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Tuesday, June 2, 2020

Durable Remission, Rare Adverse Effects With Anti-CD19 CAR-T Therapy in CLL, Lymphoma

By Veronica Hackethal

Anti-CD19 CAR T-cell therapy is associated with highly durable remissions in relapsed B-cell lymphoma and chronic lymphocytic leukemia (CLL), according to research presented at the 2020 ASCO Annual Meeting (Abstract 3012). The study has the longest follow-up to date on this topic, and reports long-term remissions lasting over 9 years in B-cell lymphoma.

"These long-term remissions raise the possibility, but do not prove that CAR T cells could be curative for some B-cell lymphomas, including diffuse large B-cell lymphoma, low-grade lymphomas, and CLL," first author Kathryn Cappell, MD, PhD, told Oncology Times. She is associated with the National Cancer Institute.

Notably, the study showed that long-term adverse effects with anti-CD19 CAR T cells were rare, manageable, and usually mild. B-cell depletion and low immunoglobulin levels represented the most common long-term adverse effects. Nine percent of participants developed infections requiring hospitalization 6 months or longer after receiving CAR T cells. Sixteen percent of patients developed second malignancies on long-term follow-up, according to Cappell.

"This rate of second malignancies is not higher than expected given that the patients in the study had extensive previous chemotherapy treatments before enrolling in this study," she said.

The study included 43 patients who received Anti-CD 19 CAR-T therapy between 2009 and 2015. Anti-CD19 CAR T cells is a genetically engineered treatment that uses the patient's own T cells to express synthetic chimeric antigen receptors (CARs) targeted against the CD19 antigen found on malignant and normal B lymphocytes.

Overall, 63 percent of participants had chemotherapy-refractory lymphoma. Before entering the study, they had undergone a median of four previous lines of therapy. Most had aggressive lymphoma (89%, 28 patients), while 20 percent had low-grade lymphoma (8 patients), and 25 percent had chronic lymphocytic leukemia (CLL, 7 patients).

The study treatment consisted of conditioning with cyclophosphamide plus fludarabine chemotherapy, followed by anti-CD19 CAR T-cell therapy. Researchers divided the cohort into three treatment groups which differed by the CAR T-cell production process and conditioning chemotherapy dose. The median CAR T-cell dose per kilogram was 2 x 106, which varied by cancer type (aggressive lymphoma: 2 x 106 ; low-grade lymphoma: 3 x 106 ; CLL: 3.5 x 106).

Three patients required re-treatment, and the analysis included 46 CAR T-cell treatments in total.

Results showed an overall remission rate (ORR) of 76 percent, of whom 54 percent had complete remission and 22 percent had partial remission. Participants who were able to achieve complete remission had significantly higher median peak blood levels of CAR T cells compared to those who did not reach complete remission (86 CAR+ cells/µL vs 16 CAR+ cells/µL, respectively, P= 0.0041).

Analyses excluding three patients who could not be evaluated for response showed an overall response rate of 81 percent, of whom 58 percent showed complete remission and 23 percent showed partial remission.

Veronica Hackethal is a contributing writer.