As reported in the Journal of Clinical Oncology by Cappell et al, long-term follow-up of a National Cancer Institute phase I trial has shown that anti-CD19 chimeric antigen receptor (CAR) T-cell therapy for various relapsed B-cell malignancies produced responses lasting 3 years or longer in half of treatments.
Study Details
The study involved 46 CAR T-cell treatments given to 43 patients between 2009 and 2015. Patients had diffuse large B-cell lymphoma or primary mediastinal B-cell lymphoma (n = 28), low-grade B-cell lymphoma (n = 8), or chronic lymphocytic leukemia (CLL; n = 7). The CAR used was FMC63-28Z, the same CAR used in axicabtagene ciloleucel. Conditioning with cyclophosphamide plus fludarabine was given prior to CAR T-cell treatment. The median number of prior lines of treatment among all patients was four (range = 1–12).
Key Findings
Among all patients, the median follow-up was 42 months (range = 1–123 months).
The percentages of CAR T-cell treatments resulting in > 3-year duration of response were 51% among 41 evaluable treatments, 48% for diffuse large B-cell lymphoma or primary mediastinal B-cell lymphoma, 63% for low-grade lymphoma, and 50% for CLL.
KEY POINTS
- The percentages of CAR T-cell treatments resulting in > 3-year duration of response were 51% among 41 evaluable treatments, 48% for diffuse large B-cell lymphoma or primary mediastinal B-cell lymphoma, 63% for low-grade lymphoma, and 50% for CLL.
- Long-term adverse effects were rare, apart from B-cell depletion and hypogammaglobulinemia.
A total of 58% of 43 total evaluable treatments resulted in best response of complete remission, and 23% resulted in best response of partial remission. Median duration of ongoing responses was 60 months, with a range of 14 to 113 months.
Median event-free survival of all 45 evaluable treatments was 55 months.
Median peak blood CAR-positive cell levels were higher among patients with response duration of longer than 3 years (98/mL, range = 9–1,217/mL) than among patients with response duration of shorter than 3 years (18/mL, range = 0–308/mL; P = .0051).
Long-term adverse effects were rare, apart from B-cell depletion and hypogammaglobulinemia. Among the 43 patients, 5 developed a nonhematologic malignancy after protocol treatment and 2 developed myelodysplastic syndrome.
The investigators concluded, “Complete remissions of a variety of B-cell malignancies lasting 3 or more years occurred after 51% of evaluable anti-CD19 CAR T-cell treatments. Remissions of up to 9 years are ongoing. Late adverse events were rare.”
James N. Kochenderfer, MD, of the National Institutes of Health, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by NCI intramural funding and a research agreement between NCI and Kite, a Gilead Company. For full disclosures of the study authors, visit ascopubs.org.
