COLUMBUS, Ohio – A global study in which researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) played a lead role shows the effectiveness of chimeric antigen receptor (CAR) T-cell therapy in treating patients with Richter transformation (RT), a blood cancer with poor prognosis and no standard therapies. RT occurs when another blood cancer, chronic lymphocytic leukemia (CLL), transforms into an aggressive form of lymphoma, most commonly large B-cell lymphoma (LBCL). Although there is no standard of care for RT, treatment is usually modeled after LBCL therapy, but the median overall survival rate after RT diagnosis ranges from three months to a year – indicating a need for new treatments to improve patient outcomes. David Bond, MD, hematologist with the OSUCCC – James and assistant professor of hematology at The Ohio State University College of Medicine, was co-first author of this new study published in the Journal of Clinical Oncology. The study involved 12 cancer centers from around the world and sought to characterize the safety and effectiveness of anti-CD19 CAR T-cell therapy for patients with RT. CAR T-cell therapy involves removing a patient’s T cells, modifying them in a laboratory to boost their ability to kill cancer cells, and returning them to the patient. This therapy, which typically targets a protein called CD19 that plays a large role in B-cell cancers, has revolutionized cellular immunotherapy for patients with B-cell malignancies. Patients with RT are immunologically distinct due to the underlying CLL and have been excluded from many of the previous clinical trials that led to FDA approval of CAR T-cell therapy.  “Given that data are very limited regarding the utility of CAR T-cell therapy in patients with RT, we sought to explore it as a therapeutic option in this retrospective study,” said Bond, adding that the new study involved 69 patients with a median age of 64 who had undergone a median of four previous lines of therapy for CLL or RT before receiving CAR T-cell therapy. The researchers reported that the overall response rate to CAR T-cell therapy was 63%, with 46% of patients attaining a complete response. After a follow-up of 24 months, the median progression-free survival was 4.7 months. They also reported that the median overall survival was 8.5 months, and the two-year survival was 38%. Among patients achieving a complete response, the median duration of response was 27.6 months. “In summary,” the researchers stated, “this representative (patient) cohort demonstrates the feasibility and efficacy of CAR T-cell therapy for a very challenging-to-treat disease. Additional work is needed to optimize patient selection, bridging therapy and post-CAR T-cell maintenance therapy to enhance efficacy and reduce toxicity.”  As with CAR T-cell therapy in patients with LBCL, they wrote, infection was the major cause of non-relapse mortality among patients in this study, demonstrating a need to implement rigorous anti-infective measures.  “Overall, our data support the continued exploration of CAR T-cell therapy for RT through future clinical trials and use of CAR T-cell therapy for RT where commercially available,” said Bond. Other Ohio State or OSUCCC – James scientists who were co-authors on the study were Ying Huang; Seema Bhat, MD; Kerry Rogers, MD; Cecelia Miller, PhD; and Jennifer Woyach, MD. To learn more about cancer treatment and clinical trials at the OSUCCC – James, visit cancer.osu.edu or call 1-800-293-5066. ### Media Contact: Mary Ellen Fiorino, Mary.Fiorino@osumc.edu