Dr Phillips on the Management of Toxicities Associated With CAR T-Cell Therapy

Adrienne Phillips, MD, MPH, hematologist/oncologist, Director of Cell Therapy and Bone Marrow Transplantation Northern Regions, RWJBarnabas Health, associate professor, medicine, Rutgers Robert Wood Johnson Medical School, discusses the management of toxicities associated with CAR T-cell therapy across hematologic malignancies.

Treatment with CAR T-cell therapies leads to a distinct toxicity profile, Phillips begins. The most important adverse effects (AEs) for patients and their providers to be made aware of are cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), she states. Patients with CRS may present with fevers, hypoxia, hypotension, and tachycardia. In certain instances, low-grade CRS can progress and become more severe, Phillips details, stating that those with high-grade CRS may require closer monitoring and blood pressure support.

Initial ICANS events occasionally resulted in fatalities in early studies of CAR T-cell therapy, Phillips continues. However, mitigation strategies involving tocilizumab (Actemra) or prednisone have significantly reduced the incidence and severity of this AE, Phillips says. The success of current approaches to toxicity management combined with the demonstrated efficacy of CAR T-cell therapies across hematologic malignancies have supported efforts to explore the feasibility of CAR T-cell administration in an outpatient setting, Phillips notes.

Meanwhile, the biological understanding of CAR T-cell–associated toxicity is evolving with novel insights into how variation in co-stimulatory domains could potentially influences AEs, Phillips expands. For example, axicabtagene ciloleucel (Yescarta;axi-cel), which has a CD28 co-stimulatory domain, is considered more toxic than lisocabtagene maraleucel (Breyanzi; liso-cel), another approved CAR T-cell product using a different co-stimulatory domain, Phillips states. This variance in co-stimulatory domains prompts further exploration into its impact on toxicity, she explains.

Despite the challenges and limitations of CAR T-cell administration, ongoing research is refining the management of patients undergoing CAR T-cell therapy. Lessons learned from early research have led to the development of effective strategies, contributing to the increased safety of this transformative therapy, Phillips emphasizes. Overall, the potential ability to administer certain CAR T-cell products in outpatient settings underscores the progress made in mitigating toxicities associated with this treatment modality, Phillips concludes.