Safety of Cilta-Cel in Patients With R/R Multiple Myeloma

Jesus Berdeja, MD, director of myeloma research at Sarah Cannon Research Institute and hematology specialist at Tennessee Oncology, discusses the safety profile observed with the newly approved chimeric antigen receptor (CAR) T-cell therapy, ciltacabtagene autoleucel (cilta-cel; Carvykti), as observed in the phase 1/2 CARTITUDE-1 clincial trial (NCT03548207).

The FDA granted approval to the agent for the treatment of patients with relapsed/refractory multiple myeloma who have received 4 or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody on February 28, 2022.

Berdeja explains that the agent’s safety and tolerability is similar to other drugs in its class. Toxicities included some cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), but most cases were low grade.

Transcription:

0:08 | You know, in terms of safety, this was not too dissimilar from other CAR T cells in myeloma. So, the majority of patients etc, can rescind from most of those patients at grade 1, 2. Secondly, it's very manageable. Very few patients had grade 3 or 4 [toxicities]. And all those patients ultimately recovered, I can say, or the neurotoxicity associated with CAR T cells, was also very similar.

0:33 | With other CAR T products, the minority of patients had that toxicity. And again, mostly grade 1 and 2, usually associated, or in the setting of CRS. What was different with the study was that in a small subset of patients, there was a delayed neurotoxicity. That was seen the median, I think, of 27 days, so a little bit removed from the traditional CRS, and ICANS, which occurs about a weekend to CAR T cells. And this other neurotoxicity, that's the term that was used in the study, was manifested more with sort of motion, cognitive Parkinsonian type symptoms that are not usual for traditional ICANS that we see with CAR T cells. There were also some peripheral nerves and gamma ray type syndrome and some cranial nerve abnormalities. Again, this was a very small subset of patients. I believe, in total, the Parkinsonian syndromes were 5% of patients, but they were very high grade and there were some patients that never recovered, did not respond to therapy, and ultimately died with this neurotoxicity still occurring.

1:51 | So, I think the bottom line is, again, this is rare. It appears to be more common in patients who had high burden of disease who had had prior I can sense that it can release. So, in patients who fit those criteria, I think that need to be monitored, especially closely for the possibility of developing this later toxicity. The sort of with further studies in the CARTITUDE program as this was recognized, patients were treated to have their disease better controlled, patients who did develop cytokine release and ICANS actually had more aggressive control of their initial disease, and this has mitigated significantly the secondary or late neurotoxicity, but definitely worth knowing as this product goes to market and is being utilized more broadly.