Early-Phase Results With CD19-Directed Immunotherapy for CLL
Posted: Friday, January 17, 2020
Lisocabtagene maraleucel, an investigational, anti–CD19-directed chimeric antigen receptor (CAR) T-cell product, produced manageable toxicity and durable responses in patients with heavily pretreated chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia. Tanya Siddiqi, MD, of the City of Hope National Medical Center in Duarte, California, presented these results from the TRANSCEND CLL 004 trial on behalf of her colleagues at the 2019 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 503).
This open-label phase I/II study enrolled 23 patients with CLL or small lymphocytic leukemia who had received a minimum of 2 or 3 prior lines of therapy if they had high- or normal-risk disease, respectively. Patients completed 3 days of lymphodepletion with fludarabine/cyclophosphamide before being administered a lisocabtagene maraleucel infusion. Researchers tested two dose levels: 50 x 106 and 100 x 106 CAR T cells.
At the time of data cutoff, lisocabtagene maraleucel was successfully manufactured in 96% of patients. Nine of these patients received the lower dose level and 14 received the higher dose level. Among patients evaluable for response, the best overall response rate was 82%. By day 30, 68% of patients had achieved an objective response, and 78% of patients who responded to treatment remained free of disease progression at 9 months of follow-up. For six patients, their responses reportedly deepened over time. Among the 20 patients who were evaluable for minimal residual disease, most achieved blood and/or bone marrow–undetectable minimal residual disease. All of these patients retained undetectable minimal residual disease at the time of the presentation.
Common grade 3 or 4 adverse events included thrombocytopenia, anemia, neutropenia, and leukopenia. In addition, two patients experienced grade 3 cytokine-release syndrome, and five had grade 3 or greater neurologic events. Lymph node tumor burden was associated with the development of neurologic events.
Disclosure: For full disclosures of the study authors, visit ash.confex.com.