Background and Importance Impaired haematopoietic recovery is observed in about 30–50% of patients treated with anti-CD19 CAR-T cells, with prolonged cytopenia appearing as an unmet need for optimal treatment. Generally, treatment consists in the use of erythropoietin and G-CSF (Granulocyte Colony Stimulating Factor). Thrompopoietyn receptor agonists (TPOa) can be on option too, on the basis of their consolidated use in refractory poor graft function, following allogeneic stem cell transplantation and aplastic anaemia.
Aim and Objectives We present a 72 year old patient who received commercial tisagenlecleucel treatment for a diffuse large B-cell lymphoma (DLBCL) in July 2021. Complete molecular response at one month from infusion was obtained but persistent cytopenia was developed, requiring transfusional support.
Material and Methods At 28 days from CAR-T infusion, the patient showed pancytopenia, which persisted in the following months and required transfusions of both platelets and erythrocytes. No clinical response to erythropoietin nor G-CSF was obtained. In March 2022, bone marrow examination allowed to exclude the myelodysplastic syndrome diagnosis and showed relative myeloid hyperplasia and altered distribution of megakaryocytes. In June 2022, the patient was receiving monthly transfusion of erythrocytes and fortnightly transfusion of platelet, despite supportive care. Complete molecular response of lymphoma was confirmed. Treatment with eltrombopag was started at 50 mg/day.
Results Haematologic recovery was progressively obtained, achieving independence from transfusion as 40 days since starting the eltrombopag therapy; treatment with erythropoietin was stopped at 60 days and the G-CSF administration frequency was progressively reduced to 1 G-CSF dose per week. Eltrombopag dose was maintained at 50 mg/day, with no side effects.
Conclusion and Relevance The mechanism for late-onset cytopenia following CAR-T cells is still not clear, but it could be related to the sustained role of cytokines secreted by CAR-T cells during their expansion phase and during the following persistence phase. A series of 6 patients treated with eltrombopag and one patient treated with romiplostim are reported, with positive results in terms of haematological recovery. Although, further data on the role of TPOa in post-CAR-T bone marrow toxicity are needed as a few reports are available.
Ofrat Beyar-Katz et al. Annals of Hematology 2022;101:1769–1776.
Conflict of Interest No conflict of interest
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