Thrombopoietin receptor agonist for treating bone marrow aplasia following anti-CD19 CAR-T cells-single-center experience.
Adult
Aged
Anemia, Aplastic
/ drug therapy
Antigens, CD19
Bone Marrow
/ pathology
Hematologic Agents
/ therapeutic use
Humans
Lymphoma, Large B-Cell, Diffuse
/ pathology
Receptors, Chimeric Antigen
Receptors, Thrombopoietin
/ agonists
T-Lymphocytes
Thrombocytopenia
/ chemically induced
Thrombopoietin
/ adverse effects
CAR-T cells
Lymphoma
TPO agonists
Journal
Annals of hematology
ISSN: 1432-0584
Titre abrégé: Ann Hematol
Pays: Germany
ID NLM: 9107334
Informations de publication
Date de publication:
Aug 2022
Aug 2022
Historique:
received:
09
02
2022
accepted:
01
06
2022
pubmed:
23
6
2022
medline:
16
7
2022
entrez:
22
6
2022
Statut:
ppublish
Résumé
Anti CD-19 chimeric antigen receptor T (CAR-T) cells demonstrate effective early anti-tumor response; however, impaired hematopoietic recovery is observed in about 30% of patients with prolonged cytopenia appearing as an unmet need for optimal treatment. All adult patients given commercially available anti CD-19 CAR-T for diffuse large B cell lymphoma (DLBCL) were screened at 21-28 days after CAR-T infusion for cytopenia. In case of severe persistent cytopenia, patients were given TPO receptor agonists. Initial dose of eltrombopag was 50 mg/day and gradually increased to a maximal dose of 150 mg/day. Romiplostim was given as subcutaneous injection once a week for 2 doses (125 mcg). Response was defined as transfusion independency along with resolution of severe neutropenia (ANC > 500 /microL) and/or platelets > 20,000/microL for three consecutive values on different days. TPO receptor agonists were tapered down when response was met. From May 2019 to December 2021, 93 patients were eligible (74%, tisagenlecleucel and 26%, axicabtagene ciloleucel). The median age was 69 (range, 19-85) years. Six patients (6.5%) (tisagenlecleucel, n = 4 or axicabtagene ciloleucel, n = 2) demonstrated prolonged severe cytopenia and were treated with TPO receptor agonists (eltrombopag, n = 4; romiplastim, n = 1, both drugs, n = 1). Median time from CAR-T infusion to initiation of TPO receptor agonist was 43 (range, 21-55) days. All patients were transfusion-dependent and were given daily GCSF prior to TPO receptor agonist administration. Response to TPO receptor agonists was seen in all 6 patients. Median time from TPO receptor agonist initiation to resolution of cytopenia was 22 (range, 8-124) days for Hb, 27 (range, 6-38) days for platelets, and 29 (range, 7-61) days for neutrophils. A complete resolution of all blood counts (ANC > 500 /microL and platelets > 20,000/microL and hemoglobin > 8 gr/dL) was seen in 5/6 patients. No toxicity was observed during the therapy course. This paper supports further investigation of TPO receptor agonists in the treatment of persistent cytopenia following CAR-T cell therapy.
Identifiants
pubmed: 35731278
doi: 10.1007/s00277-022-04889-6
pii: 10.1007/s00277-022-04889-6
doi:
Substances chimiques
Antigens, CD19
0
Hematologic Agents
0
Receptors, Chimeric Antigen
0
Receptors, Thrombopoietin
0
Thrombopoietin
9014-42-0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1769-1776Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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