Dr Pan on Late-Onset Toxicities Associated With CAR T-Cell Therapy in Multiple Myeloma

"Between the delayed neurotoxicity and the delayed enterocolitis, those are likely the most significant toxicities, albeit rare. They are ones that we're trying to learn more about, both in terms of pathogenesis and clinical management. Hopefully, in the coming years, we will be better equipped to prevent and manage these AEs that we're seeing from CAR T-cell therapy"

Darren Pan, MD, assistant professor of Medicine at the University of California, San Francisco (UCSF) School of Medicine, described key late-onset toxicities associated with CAR T-cell therapies in patients with multiple myeloma.

Late-onset neurologic toxicities are among the most commonly observed delayed complications. These include cranial nerve palsies, Parkinsonism, and Guillain-Barré Syndrome, all of which have been reported in a minority of patients, Pan began. He noted that ongoing research at UCSF Health has identified older age as a potential risk factor for developing these delayed neurologic events following CAR T-cell therapy.

In addition to neurotoxicity, immune effector cell enterocolitis has emerged as a severe but rare complication, manifesting as inflammatory diarrhea that can occur several months after treatment, Pan continued. Although the incidence is low, the clinical significance of this toxicity, which may present with 5 or more episodes of diarrhea per day and lead to dehydration, malabsorption, and, in severe cases, the need for parenteral nutrition, Pan underscored. Some patients may experience life-threatening complications related to enterocolitis, he added.

Both delayed neurotoxicity and enterocolitis are areas of active investigation, particularly with regard to pathogenesis and optimal management strategies, Pan emphasized. As clinical experience with CAR T-cell therapy expands, understanding and mitigating these late toxicities remains a priority. Of investigational agents such as anitocabtagene autoleucel continue to demonstrate favorable toxicity profiles, they may offer a preferred option in patients at risk for these late adverse effects, Pan concluded.