TPO Receptor Agonist for CAR-T-Associated Persistent Cytopenia

TPO receptor agonist treatment for severe persistent cytopenia associated with anti-CD-19 chimeric antigen receptor T (CAR-T) therapy resulted in complete cytopenia remission among most patients. These findings were published in the Annals of Hematology.

CAR-T therapy is an effective treatment for diffuse large B cell lymphoma (DLBCL), however, prolonged cytopenia occurs in approximately 30% of patients. In this study, 93 patients were evaluated for persistent cytopenia 21 to 28 days after CAR-T infusion at the Tel Aviv Sourasky Medical Center between 2019 and 2021. Patients with severe persistent cytopenia, defined as absolute neutrophil count (ANC) less than 500/mL and/or platelet count (PLT) less than 20,000/mL, were given TPO receptor agonists.

The median patient age was 69.14 years (range, 19-85) and 4 and 2 patients had prolonged severe cytopenia following tisagenlecleucel and axicabtagene therapy, respectively.

Five of the 6 patients developed their neutropenia by day 6 after CAR-T infusion. Four patients had neutrophil recovery followed by a secondary neutropenia event occurring between days 10 to 30.

The patients received TPO receptor agonist therapy a median of 43 days (range, 21-55) after CAR-T infusion. Four patients received eltrombopag, 1 patient received romiplostim, and 1 patient started on romiplostim and was switched to eltrombopag.

Five of the patients had complete resolution at a median 27 days (range, 6-38) for PLT and 29 days (range, 7-61) for ANC. No relapses were observed.

One patient had a grade 1 increase in liver enzymes at 10 days, which resolved after 3 days of withholding therapy. No other toxicity events occurred.

This study was limited by its small sample size.

The study authors concluded that additional research into the efficacy and safety of TPO receptor agonist treatment for CAR-T-associated severe prolonged neutropenia in DLBCL is warranted.

Reference

Beyar-Katz O, Perry C, On YB, et al. Thrombopoietin receptor agonist for treating bone marrow aplasia following anti‑CD19 CAR‑T cells—single‑center experience. Ann Hematol. 2022;101:1769-1776. doi:10.1007/s00277-022-04889-6