Dr Callander on the Management of CAR T-Cell Therapy–Associated Complications in Myeloma

“We have a lot more to learn about how to apply CAR T-cell therapies, how to pick the patients who are going to best benefit from them, and [how to] minimize complications.”

Natalie Callander, MD, a professor in the Division of Hematology, Medical Oncology, and Palliative Care in the Department of Medicine at the University of Wisconsin (UW) School of Medicine and Public Health; as well as the director of the Myeloma Clinical Program at the UW Carbone Cancer Center, discussed the evolving and controversial role of absolute lymphocyte count (ALC) monitoring in the treatment of patients with relapsed/refractory multiple myeloma following CAR T-cell therapy.

There is clinical concern regarding late-stage complications associated with CAR T-cell therapy, which, although occurring in a relatively small subset of patients, present significant management challenges, Callander began. She highlighted the emergence of late neurological complications, such as movement disorders that clinically resemble Parkinson’s disease. These conditions are concerning because the medical community currently lacks effective treatment strategies to address them once they manifest, she stated.

Research has shown a connection between elevated ALC levels and these late-onset complications, according to Callander. Although this recognition is a critical step forward for the field, Callander explained that the optimal clinical response to elevated ALC levels remains a subject of debate among experts. For instance, during a workshop hosted by OncLive® and CoMMit, hematologists debated various interventions, such as the use of steroids like dexamethasone, she said, noting that other experts held more skeptical views regarding the value of such treatments.

In addition to steroid use, Callander reported that the early administration of low-dose cyclophosphamide, delivered either orally or intravenously, might mitigate future CAR T-cell therapy–associated complications. Despite these efforts, Callander emphasized that the field is still trying to determine the most effective protocols for managing these risks. Furthermore, the relationship between CAR T-cell expansion and patient outcomes remains complex; although one might assume that greater expansion leads to better progression-free survival outcomes, retrospective analyses have yielded mixed results, she added. Callander concluded that these uncertainties underscore the urgent need for further research to better identify patients who will benefit most from CAR T-cell therapy and simultaneously minimize the risk of severe, long-term complications.