'The HemOnc Pulse' Live 2024 in Chicago: CAR-T Unanswered Questions

“The HemOnc Pulse” goes on the road to Chicago May 3-4 with host Chadi Nabhan, MD, MBA, FACP, for the first live meeting.

This podcast episode features a panel discussion on unanswered questions in chimeric antigen receptor (CAR) T-cell therapy with Caron Jacobson, MD, MMSc, Medical Director of the Immune Effector Cell Therapy Program at the Dana-Farber Cancer Institute; Michael Bishop, MD, FACP, FASCO, Director of the Hematopoietic Stem Cell Transplantation Program at the University of Chicago; Joseph Mikhael, MD, MEd, FRCPC, FACP, a Professor in the Applied Cancer Research and Drug Discovery Division at the Translational Research Institute, an affiliate of the City of Hope Cancer Center; and Alan Skarbnik, MD, Director of the Lymphoma and Chronic Lymphocytic Leukemia Program and Director of Experimental Therapeutics, Malignant Hematology, at Novant Health.

The panelists focused on three unanswered questions:

• What are the major mechanisms of resistance?
• How can engineered cell therapies work (better) in solid tumors?
• How can allogeneic CAR T cells be improved?

“I don’t know if CAR T cells are the best path,” said Dr. Bishop on the topic of cellular therapeutics for solid tumors. “T-cell receptor (TCR)-modified cells, either T cells or natural killer cells, may be a more attractive platform…we have seen remarkable responses.”

The panel also discussed patient quality of life and the risk of secondary malignancies and other toxicities after CAR-T. “There’s still a toxicity issue we need to solve,” said Dr. Mikhael, outlining neurological toxicities such as Parkinsonian symptoms in patients with multiple myeloma after CAR-T.

“All the strategies to use CD52 antibodies, and knock out CD52 from the CAR or enhance leukodepletion, have been met with an increased risk of infection,” Dr. Jacobson added.

The conversation shifted toward how a patient’s geographical location and race may impact their access to CAR-T. “My most pressing question in CAR-T is how to improve access,” Dr. Skarbnik stated.

“Three things have moved the field of myeloma forward, and they happen to all start with the letter T: triplets, transplants, and trials,” said Dr. Mikhael. “We clearly, sadly, have demonstrated that there are always underrepresented populations in those three areas, particularly in the Black population where myeloma is twice as common. Now, we see a fourth T in CAR-T.”