Transfusion needs after CAR T-cell therapy for large B-cell lymphoma: predictive factors and outcome (a DESCAR-T study)

•More than half of the patients need transfusion support after CAR T-cell therapy; various factors may affect transfusion needs.•Transfused patients have a poorer outcome with both an increased lymphoma-related mortality and nonrelapse mortality. [Display omitted] Chimeric antigen receptor (CAR) T-c...

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Veröffentlicht in:Blood advances 2024-03, Vol.8 (6), p.1573-1585
Hauptverfasser: Vic, Samuel, Thibert, Jean-Baptiste, Bachy, Emmanuel, Cartron, Guillaume, Gastinne, Thomas, Morschhauser, Franck, Le Bras, Fabien, Bouabdallah, Kamal, Despas, Fabien, Bay, Jacques-Olivier, Rubio, Marie-Thérèse, Mohty, Mohamad, Casasnovas, Olivier, Choquet, Sylvain, Castilla-Llorente, Cristina, Guidez, Stéphanie, Loschi, Michaël, Guffroy, Blandine, Carras, Sylvain, Drieu La Rochelle, Laurianne, Guillet, Mathilde, Houot, Roch
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container_end_page 1585
container_issue 6
container_start_page 1573
container_title Blood advances
container_volume 8
creator Vic, Samuel
Thibert, Jean-Baptiste
Bachy, Emmanuel
Cartron, Guillaume
Gastinne, Thomas
Morschhauser, Franck
Le Bras, Fabien
Bouabdallah, Kamal
Despas, Fabien
Bay, Jacques-Olivier
Rubio, Marie-Thérèse
Mohty, Mohamad
Casasnovas, Olivier
Choquet, Sylvain
Castilla-Llorente, Cristina
Guidez, Stéphanie
Loschi, Michaël
Guffroy, Blandine
Carras, Sylvain
Drieu La Rochelle, Laurianne
Guillet, Mathilde
Houot, Roch
description •More than half of the patients need transfusion support after CAR T-cell therapy; various factors may affect transfusion needs.•Transfused patients have a poorer outcome with both an increased lymphoma-related mortality and nonrelapse mortality. [Display omitted] Chimeric antigen receptor (CAR) T-cells targeting CD19 have been approved for the treatment of relapse/refractory large B-cell lymphoma. Hematotoxicity is the most frequent CAR T-cell–related adverse event. Transfusion support is a surrogate marker of severe cytopenias. Transfusion affects patients’ quality of life, presents specific toxicities, and is known to affect immunity through the so-called transfusion-related immunomodulation that may affect CAR T-cell efficacy. We analyzed data from 671 patients from the French DESCAR-T registry for whom exhaustive transfusion data were available. Overall, 401 (59.8%) and 378 (56.3%) patients received transfusion in the 6-month period before and after CAR T-cell infusion, respectively. The number of patients receiving transfusion and the mean number of transfused products increased during the 6-month period before CAR T-cell infusion, peaked during the first month after infusion (early phase), and decreased over time. Predictive factors for transfusion at the early phase were age >60 years, ECOG PS ≥2, treatment with axicabtagene ciloleucel, pre–CAR T-cell transfusions, and CAR-HEMATOTOX score ≥2. Predictive factors for late transfusion (between 1 and 6 months after infusion) were pre–CAR T-cell transfusions, CAR-HEMATOTOX score ≥2, ICANS ≥3 (for red blood cells [RBC] transfusion), and tocilizumab use (for platelets transfusion). Early transfusions and late platelets (but not RBC) transfusions were associated with a shorter progression-free survival and overall survival. Lymphoma-related mortality and nonrelapse mortality were both increased in the transfused population. Our data shed light on the mechanisms of early and late cytopenia and on the potential impact of transfusions on CAR T-cell efficacy and toxicity.
doi_str_mv 10.1182/bloodadvances.2023011727
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[Display omitted] Chimeric antigen receptor (CAR) T-cells targeting CD19 have been approved for the treatment of relapse/refractory large B-cell lymphoma. Hematotoxicity is the most frequent CAR T-cell–related adverse event. Transfusion support is a surrogate marker of severe cytopenias. Transfusion affects patients’ quality of life, presents specific toxicities, and is known to affect immunity through the so-called transfusion-related immunomodulation that may affect CAR T-cell efficacy. We analyzed data from 671 patients from the French DESCAR-T registry for whom exhaustive transfusion data were available. Overall, 401 (59.8%) and 378 (56.3%) patients received transfusion in the 6-month period before and after CAR T-cell infusion, respectively. The number of patients receiving transfusion and the mean number of transfused products increased during the 6-month period before CAR T-cell infusion, peaked during the first month after infusion (early phase), and decreased over time. Predictive factors for transfusion at the early phase were age &gt;60 years, ECOG PS ≥2, treatment with axicabtagene ciloleucel, pre–CAR T-cell transfusions, and CAR-HEMATOTOX score ≥2. Predictive factors for late transfusion (between 1 and 6 months after infusion) were pre–CAR T-cell transfusions, CAR-HEMATOTOX score ≥2, ICANS ≥3 (for red blood cells [RBC] transfusion), and tocilizumab use (for platelets transfusion). Early transfusions and late platelets (but not RBC) transfusions were associated with a shorter progression-free survival and overall survival. Lymphoma-related mortality and nonrelapse mortality were both increased in the transfused population. Our data shed light on the mechanisms of early and late cytopenia and on the potential impact of transfusions on CAR T-cell efficacy and toxicity.</description><identifier>ISSN: 2473-9529</identifier><identifier>ISSN: 2473-9537</identifier><identifier>EISSN: 2473-9537</identifier><identifier>DOI: 10.1182/bloodadvances.2023011727</identifier><identifier>PMID: 38181767</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Antigens, CD19 ; Biomarkers ; Humans ; Immunobiology and Immunotherapy ; Immunotherapy, Adoptive - adverse effects ; Lymphoma, Large B-Cell, Diffuse - pathology ; Middle Aged ; Neoplasm Recurrence, Local ; Quality of Life</subject><ispartof>Blood advances, 2024-03, Vol.8 (6), p.1573-1585</ispartof><rights>2024 The American Society of Hematology</rights><rights>2024 by The American Society of Hematology. 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All other rights reserved. 2024 The American Society of Hematology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c430t-f4bf7f81ec9cdc36b69dff8a9f33d83e2fe4d94f2c669d20bedba67d0c4a74373</citedby><cites>FETCH-LOGICAL-c430t-f4bf7f81ec9cdc36b69dff8a9f33d83e2fe4d94f2c669d20bedba67d0c4a74373</cites><orcidid>0000-0003-1729-8213 ; 0000-0001-8755-5591 ; 0000-0002-3714-9824 ; 0000-0002-1038-0452 ; 0000-0003-0659-9635 ; 0000-0002-4460-5939 ; 0000-0002-8721-8357 ; 0000-0002-7791-0470 ; 0000-0003-2694-7510 ; 0000-0002-1156-8983 ; 0000-0002-0796-7914</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10982963/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10982963/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38181767$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vic, Samuel</creatorcontrib><creatorcontrib>Thibert, Jean-Baptiste</creatorcontrib><creatorcontrib>Bachy, Emmanuel</creatorcontrib><creatorcontrib>Cartron, Guillaume</creatorcontrib><creatorcontrib>Gastinne, Thomas</creatorcontrib><creatorcontrib>Morschhauser, Franck</creatorcontrib><creatorcontrib>Le Bras, Fabien</creatorcontrib><creatorcontrib>Bouabdallah, Kamal</creatorcontrib><creatorcontrib>Despas, Fabien</creatorcontrib><creatorcontrib>Bay, Jacques-Olivier</creatorcontrib><creatorcontrib>Rubio, Marie-Thérèse</creatorcontrib><creatorcontrib>Mohty, Mohamad</creatorcontrib><creatorcontrib>Casasnovas, Olivier</creatorcontrib><creatorcontrib>Choquet, Sylvain</creatorcontrib><creatorcontrib>Castilla-Llorente, Cristina</creatorcontrib><creatorcontrib>Guidez, Stéphanie</creatorcontrib><creatorcontrib>Loschi, Michaël</creatorcontrib><creatorcontrib>Guffroy, Blandine</creatorcontrib><creatorcontrib>Carras, Sylvain</creatorcontrib><creatorcontrib>Drieu La Rochelle, Laurianne</creatorcontrib><creatorcontrib>Guillet, Mathilde</creatorcontrib><creatorcontrib>Houot, Roch</creatorcontrib><title>Transfusion needs after CAR T-cell therapy for large B-cell lymphoma: predictive factors and outcome (a DESCAR-T study)</title><title>Blood advances</title><addtitle>Blood Adv</addtitle><description>•More than half of the patients need transfusion support after CAR T-cell therapy; various factors may affect transfusion needs.•Transfused patients have a poorer outcome with both an increased lymphoma-related mortality and nonrelapse mortality. [Display omitted] Chimeric antigen receptor (CAR) T-cells targeting CD19 have been approved for the treatment of relapse/refractory large B-cell lymphoma. Hematotoxicity is the most frequent CAR T-cell–related adverse event. Transfusion support is a surrogate marker of severe cytopenias. Transfusion affects patients’ quality of life, presents specific toxicities, and is known to affect immunity through the so-called transfusion-related immunomodulation that may affect CAR T-cell efficacy. We analyzed data from 671 patients from the French DESCAR-T registry for whom exhaustive transfusion data were available. Overall, 401 (59.8%) and 378 (56.3%) patients received transfusion in the 6-month period before and after CAR T-cell infusion, respectively. The number of patients receiving transfusion and the mean number of transfused products increased during the 6-month period before CAR T-cell infusion, peaked during the first month after infusion (early phase), and decreased over time. Predictive factors for transfusion at the early phase were age &gt;60 years, ECOG PS ≥2, treatment with axicabtagene ciloleucel, pre–CAR T-cell transfusions, and CAR-HEMATOTOX score ≥2. Predictive factors for late transfusion (between 1 and 6 months after infusion) were pre–CAR T-cell transfusions, CAR-HEMATOTOX score ≥2, ICANS ≥3 (for red blood cells [RBC] transfusion), and tocilizumab use (for platelets transfusion). Early transfusions and late platelets (but not RBC) transfusions were associated with a shorter progression-free survival and overall survival. Lymphoma-related mortality and nonrelapse mortality were both increased in the transfused population. Our data shed light on the mechanisms of early and late cytopenia and on the potential impact of transfusions on CAR T-cell efficacy and toxicity.</description><subject>Antigens, CD19</subject><subject>Biomarkers</subject><subject>Humans</subject><subject>Immunobiology and Immunotherapy</subject><subject>Immunotherapy, Adoptive - adverse effects</subject><subject>Lymphoma, Large B-Cell, Diffuse - pathology</subject><subject>Middle Aged</subject><subject>Neoplasm Recurrence, Local</subject><subject>Quality of Life</subject><issn>2473-9529</issn><issn>2473-9537</issn><issn>2473-9537</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkV9vFCEUxYnR2Kb2Kxge68NU_kwH8MW0a60mTUx0fSYMXLqYmWEEZpv99tJsu9onn7jknPu7cA9CmJJzSiV73w8xOuO2ZrKQzxlhnFAqmHiBjlkreKMuuHh5qJk6Qqc5_yKEUNHxC8VeoyMuqaw3cYzu18lM2S85xAlPAC5j4wskvLr8jteNhWHAZQPJzDvsY8KDSXeAr_bCsBvnTRzNBzwncMGWsAXsjS0xVczkcFyKjSPgM4M_Xf-oyGaNc1nc7t0b9MqbIcPp43mCfn6-Xq--NLffbr6uLm8b23JSGt_2XnhJwSrrLO_6TjnvpVGecyc5MA-tU61ntqsKIz243nTCEdsa0XLBT9DHPXde-hGchakkM-g5hdGknY4m6OfKFDb6Lm41JUoy1fFKOHskpPh7gVz0GPLD980EccmaKSaV6iSj1Sr3Vptizgn8YQ4l-iE7_Sw7_Te72vr233ceGp-SqoarvQHqtrYBks42QMW4kMAW7WL4_5Q_S2WyeQ</recordid><startdate>20240326</startdate><enddate>20240326</enddate><creator>Vic, Samuel</creator><creator>Thibert, Jean-Baptiste</creator><creator>Bachy, Emmanuel</creator><creator>Cartron, Guillaume</creator><creator>Gastinne, Thomas</creator><creator>Morschhauser, Franck</creator><creator>Le Bras, Fabien</creator><creator>Bouabdallah, Kamal</creator><creator>Despas, Fabien</creator><creator>Bay, Jacques-Olivier</creator><creator>Rubio, Marie-Thérèse</creator><creator>Mohty, Mohamad</creator><creator>Casasnovas, Olivier</creator><creator>Choquet, Sylvain</creator><creator>Castilla-Llorente, Cristina</creator><creator>Guidez, Stéphanie</creator><creator>Loschi, Michaël</creator><creator>Guffroy, Blandine</creator><creator>Carras, Sylvain</creator><creator>Drieu La Rochelle, Laurianne</creator><creator>Guillet, Mathilde</creator><creator>Houot, Roch</creator><general>Elsevier Inc</general><general>The American Society of Hematology</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-1729-8213</orcidid><orcidid>https://orcid.org/0000-0001-8755-5591</orcidid><orcidid>https://orcid.org/0000-0002-3714-9824</orcidid><orcidid>https://orcid.org/0000-0002-1038-0452</orcidid><orcidid>https://orcid.org/0000-0003-0659-9635</orcidid><orcidid>https://orcid.org/0000-0002-4460-5939</orcidid><orcidid>https://orcid.org/0000-0002-8721-8357</orcidid><orcidid>https://orcid.org/0000-0002-7791-0470</orcidid><orcidid>https://orcid.org/0000-0003-2694-7510</orcidid><orcidid>https://orcid.org/0000-0002-1156-8983</orcidid><orcidid>https://orcid.org/0000-0002-0796-7914</orcidid></search><sort><creationdate>20240326</creationdate><title>Transfusion needs after CAR T-cell therapy for large B-cell lymphoma: predictive factors and outcome (a DESCAR-T study)</title><author>Vic, Samuel ; 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various factors may affect transfusion needs.•Transfused patients have a poorer outcome with both an increased lymphoma-related mortality and nonrelapse mortality. [Display omitted] Chimeric antigen receptor (CAR) T-cells targeting CD19 have been approved for the treatment of relapse/refractory large B-cell lymphoma. Hematotoxicity is the most frequent CAR T-cell–related adverse event. Transfusion support is a surrogate marker of severe cytopenias. Transfusion affects patients’ quality of life, presents specific toxicities, and is known to affect immunity through the so-called transfusion-related immunomodulation that may affect CAR T-cell efficacy. We analyzed data from 671 patients from the French DESCAR-T registry for whom exhaustive transfusion data were available. Overall, 401 (59.8%) and 378 (56.3%) patients received transfusion in the 6-month period before and after CAR T-cell infusion, respectively. The number of patients receiving transfusion and the mean number of transfused products increased during the 6-month period before CAR T-cell infusion, peaked during the first month after infusion (early phase), and decreased over time. Predictive factors for transfusion at the early phase were age &gt;60 years, ECOG PS ≥2, treatment with axicabtagene ciloleucel, pre–CAR T-cell transfusions, and CAR-HEMATOTOX score ≥2. Predictive factors for late transfusion (between 1 and 6 months after infusion) were pre–CAR T-cell transfusions, CAR-HEMATOTOX score ≥2, ICANS ≥3 (for red blood cells [RBC] transfusion), and tocilizumab use (for platelets transfusion). Early transfusions and late platelets (but not RBC) transfusions were associated with a shorter progression-free survival and overall survival. Lymphoma-related mortality and nonrelapse mortality were both increased in the transfused population. 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2473-9537
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source MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection
subjects Antigens, CD19
Biomarkers
Humans
Immunobiology and Immunotherapy
Immunotherapy, Adoptive - adverse effects
Lymphoma, Large B-Cell, Diffuse - pathology
Middle Aged
Neoplasm Recurrence, Local
Quality of Life
title Transfusion needs after CAR T-cell therapy for large B-cell lymphoma: predictive factors and outcome (a DESCAR-T study)
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