Dr. Mikhael on Unanswered Questions in CAR-T

At the first annual “The HemOnc Pulse” Live meeting in Chicago, Illinois, Chadi Nabhan, MD, MBA, FACP, spoke with Joseph Mikhael, MD, of the Translational Genomics Research Institute in Phoenix, Arizona. They discussed the meeting’s session on unanswered questions in chimeric antigen receptor (CAR) T-cell therapy.

Although there are many unsolved issues in this field, Dr. Mikhael was pleased that the questions during the session fell into two clear camps. There were excellent questions of a scientific nature about CAR-T, including mechanism of resistance, applicability to solid tumors, and the feasibility of allogeneic CAR-T.

“But what I also loved is we had the real practical side of it. How are we going to increase access to CAR-T? How are we going to introduce it earlier in the disease course in multiple diseases?” Dr. Mikhael added.

How to use CAR-T in earlier lines of therapy, sequence it with bispecifics, and address longer-term toxicities are among such unanswered practical questions.

On the topic of secondary malignancies raised during the session, Drs. Nabhan and Mikhael agreed there is a dilemma of weighing competing risks when using CAR-T.

“Our oldest adage is ‘above all, do no harm.’ I never want to introduce anything that could harm my patient. On the other hand, it’s all a question of balance,” Dr. Mikhael explained.

Illustrating this point, he noted that CAR-T has benefited his patients who were at risk of imminent mortality from their disease, and such diseases carry their own risk of malignancy apart from CAR-T. However, more needs to be learned about the incremental risk associated with CAR-T.

“That incremental risk becomes important, and I think we’ll have a better handle on it in the years to come,” Dr. Mikhael said.