Expert Point of View: Susan O'Brien, MD

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“Some people are disappointed in the results, but the problem is there was too much hype to begin with.”
— Susan O'Brien, MD

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Commenting on the studies of CAR T cells in chronic lymphocytic leukemia (CLL) thus far, Susan O’Brien, MD, of the University of California at Irvine, said: “Some people are disappointed in the results, but the problem is there was too much hype to begin with. The first article on CAR T published in The New England Journal of Medicine was on one patient.” 

“CAR T remains an innovative interesting treatment strategy,” Dr. O’Brien continued. “The results of Dr. Maloney’s study are impressive. All of these patients are extremely refractory to chemotherapy and to ibrutinib [Imbruvica], and they are very high risk, yet they are doing well on CAR T.” 

Steps to Improve Outcomes and Toxicity 

“The way forward to making this therapy more useful is to improve the side-effect profile. Perhaps one strategy might be to use tocilizumab (Actemra) earlier, before patients develop grade 2 or 3 cytokine-release syndrome. It is hard to advance this therapy when 25% have to go to the ICU with cytokine-release syndrome or neurotoxicity,” Dr. O’Brien acknowledged. 

“Older trials are not using the CD4/CD8 fixed ratio that Dr. Maloney’s group is studying. The fixed ratio CAR T cells may improve outcomes,” she said. 

That said, Dr. O’Brien pointed out that up until recently, all CLL regimens were T-cell–depleting. “A technology that relies on T cells is problematic, but with the use of oral small-molecule agents rather then chemotherapy, this problem may go away; however, we need to improve the safety profile of CAR T cells.” ■

DISCLOSURE: Dr. O’Brien reported no conflicts of interest. 

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