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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, Vol. 11, No. 4, e006406, 04.2023.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Penack, O, Peczynski, C, Koenecke, C, Polge, E, Kuhnl, A, Fegueux, N, Daskalakis, M, Kröger, N, Dreger, P, Besley, C, Schanz, U, Bloor, A, Ganser, A, Forcade, E, Corral, LL, Passweg, JR, Novak, U, Moiseev, I, Schoemans, H, Basak, GW, Chabannon, C, Sureda, A, Averbuch, D, Glass, B, de la Camara, R & Peric, Z 2023, 'Severe cytopenia after CD19 CAR T-cell therapy: a retrospective study from the EBMT Transplant Complications Working Party', J IMMUNOTHER CANCER, vol. 11, no. 4, e006406. https://doi.org/10.1136/jitc-2022-006406

APA

Penack, O., Peczynski, C., Koenecke, C., Polge, E., Kuhnl, A., Fegueux, N., Daskalakis, M., Kröger, N., Dreger, P., Besley, C., Schanz, U., Bloor, A., Ganser, A., Forcade, E., Corral, L. L., Passweg, J. R., Novak, U., Moiseev, I., Schoemans, H., ... Peric, Z. (2023). Severe cytopenia after CD19 CAR T-cell therapy: a retrospective study from the EBMT Transplant Complications Working Party. J IMMUNOTHER CANCER, 11(4), [e006406]. https://doi.org/10.1136/jitc-2022-006406

Vancouver

Penack O, Peczynski C, Koenecke C, Polge E, Kuhnl A, Fegueux N et al. Severe cytopenia after CD19 CAR T-cell therapy: a retrospective study from the EBMT Transplant Complications Working Party. J IMMUNOTHER CANCER. 2023 Apr;11(4). e006406. https://doi.org/10.1136/jitc-2022-006406

Bibtex

@article{0e155b7c8539464181e023b63bb5460b,
title = "Severe cytopenia after CD19 CAR T-cell therapy: a retrospective study from the EBMT Transplant Complications Working Party",
abstract = "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.",
keywords = "Adult, Humans, Middle Aged, Immunotherapy, Adoptive/adverse effects, Receptors, Chimeric Antigen, Retrospective Studies, Neoplasm Recurrence, Local/etiology, Anemia, Antigens, CD19",
author = "Olaf Penack and Christophe Peczynski and Christian Koenecke and Emmanuelle Polge and Andrea Kuhnl and Nathalie Fegueux and Michael Daskalakis and Nicolaus Kr{\"o}ger and Peter Dreger and Caroline Besley and Urs Schanz and Adrian Bloor and Arnold Ganser and Edouard Forcade and Corral, {Lucia L{\'o}pez} and Passweg, {Jakob R} and Urban Novak and Ivan Moiseev and H{\'e}l{\`e}ne Schoemans and Basak, {Grzegorz W} and Christian Chabannon and Anna Sureda and Dina Averbuch and Bertram Glass and {de la Camara}, Rafael and Zinaida Peric",
note = "{\textcopyright} 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.",
year = "2023",
month = apr,
doi = "10.1136/jitc-2022-006406",
language = "English",
volume = "11",
journal = "J IMMUNOTHER CANCER",
issn = "2051-1426",
publisher = "BioMed Central Ltd.",
number = "4",

}

RIS

TY - JOUR

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 -