{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:43:11Z","timestamp":1792183391812,"version":"4.4.0"},"reference-count":11,"publisher":"American Society of Hematology","issue":"11","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,6,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Tisagenlecleucel demonstrated high response rates and a manageable safety profile in adults with relapsed\/refractory diffuse large B-cell lymphoma (r\/r DLBCL) in the JULIET trial. However, lack of response and chimeric antigen receptor (CAR) T-cell exhaustion were observed in patients with programmed cell death protein 1 (PD-1) overexpression. Hence, pembrolizumab, a PD-1 inhibitor, was hypothesized to improve efficacy and cellular expansion of CAR T-cells in\u00a0vivo. Here, we report the final analysis of the PORTIA trial in adult patients with r\/r DLBCL who had \u22652 prior lines of therapy and had an Eastern Cooperative Oncology Group performance status of \u22641. Patients received 1 tisagenlecleucel infusion on day 1. Pembrolizumab (200 mg) was given every 21 days, for up to 6 doses. Three cohorts initiated pembrolizumab on days 15 (n\u00a0= 4), 8 (n\u00a0= 4), or \u20131 (n\u00a0= 4). Safety, efficacy, cellular kinetics, and biomarker analyses were included. Tisagenlecleucel plus\u00a0pembrolizumab was feasible and showed a manageable safety profile, without dose-limiting toxicities. Emerging efficacy with tisagenlecleucel was observed when pembrolizumab was given the day before tisagenlecleucel; however, the limited patient sample and short follow-up do not allow for definitive conclusions. Adding pembrolizumab to tisagenlecleucel did not augment the cellular expansion of tisagenlecleucel but delayed peak expansion if given the day before tisagenlecleucel (NCT03630159).<\/jats:p>","DOI":"10.1182\/bloodadvances.2022007779","type":"journal-article","created":{"date-parts":[[2022,8,31]],"date-time":"2022-08-31T13:03:38Z","timestamp":1661951018000},"page":"2283-2286","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":48,"title":["Safety and efficacy of tisagenlecleucel plus pembrolizumab in patients with r\/r DLBCL: phase 1b PORTIA study results"],"prefix":"10.1182","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9826-1062","authenticated-orcid":false,"given":"Ulrich","family":"Jaeger","sequence":"first","affiliation":[{"name":"1Division of Hematology and Hemostaseology and Comprehensive Cancer Center, Department of Medicine I, Medical University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3599-8099","authenticated-orcid":false,"given":"Nina","family":"Worel","sequence":"additional","affiliation":[{"name":"2Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0539-4796","authenticated-orcid":false,"given":"Joseph P.","family":"McGuirk","sequence":"additional","affiliation":[{"name":"3Hematologic Malignancies and Cellular Therapeutics, The University of Kansas Health System, Kansas City, KS"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2719-0580","authenticated-orcid":false,"given":"Peter A.","family":"Riedell","sequence":"additional","affiliation":[{"name":"4David and Etta Jonas Center for Cellular Therapy, University of Chicago, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Fleury","sequence":"additional","affiliation":[{"name":"5Maisonneuve-Rosement Hospital, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Du","sequence":"additional","affiliation":[{"name":"6Novartis Institutes for Biomedical Research, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Han","sequence":"additional","affiliation":[{"name":"7Novartis Pharmaceuticals Corporation, East Hanover, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Pearson","sequence":"additional","affiliation":[{"name":"8Novartis Institutes for BioMedical Research, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santiago","family":"Redondo","sequence":"additional","affiliation":[{"name":"9Novartis Farmaceutica S.A., Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0816-6729","authenticated-orcid":false,"given":"Edmund K.","family":"Waller","sequence":"additional","affiliation":[{"name":"10Bone Marrow and Stem Cell Transplant Center, Winship Cancer Institute of Emory University, Atlanta, GA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","published-online":{"date-parts":[[2023,5,24]]},"reference":[{"issue":"10","key":"2023061215525885700_bib1","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1016\/S1470-2045(21)00375-2","article-title":"Long-term clinical outcomes of tisagenlecleucel in patients with relapsed or refractory aggressive B-cell lymphomas (JULIET): a multicentre, open-label, single-arm, phase 2 study","volume":"22","author":"Schuster","year":"2021","journal-title":"Lancet Oncol"},{"issue":"12","key":"2023061215525885700_bib2","doi-asserted-by":"crossref","first-page":"4118","DOI":"10.3390\/ijms19124118","article-title":"Oligoclonal T cells transiently expand and express Tim-3 and PD-1 following anti-CD19 CAR T Cell therapy: a\u00a0case report","volume":"19","author":"Funk","year":"2018","journal-title":"Int J Mol Sci"},{"issue":"1","key":"2023061215525885700_bib3","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1056\/NEJMoa1804980","article-title":"Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma","volume":"380","author":"Schuster","year":"2019","journal-title":"N\u00a0Engl J Med"},{"issue":"8","key":"2023061215525885700_bib4","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1182\/blood-2016-09-738245","article-title":"PD-1 blockade modulates chimeric antigen receptor (CAR)-modified T cells: refueling the CAR","volume":"129","author":"Chong","year":"2017","journal-title":"Blood"},{"issue":"suppl 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analysis of ZUMA-6: Axicabtagene ciloleucel (Axi-Cel) in combination with atezolizumab (Atezo) for the treatment of patients (Pts) with refractory diffuse large B cell lymphoma (DLBCL)","volume":"80","author":"Jacobson","year":"2020","journal-title":"Cancer Res"},{"key":"2023061215525885700_bib9","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2019.00767","article-title":"Anti-CD19 chimeric antigen receptor T cells in combination with nivolumab are safe and effective against relapsed\/refractory B-cell non-Hodgkin lymphoma","volume":"9","author":"Cao","year":"2019","journal-title":"Front Oncol"},{"issue":"5","key":"2023061215525885700_bib10","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.ccell.2019.09.006","article-title":"Combination immunotherapy with CAR T cells and checkpoint blockade for the treatment of solid tumors","volume":"36","author":"Grosser","year":"2019","journal-title":"Cancer Cell"},{"issue":"suppl 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Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/bloodadvances\/article-pdf\/7\/11\/2283\/2056769\/blooda_adv-2022-007779-main.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/bloodadvances\/article-pdf\/7\/11\/2283\/2056769\/blooda_adv-2022-007779-main.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T11:53:39Z","timestamp":1686570819000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/bloodadvances\/article\/7\/11\/2283\/486461\/Safety-and-efficacy-of-tisagenlecleucel-plus"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,24]]},"references-count":11,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2023,6,13]]}},"URL":"https:\/\/doi.org\/10.1182\/bloodadvances.2022007779","relation":{},"ISSN":["2473-9529","2473-9537"],"issn-type":[{"value":"2473-9529","type":"print"},{"value":"2473-9537","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,24]]}}}