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Chance or CAR-T: Expert Weighs in on FDA Investigation


An expert discusses the FDA’s investigation into the possible association between CAR-T cell therapy and secondary T-cell malignancies.

The sooner more data comes out about the potential association between CAR-T cell therapy and secondary T-cell malignancies the better, said Dr. John Lister.

“Right now, I don't think that (the recent Food and Drug Administration [FDA]) announcement is going to result in a complete halt of approval of any of these products, because, quite frankly, there aren't a lot of there aren't a lot of options,” Lister, who is the chief of Hematology and Cellular Therapy at the Allegheny Health Network Cancer Institute, said in an interview with CURE®.

infographic of KOL

On Nov. 28, the FDA announced that it was investigating “serious risk of T-cell malignancy following BCMA-directed or CD19-directed autologous chimeric antigen receptor (CAR)-T cell immunotherapies.” The agency announced that it had received reports of T-cell diseases, including certain types of lymphoma, in patients with blood cancer who were treated with CAR-T cell therapy.

READ MORE: Benefits Outweigh Risks as FDA Inspects CAR-T Cell Therapy-Related Cancer

Lister explained that patients with cancer tend to already have an increased risk of developing a secondary cancer, so while there is a chance that the CAR-T cell therapy or its manufacturing process could be a factor in these patients developing T-cell malignancies, it could also be simple chance.

What We Know About the CAR-T Cell Therapy News:

  • The FDA announced is investigating instances of T-cell malignancies, such as certain types of lymphoma, that occurred in a small number of patients who received BCMA- or CD19-directed CAR-T cell therapies.
  • Experts say that CAR-T cell therapy may still be the best treatment option for some patients, and the FDA said that the benefits outweigh potential risks.
  • Patients with B-cell malignancies have an increased risk of T-cell malignancies.
  • The FDA said that it is “evaluating the need for regulatory action.”

What Unanswered Questions Remain:

  • What is the rate or likelihood of patients who underwent CAR-T cell therapy who are later diagnosed with a B-cell malignancy?
  • What, exactly, is causing the T-cell malignancies to occur in patients who underwent CAR-T cell therapy?

“When it comes to CAR-T cell therapy, this has been one of the things that we're surveilling in all of the clinical trials that are being done and all the commercial products also — the question will be: is the process of making a CAR-T cell the thing that turned this the cell malignant? And does that T-cell malignancy come from, from cells that are modified by the CAR construct? We're not sure of that yet,” he said. “That being said, any patient with a B-cell malignancy also has an increased risk of getting a T-cell malignancy. So with the large application of CAR-T cell therapy across the globe, it may simply be that we're identifying patients who are at risk for getting T-cell malignancy anyway. So the molecular biology will have to be performed on those the specimens of the T cell malignancy to sort that out.”

Clinicians and researchers are now hard at work to answer those questions. Lister said that at his institution, when patients are treated with a CAR-T cell therapy, they are monitored for the rest of their life.

“The first thing we would be looking for would be any sign that the patient developed a malignancy that might be related to the manufacturing process for CAR-T cell therapy. That’s our No. 1 goal,” he said. “The second (goal) is to monitor for any other unforeseen events that may occur or that happens with a much greater frequency than it should for that cohort of patients.”

Based on the limited information that is currently available, Lister does not think that people should steer away from getting CAR-T cell therapy if it is the best available treatment option for their blood cancer.

“I don’t think that it would be reasonable for anybody to not entertain getting CAR-T cell therapy based upon the findings for now, but one should know that the FDA has been looking for these (secondary malignancies), as we all have,” he said. “We need to stay tuned as the FDA gets further reports and as more literature is published on these particular cases, and that’s certainly going to tell us more about the frequency with which it occurs.”

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