Expert Point of View: Steven M. Devine, MD

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Response rates are high but so are relapse rates. CAR T-cell therapy may ultimately be better applied in patients with persistent minimal residual disease.
— Steven M. Devine, MD

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Formal discussant of these trials Steven M. Devine, MD, of The Ohio State University Comprehensive Cancer Center, Columbus, was not able to attend the ASCO Meeting, but his slides were presented to the audience. “CAR T-cell therapy was first thought of in the 1980s, but it is only recently that we have seen such amazing success,” according to Dr. Devine. “There are at least 48 trials in the United States and also trials in Europe, Asia, and Australia.”

‘A Good Idea’, But Questions Remain

“Fractionated dosing is a good idea. It maintained efficacy and reduced toxicity. We noted sepsis along with the three deaths from cytokine-release syndrome,” wrote Dr. Devine. However, he mentioned that questions remain for several reasons: Data were still limited on treating older less healthy patients; efficacy was amazing, but toxicity was high; and toxicity would limit the application of CAR T-cell therapy in patients with multiple comorbidities.

“Disease burden may determine toxicity, which suggests it may be time to move this therapy upfront earlier in the course of disease,” Dr. Devine wrote. “Response rates are high but so are relapse rates. CAR T-cell therapy may ultimately be better applied in patients with persistent minimal residual disease,” he continued.

In addition, the optimal lymphodepleting regimen needs to be defined. It is also not clear whether patients who have not had transplant but respond to CAR T-cell therapy should go on to transplant.

Unresolved Issues

According to Dr. Devine, several unresolved issues remain, including the optimal CAR construct, the optimal phenotype of T cells for transduction and infusion, and the best source of CAR T-cell therapy.

Issues for the global community that need to be resolved include a clear definition of cytokine-release syndrome, a better understanding of neurologic toxicity, cost, and regulatory hurdles. ■

Disclosure: Dr. Devine has received research funding from Genzyme.

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