Expert Point of View: Edward A. Stadtmauer, MD

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The age of cellular immunotherapy for myeloma is upon us.
— Edward A. Stadtmauer, MD

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In a lecture at the 2016 American Society of Hematology (ASH) Annual Meeting & Exposition, Edward A. Stadtmauer, MD, Chief of the Hematologic Malignancies Section at the University of Pennsylvania Perelman School of Medicine, Philadelphia, summarized the advances in chimeric antigen receptor (CAR) T-cell therapy and announced, “The age of cellular immunotherapy for myeloma is upon us.” Anti-CD19 CAR T cells (CTL019) and anti–B-cell maturation antigen products are only two of many candidate antigen targets in this malignancy, he noted.

While the findings reported at the ASH meetings are positive, he believes there are ways to improve upon the current CAR T-cell constructs. Some ideas include initiating CAR T-cell therapy earlier in the disease, maximizing the persistence of modified T cells (such as with better lymphodepleting conditioning, higher dose intensity, or serial infusions), engineering the cells for greater potency, potentiating their activity with checkpoint inhibitors, administering cocktails of cells with multiple targets, and optimizing allogeneic “off-the-shelf” products.

“Remarkable clinical responses have been seen with B-cell maturation antigen and CD19 genetically modified T cells, but still only a minority of patients respond,” Dr. Stadtmauer commented. “Fortunately, cytokine-release syndrome, neurologic toxicity, graft-vs-host disease, and on-target/off-tumor toxicities have generally been limited in frequency, duration, and severity. But we still need to study approaches aimed at engineering these products for improved activity, persistence, and decreased toxicity.” ■

Disclosure: Dr. Stadtmauer has been a consultant for Amgen, Takeda, Celgene, Novartis, and Janssen.

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