICANS, and more options are needed.

TRANSCRIPTION:

0:08 | If we have a patient with refractory ICANS of CRS with a lot of steroids, we can think about anakinra as a treatment. If we use anakinra in the clinic, it is probably more relevant to use it with a high dose. We have to wait for sure to get the FDA approval for the treatment [with a] prospective study. Those prospective studies are ongoing.

We need prospective studies with a control group to prove if our patients have the benefits of this treatment. We have to think more about the CAR T-cell construct to keep the good efficacy of CAR T cell and try to avoid the AEs. We have to find another way to manage these toxicities. There are steroids. There is tocilizumab and now, maybe anakinra. There are also molecules that can could be interesting. We have to proceed with that for sure.