CAR T‐cell therapy induces a high rate of prolonged remission in relapsed primary CNS lymphoma: Real‐life results of the LOC network

The prognosis of relapsed primary central nervous system lymphoma (PCNSL) remains dismal. CAR T‐cells are a major contributor to systemic lymphomas, but their use in PCNSL is limited. From the LOC network database, we retrospectively selected PCNSL who had leukapheresis for CAR‐T cells from the thir...

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Veröffentlicht in:American journal of hematology 2024-07, Vol.99 (7), p.1240-1249
Hauptverfasser: Choquet, Sylvain, Soussain, Carole, Azar, Nabih, Morel, Véronique, Metz, Carole, Ursu, Renata, Waultier‐Rascalou, Agathe, Blasi, Roberta, Houot, Roch, Souchet, Laetitia, Roos‐Weil, Damien, Uzunov, Madalina, Quoc, Stéphanie Nguyen, Jacque, Nathalie, Boussen, Inès, Gauthier, Nicolas, Ouzegdouh, Maya, Blonski, Marie, Campidelli, Arnaud, Ahle, Guido, Guffroy, Blandine, Willems, Lise, Corvilain, Emilie, Barrie, Maryline, Alcantara, Marion, Garff‐Tavernier, Magali, Psimaras, Dimitri, Weiss, Nicolas, Baron, Marine, Bravetti, Clotilde, Hoang‐Xuan, Khê, Davi, Frédéric, Shor, Natalia, Alentorn, Agusti, Houillier, Caroline
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container_issue 7
container_start_page 1240
container_title American journal of hematology
container_volume 99
creator Choquet, Sylvain
Soussain, Carole
Azar, Nabih
Morel, Véronique
Metz, Carole
Ursu, Renata
Waultier‐Rascalou, Agathe
Blasi, Roberta
Houot, Roch
Souchet, Laetitia
Roos‐Weil, Damien
Uzunov, Madalina
Quoc, Stéphanie Nguyen
Jacque, Nathalie
Boussen, Inès
Gauthier, Nicolas
Ouzegdouh, Maya
Blonski, Marie
Campidelli, Arnaud
Ahle, Guido
Guffroy, Blandine
Willems, Lise
Corvilain, Emilie
Barrie, Maryline
Alcantara, Marion
Garff‐Tavernier, Magali
Psimaras, Dimitri
Weiss, Nicolas
Baron, Marine
Bravetti, Clotilde
Hoang‐Xuan, Khê
Davi, Frédéric
Shor, Natalia
Alentorn, Agusti
Houillier, Caroline
description The prognosis of relapsed primary central nervous system lymphoma (PCNSL) remains dismal. CAR T‐cells are a major contributor to systemic lymphomas, but their use in PCNSL is limited. From the LOC network database, we retrospectively selected PCNSL who had leukapheresis for CAR‐T cells from the third line of treatment, and, as controls, PCNSL treated with any treatment, at least in the third line and considered not eligible for ASCT. Twenty‐seven patients (median age: 68, median of three previous lines, including ASCT in 14/27) had leukapheresis, of whom 25 received CAR T‐cells (tisa‐cel: N = 16, axi‐cel: N = 9) between 2020 and 2023. All but one received a bridging therapy. The median follow‐up after leukapheresis was 20.8 months. The best response after CAR‐T cells was complete response in 16 patients (64%). One‐year progression‐free survival from leukapheresis was 43% with a plateau afterward. One‐year relapse‐free survival was 79% for patients in complete or partial response at CAR T‐cell infusion. The median overall survival was 21.2 months. Twenty‐three patients experienced a cytokine release syndrome and 17/25 patients (68%) a neurotoxicity (five grade ≥3). The efficacy endpoints were significantly better in the CAR T‐cell group than in the control group (N = 247) (median PFS: 3 months; median OS: 4.7 months; p 
doi_str_mv 10.1002/ajh.27316
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CAR T‐cells are a major contributor to systemic lymphomas, but their use in PCNSL is limited. From the LOC network database, we retrospectively selected PCNSL who had leukapheresis for CAR‐T cells from the third line of treatment, and, as controls, PCNSL treated with any treatment, at least in the third line and considered not eligible for ASCT. Twenty‐seven patients (median age: 68, median of three previous lines, including ASCT in 14/27) had leukapheresis, of whom 25 received CAR T‐cells (tisa‐cel: N = 16, axi‐cel: N = 9) between 2020 and 2023. All but one received a bridging therapy. The median follow‐up after leukapheresis was 20.8 months. The best response after CAR‐T cells was complete response in 16 patients (64%). One‐year progression‐free survival from leukapheresis was 43% with a plateau afterward. One‐year relapse‐free survival was 79% for patients in complete or partial response at CAR T‐cell infusion. The median overall survival was 21.2 months. Twenty‐three patients experienced a cytokine release syndrome and 17/25 patients (68%) a neurotoxicity (five grade ≥3). The efficacy endpoints were significantly better in the CAR T‐cell group than in the control group (N = 247) (median PFS: 3 months; median OS: 4.7 months; p &lt; 0.001). This series represents the largest cohort of PCNSL treated with CAR T‐cells reported worldwide. CAR T‐cells are effective in relapsed PCNSL, with a high rate of long‐term remission and a reassuring tolerance profile. 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CAR T‐cells are a major contributor to systemic lymphomas, but their use in PCNSL is limited. From the LOC network database, we retrospectively selected PCNSL who had leukapheresis for CAR‐T cells from the third line of treatment, and, as controls, PCNSL treated with any treatment, at least in the third line and considered not eligible for ASCT. Twenty‐seven patients (median age: 68, median of three previous lines, including ASCT in 14/27) had leukapheresis, of whom 25 received CAR T‐cells (tisa‐cel: N = 16, axi‐cel: N = 9) between 2020 and 2023. All but one received a bridging therapy. The median follow‐up after leukapheresis was 20.8 months. The best response after CAR‐T cells was complete response in 16 patients (64%). One‐year progression‐free survival from leukapheresis was 43% with a plateau afterward. One‐year relapse‐free survival was 79% for patients in complete or partial response at CAR T‐cell infusion. The median overall survival was 21.2 months. Twenty‐three patients experienced a cytokine release syndrome and 17/25 patients (68%) a neurotoxicity (five grade ≥3). The efficacy endpoints were significantly better in the CAR T‐cell group than in the control group (N = 247) (median PFS: 3 months; median OS: 4.7 months; p &lt; 0.001). This series represents the largest cohort of PCNSL treated with CAR T‐cells reported worldwide. CAR T‐cells are effective in relapsed PCNSL, with a high rate of long‐term remission and a reassuring tolerance profile. 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Soussain, Carole ; Azar, Nabih ; Morel, Véronique ; Metz, Carole ; Ursu, Renata ; Waultier‐Rascalou, Agathe ; Blasi, Roberta ; Houot, Roch ; Souchet, Laetitia ; Roos‐Weil, Damien ; Uzunov, Madalina ; Quoc, Stéphanie Nguyen ; Jacque, Nathalie ; Boussen, Inès ; Gauthier, Nicolas ; Ouzegdouh, Maya ; Blonski, Marie ; Campidelli, Arnaud ; Ahle, Guido ; Guffroy, Blandine ; Willems, Lise ; Corvilain, Emilie ; Barrie, Maryline ; Alcantara, Marion ; Garff‐Tavernier, Magali ; Psimaras, Dimitri ; Weiss, Nicolas ; Baron, Marine ; Bravetti, Clotilde ; Hoang‐Xuan, Khê ; Davi, Frédéric ; Shor, Natalia ; Alentorn, Agusti ; Houillier, Caroline</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4226-b92758f9bb7145b4a08cd9050959fba74ecc8e449f74a8622fda7420f7ccec8b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Cancer</topic><topic>Cell therapy</topic><topic>Central nervous system</topic><topic>Central Nervous System Neoplasms - mortality</topic><topic>Central Nervous System Neoplasms - therapy</topic><topic>Female</topic><topic>Humans</topic><topic>Immunological tolerance</topic><topic>Immunotherapy, Adoptive - adverse effects</topic><topic>Immunotherapy, Adoptive - methods</topic><topic>Leukapheresis</topic><topic>Life Sciences</topic><topic>Lymphocytes T</topic><topic>Lymphoma</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Middle Aged</topic><topic>Neurotoxicity</topic><topic>Receptors, Chimeric Antigen</topic><topic>Remission</topic><topic>Remission Induction</topic><topic>Retrospective Studies</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Choquet, Sylvain</creatorcontrib><creatorcontrib>Soussain, Carole</creatorcontrib><creatorcontrib>Azar, Nabih</creatorcontrib><creatorcontrib>Morel, Véronique</creatorcontrib><creatorcontrib>Metz, Carole</creatorcontrib><creatorcontrib>Ursu, Renata</creatorcontrib><creatorcontrib>Waultier‐Rascalou, Agathe</creatorcontrib><creatorcontrib>Blasi, Roberta</creatorcontrib><creatorcontrib>Houot, Roch</creatorcontrib><creatorcontrib>Souchet, Laetitia</creatorcontrib><creatorcontrib>Roos‐Weil, Damien</creatorcontrib><creatorcontrib>Uzunov, Madalina</creatorcontrib><creatorcontrib>Quoc, Stéphanie Nguyen</creatorcontrib><creatorcontrib>Jacque, Nathalie</creatorcontrib><creatorcontrib>Boussen, Inès</creatorcontrib><creatorcontrib>Gauthier, Nicolas</creatorcontrib><creatorcontrib>Ouzegdouh, Maya</creatorcontrib><creatorcontrib>Blonski, Marie</creatorcontrib><creatorcontrib>Campidelli, Arnaud</creatorcontrib><creatorcontrib>Ahle, Guido</creatorcontrib><creatorcontrib>Guffroy, Blandine</creatorcontrib><creatorcontrib>Willems, Lise</creatorcontrib><creatorcontrib>Corvilain, Emilie</creatorcontrib><creatorcontrib>Barrie, Maryline</creatorcontrib><creatorcontrib>Alcantara, Marion</creatorcontrib><creatorcontrib>Garff‐Tavernier, Magali</creatorcontrib><creatorcontrib>Psimaras, Dimitri</creatorcontrib><creatorcontrib>Weiss, Nicolas</creatorcontrib><creatorcontrib>Baron, Marine</creatorcontrib><creatorcontrib>Bravetti, Clotilde</creatorcontrib><creatorcontrib>Hoang‐Xuan, Khê</creatorcontrib><creatorcontrib>Davi, Frédéric</creatorcontrib><creatorcontrib>Shor, Natalia</creatorcontrib><creatorcontrib>Alentorn, Agusti</creatorcontrib><creatorcontrib>Houillier, Caroline</creatorcontrib><collection>Wiley Online Library (Open Access Collection)</collection><collection>Wiley Online Library (Open Access Collection)</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>American journal of hematology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Choquet, Sylvain</au><au>Soussain, Carole</au><au>Azar, Nabih</au><au>Morel, Véronique</au><au>Metz, Carole</au><au>Ursu, Renata</au><au>Waultier‐Rascalou, Agathe</au><au>Blasi, Roberta</au><au>Houot, Roch</au><au>Souchet, Laetitia</au><au>Roos‐Weil, Damien</au><au>Uzunov, Madalina</au><au>Quoc, Stéphanie Nguyen</au><au>Jacque, Nathalie</au><au>Boussen, Inès</au><au>Gauthier, Nicolas</au><au>Ouzegdouh, Maya</au><au>Blonski, Marie</au><au>Campidelli, Arnaud</au><au>Ahle, Guido</au><au>Guffroy, Blandine</au><au>Willems, Lise</au><au>Corvilain, Emilie</au><au>Barrie, Maryline</au><au>Alcantara, Marion</au><au>Garff‐Tavernier, Magali</au><au>Psimaras, Dimitri</au><au>Weiss, Nicolas</au><au>Baron, Marine</au><au>Bravetti, Clotilde</au><au>Hoang‐Xuan, Khê</au><au>Davi, Frédéric</au><au>Shor, Natalia</au><au>Alentorn, Agusti</au><au>Houillier, Caroline</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CAR T‐cell therapy induces a high rate of prolonged remission in relapsed primary CNS lymphoma: Real‐life results of the LOC network</atitle><jtitle>American journal of hematology</jtitle><addtitle>Am J Hematol</addtitle><date>2024-07</date><risdate>2024</risdate><volume>99</volume><issue>7</issue><spage>1240</spage><epage>1249</epage><pages>1240-1249</pages><issn>0361-8609</issn><issn>1096-8652</issn><eissn>1096-8652</eissn><abstract>The prognosis of relapsed primary central nervous system lymphoma (PCNSL) remains dismal. CAR T‐cells are a major contributor to systemic lymphomas, but their use in PCNSL is limited. From the LOC network database, we retrospectively selected PCNSL who had leukapheresis for CAR‐T cells from the third line of treatment, and, as controls, PCNSL treated with any treatment, at least in the third line and considered not eligible for ASCT. Twenty‐seven patients (median age: 68, median of three previous lines, including ASCT in 14/27) had leukapheresis, of whom 25 received CAR T‐cells (tisa‐cel: N = 16, axi‐cel: N = 9) between 2020 and 2023. All but one received a bridging therapy. The median follow‐up after leukapheresis was 20.8 months. The best response after CAR‐T cells was complete response in 16 patients (64%). One‐year progression‐free survival from leukapheresis was 43% with a plateau afterward. One‐year relapse‐free survival was 79% for patients in complete or partial response at CAR T‐cell infusion. The median overall survival was 21.2 months. Twenty‐three patients experienced a cytokine release syndrome and 17/25 patients (68%) a neurotoxicity (five grade ≥3). The efficacy endpoints were significantly better in the CAR T‐cell group than in the control group (N = 247) (median PFS: 3 months; median OS: 4.7 months; p &lt; 0.001). This series represents the largest cohort of PCNSL treated with CAR T‐cells reported worldwide. CAR T‐cells are effective in relapsed PCNSL, with a high rate of long‐term remission and a reassuring tolerance profile. The results seem clearly superior to those usually observed in this setting.</abstract><cop>Hoboken, USA</cop><pub>John Wiley &amp; Sons, Inc</pub><pmid>38586986</pmid><doi>10.1002/ajh.27316</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0003-2931-7522</orcidid><orcidid>https://orcid.org/0000-0002-7767-755X</orcidid><orcidid>https://orcid.org/0000-0002-0877-2289</orcidid><orcidid>https://orcid.org/0000-0003-0212-8684</orcidid><orcidid>https://orcid.org/0000-0002-1099-9597</orcidid><orcidid>https://orcid.org/0000-0002-5226-664X</orcidid><orcidid>https://orcid.org/0000-0002-3764-063X</orcidid><orcidid>https://orcid.org/0000-0002-6641-288X</orcidid><orcidid>https://orcid.org/0000-0002-2408-059X</orcidid><orcidid>https://orcid.org/0000-0002-3131-3240</orcidid><orcidid>https://orcid.org/0000-0003-0693-1829</orcidid><orcidid>https://orcid.org/0000-0003-0123-8937</orcidid><orcidid>https://orcid.org/0000-0002-2479-0348</orcidid><orcidid>https://orcid.org/0000-0003-1442-8748</orcidid><orcidid>https://orcid.org/0000-0002-7791-0470</orcidid><orcidid>https://orcid.org/0000-0003-1729-8213</orcidid><orcidid>https://orcid.org/0000-0002-5254-3483</orcidid><orcidid>https://orcid.org/0000-0002-2912-0343</orcidid><orcidid>https://orcid.org/0000-0001-9001-573X</orcidid><orcidid>https://orcid.org/0000-0001-5155-196X</orcidid><oa>free_for_read</oa></addata></record>
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identifier ISSN: 0361-8609
ispartof American journal of hematology, 2024-07, Vol.99 (7), p.1240-1249
issn 0361-8609
1096-8652
1096-8652
language eng
recordid cdi_hal_primary_oai_HAL_hal_04574661v1
source Wiley Online Library - AutoHoldings Journals; MEDLINE
subjects Adult
Aged
Aged, 80 and over
Cancer
Cell therapy
Central nervous system
Central Nervous System Neoplasms - mortality
Central Nervous System Neoplasms - therapy
Female
Humans
Immunological tolerance
Immunotherapy, Adoptive - adverse effects
Immunotherapy, Adoptive - methods
Leukapheresis
Life Sciences
Lymphocytes T
Lymphoma
Male
Medical prognosis
Middle Aged
Neurotoxicity
Receptors, Chimeric Antigen
Remission
Remission Induction
Retrospective Studies
title CAR T‐cell therapy induces a high rate of prolonged remission in relapsed primary CNS lymphoma: Real‐life results of the LOC network
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