Severe cytopenia after CD19 CAR T-cell therapy: a retrospective study from the EBMT Transplant Complications Working Party
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Severe cytopenia after CD19 CAR T-cell therapy: a retrospective study from the EBMT Transplant Complications Working Party. / Penack, Olaf; Peczynski, Christophe; Koenecke, Christian; Polge, Emmanuelle; Kuhnl, Andrea; Fegueux, Nathalie; Daskalakis, Michael; Kröger, Nicolaus; Dreger, Peter; Besley, Caroline; Schanz, Urs; Bloor, Adrian; Ganser, Arnold; Forcade, Edouard; Corral, Lucia López; Passweg, Jakob R; Novak, Urban; Moiseev, Ivan; Schoemans, Hélène; Basak, Grzegorz W; Chabannon, Christian; Sureda, Anna; Averbuch, Dina; Glass, Bertram; de la Camara, Rafael; Peric, Zinaida.
in: J IMMUNOTHER CANCER, Jahrgang 11, Nr. 4, e006406, 04.2023.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Severe cytopenia after CD19 CAR T-cell therapy: a retrospective study from the EBMT Transplant Complications Working Party
AU - Penack, Olaf
AU - Peczynski, Christophe
AU - Koenecke, Christian
AU - Polge, Emmanuelle
AU - Kuhnl, Andrea
AU - Fegueux, Nathalie
AU - Daskalakis, Michael
AU - Kröger, Nicolaus
AU - Dreger, Peter
AU - Besley, Caroline
AU - Schanz, Urs
AU - Bloor, Adrian
AU - Ganser, Arnold
AU - Forcade, Edouard
AU - Corral, Lucia López
AU - Passweg, Jakob R
AU - Novak, Urban
AU - Moiseev, Ivan
AU - Schoemans, Hélène
AU - Basak, Grzegorz W
AU - Chabannon, Christian
AU - Sureda, Anna
AU - Averbuch, Dina
AU - Glass, Bertram
AU - de la Camara, Rafael
AU - Peric, Zinaida
N1 - © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2023/4
Y1 - 2023/4
N2 - We investigated the incidence and outcome of anti-CD19 chimeric antigen receptor (CAR) T-cells-associated Common Terminology Criteria for Adverse Events (CTCAE) ≥grade 3 cytopenia. In the EBMT CAR-T registry, we identified 398 adult patients with large B-cell lymphoma who had been treated with CAR-T-cells with axicel (62%) or tisacel (38%) before August 2021 and had cytopenia status documented for the first 100 days. Most patients had received two or three previous lines of therapy, however, 22.3% had received four or more. Disease status was progressive in 80.4%, stable in 5.0% and partial/complete remission in 14.6%. 25.9% of the patients had received a transplantation before. Median age was 61.4 years (min-max; IQR=18.7-81; (52.9-69.5)).The cumulative incidence of ≥grade 3 cytopenia was 9.0% at 30 days (95% CI (6.5 to 12.1)) and 12.1% at 100 days after CAR T-cell infusion (95% CI (9.1 to 15.5)). The median time from CAR-T infusion to cytopenia onset was 16.5 days (min-max; IQR=1-90; (4-29.8)). Grade 3 and grade 4 CTCAE cytopenia occurred in 15.2% and 84.8%, respectively. In 47.6% there was no resolution.Severe cytopenia had no significant impact on overall survival (OS) (HR 1.13 (95% CI 0.74 to 1.73), p=0.57). However, patients with severe cytopenia had a poorer progression-free survival (PFS) (HR 1.54 (95% CI 1.07 to 2.22), p=0.02) and a higher relapse incidence (HR 1.52 (95% CI 1.04 to 2.23), p=0.03). In those patients who developed severe cytopenia during the first 100 days (n=47), OS, PFS, relapse incidence and non-relapse mortality at 12 months after diagnosis of severe cytopenia were 53.6% (95% CI (40.3 to 71.2)), 20% (95% CI (10.4 to 38.6)), 73.5% (95% CI (55.2 to 85.2)) and 6.5% (95% CI (1.7 to 16.2)), respectively.In multivariate analysis of severe cytopenia risk factors, only year of CAR-T infusion (HR=0.61, 95% CI (0.39 to 0.95), p=0.028) and total number of treatment lines before CAR-T infusion (one or two lines vs three or more, HR=0.41, 95% CI (0.21 to 0.83), p=0.013) had a significant positive association with the incidence of cytopenia. Other factors, such as previous transplantation, disease status at time of CAR-T, patient age and patient sex, had no significant association.Our data provide insight on frequency and clinical relevance of severe cytopenia after CAR T-cell therapy in the European real-world setting.
AB - We investigated the incidence and outcome of anti-CD19 chimeric antigen receptor (CAR) T-cells-associated Common Terminology Criteria for Adverse Events (CTCAE) ≥grade 3 cytopenia. In the EBMT CAR-T registry, we identified 398 adult patients with large B-cell lymphoma who had been treated with CAR-T-cells with axicel (62%) or tisacel (38%) before August 2021 and had cytopenia status documented for the first 100 days. Most patients had received two or three previous lines of therapy, however, 22.3% had received four or more. Disease status was progressive in 80.4%, stable in 5.0% and partial/complete remission in 14.6%. 25.9% of the patients had received a transplantation before. Median age was 61.4 years (min-max; IQR=18.7-81; (52.9-69.5)).The cumulative incidence of ≥grade 3 cytopenia was 9.0% at 30 days (95% CI (6.5 to 12.1)) and 12.1% at 100 days after CAR T-cell infusion (95% CI (9.1 to 15.5)). The median time from CAR-T infusion to cytopenia onset was 16.5 days (min-max; IQR=1-90; (4-29.8)). Grade 3 and grade 4 CTCAE cytopenia occurred in 15.2% and 84.8%, respectively. In 47.6% there was no resolution.Severe cytopenia had no significant impact on overall survival (OS) (HR 1.13 (95% CI 0.74 to 1.73), p=0.57). However, patients with severe cytopenia had a poorer progression-free survival (PFS) (HR 1.54 (95% CI 1.07 to 2.22), p=0.02) and a higher relapse incidence (HR 1.52 (95% CI 1.04 to 2.23), p=0.03). In those patients who developed severe cytopenia during the first 100 days (n=47), OS, PFS, relapse incidence and non-relapse mortality at 12 months after diagnosis of severe cytopenia were 53.6% (95% CI (40.3 to 71.2)), 20% (95% CI (10.4 to 38.6)), 73.5% (95% CI (55.2 to 85.2)) and 6.5% (95% CI (1.7 to 16.2)), respectively.In multivariate analysis of severe cytopenia risk factors, only year of CAR-T infusion (HR=0.61, 95% CI (0.39 to 0.95), p=0.028) and total number of treatment lines before CAR-T infusion (one or two lines vs three or more, HR=0.41, 95% CI (0.21 to 0.83), p=0.013) had a significant positive association with the incidence of cytopenia. Other factors, such as previous transplantation, disease status at time of CAR-T, patient age and patient sex, had no significant association.Our data provide insight on frequency and clinical relevance of severe cytopenia after CAR T-cell therapy in the European real-world setting.
KW - Adult
KW - Humans
KW - Middle Aged
KW - Immunotherapy, Adoptive/adverse effects
KW - Receptors, Chimeric Antigen
KW - Retrospective Studies
KW - Neoplasm Recurrence, Local/etiology
KW - Anemia
KW - Antigens, CD19
U2 - 10.1136/jitc-2022-006406
DO - 10.1136/jitc-2022-006406
M3 - SCORING: Journal article
C2 - 37072350
VL - 11
JO - J IMMUNOTHER CANCER
JF - J IMMUNOTHER CANCER
SN - 2051-1426
IS - 4
M1 - e006406
ER -