MM’s Vulnerability to CAR T Was a Happy Surprise: Nikhil C. Munshi, MD

What has surprised Nikhil C. Munshi, MD, most about chimeric antigen receptor (CAR) T-cell therapy and other immune-based approaches to treat multiple myeloma (MM) is how vulnerable myeloma cells are to aggressive immune treatments.

Munshi, the director of basic and correlative science at the Jerome Lipper Multiple Myeloma Center, professor of medicine at Harvard Medical School/Dana-Farber Cancer Institute, and member of the IMF Scientific Advisory Board, has spent his career studying myeloma as an immune-based disease, asking how the immune system can be co-opted to fight it. Even so, he said, the speed of response has been a happy surprise. Myeloma that has progressed through 5, 6, or 7 lines of therapy and become resistant to every available myeloma drug can be eliminated by a single infusion of CAR T cells in about 2 weeks. Expecting that is one thing, he noted, but seeing it and being part of it has been biologically extraordinary.

Munshi stressed that CAR T cells function as a drug and that the function of the T cells used to make them is what matters. Preserving T-cell function by avoiding too many treatments that impair it is therefore important for these therapies to work as well as hoped. The same principle applies to bispecific antibodies, which he called cousins of CAR T cells: they depend on healthy immune cells in the patient’s body, so researchers study the immune system’s state to predict the best outcomes.

Immune cells, he explained, are part of the myeloma ecosystem. Invoking the old see-and-soil theory, he said that poisoning the soil can kill the seed, and he expects the next generation of treatment to target the tumor cells’ entire environment. Ultimately, CAR T cells show what the immune system can do that drugs cannot: recognize cancer, expand, and even adapt to keep fighting after treatment has been given. Munshi called that adaptability the immune system’s great strength.