Dr Oluwole on the Use of CAR T-Cell Therapy in Autoimmune Disorders

Olalekan O. Oluwole, MBBS, MD, associate professor, medicine, hematology/oncology, Vanderbilt Institute for Infection, Immunology and Inflammation, Vanderbilt University Medical Center, discusses the feasibility of using CAR T-cell therapy for patients with nonhematologic autoimmune disorders.

In early clinical trials investigating CAR T-cell therapy for patients with lymphomas, patients with active autoimmune disorders did not experience favorable outcomes because the T cells that were harvested from these patients were autoreactive, Oluwole says. These T cells increased the incidence of on-treatment toxicities, including cytokine release syndrome, neurological adverse effects, and hemophagocytic lymphohistiocytosis, Oluwole notes.

However, the data from those early trials served as a foundation for further CAR T-cell research in patients with autoimmune disorders, Oluwole explains. Investigators have found several differences between autoimmune disorders and lymphoma, according to Oluwole. For instance, although patients with lymphoma require a high dose of CAR T cells, lower CAR T-cell doses are effective in patients with nonhematologic autoimmune disorders. They also cause fewer toxicities than those observed in studies of CAR T-cell therapy in patients with lymphoma and autoimmune disorders, Oluwole emphasizes.

Furthermore, CAR T-cell therapy has become a prevalent treatment approach across hematologic malignancies, including large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, and acute lymphoblastic leukemia, Oluwole says. As hematologists have gained experience using this therapy, they have learned how to mitigate associated toxicities. This is often achieved through close monitoring and early intervention, Oluwole notes. An increasing level of familiarity with administering CAR T-cell therapy to patients with hematologic malignancies has prompted the investigation of CAR T-cell products in patients with autoimmune disorders, Oluwole explains.

Patients with autoimmune disorders who have exhausted all standard treatment options are ideal candidates for enrolling in clinical trials evaluating immunotherapy for this disease, according to Oluwole. Patients for whom all available treatment options are ineffective or intolerable should be offered investigational treatment with bispecific antibodies, as well as autologous and allogeneic CAR T-cell therapies, Oluwole emphasizes. This research will help clinicians determine which therapies can best improve these patients’ quality of life and where these agents should be sequenced in the paradigm, Oluwole concludes.