-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

3517 Positron Emission Tomography Evaluation in Relapsed/Refractory B-Cell Lymphoma Patients Treated with Anti-19 Chimeric Antigen Receptor (CAR) T-Cells in the CART-SIE Observational Study

Program: Oral and Poster Abstracts
Session: 705. Cellular Immunotherapies: Late Phase and Commercially Available Therapies: Poster II
Hematology Disease Topics & Pathways:
Biological therapies, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Therapies
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Anna Dodero, MD1*, Anna Guidetti1*, Annalisa Chiappella, MD2, Silva Ljevar3*, Pier Luigi Zinzani, MD, PhD4, Beatrice Casadei, MD, PhD4*, Stefania Bramanti5*, Armando Santoro, MD6*, Patrizia Chiusolo, MD7*, Alice Di Rocco8*, Martina Di Palma, MD9*, Maria Chiara Tisi10*, Ilaria Cutini, MD11*, Matteo Giovanni Carrabba12*, Maurizio Musso13*, Massimo Martino, MD14*, Anna Maria Barbui, MD15*, Mattia Novo, MD16*, Giovanni Grillo17*, Marta Lisa Battista, MD18*, Manuela Zanni, MD19*, Luca Arcaini20*, Rosalba Miceli21*, Cristiana Carniti1* and Paolo Corradini, MD1

1Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
2Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Milano, Italy
3Department of Epidemiology and Data Science, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy, Milan, ITA
4Hematology, Istituto di Ematologia “Seràgnoli”, Bologna, Italy
5Humanitas Clinical and Research Center, IRCCS, Rozzano, Italy
6Humanitas Cancer Center, Rozzano, Mi, Italy
7Department of Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Policlinico Gemelli, ROMA, ITA
8Department of Cellular Biotechnology and Haematology, Sapienza University, Rome, Italy
9Department of Traslational and Precision Medicine, Sapienza University of Rome, Rome, Italy
10Hematology Unit, San Bortolo Hospital, A.U.L.S.S. 8 "Berica", Vicenza, Italy
11SOD Terapie Cellulari e Medicina Trasfusionale, AAD Trapianto di midollo osseo, Ospedale Careggi, Firenze, Italy
12Unit of Hematology and Bone Marrow Transplantation, I.R.C.C.S. Ospedale San Raffaele, Milan, Italy
13Division of Onco-Hematology and Stem Cell Transplantation, Clinica La Maddalena, Palermo, Italy
14Centro Unico Trapianti A, Grande Ospedale Metropolitano Bianchi Melacrino Morelli, Reggio Calabria, Italy
15Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy
16Hematology Division, A.O.U Città della Salute e della Scienza di Torino, Torino, Italy
17Stem Cell Transplantation, Azienda Ospedaliera Ospedale Niguarda Ca' Granda, Milano, Italy
18Clinic of Hematology and Cellular Therapies Unit, Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy
19Dipartimento di Medicina Traslazionale Università del Piemonte Orientale e SCDU Ematologia, Az Ospedaliera Santi Antonio e Biagio e Cesare Arrigo, Alessandria, Italy
20Department of Molecular Medicine, University of Pavia and Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
21Department of Epidemiology and Data Science, Unit of Biostatistics for Clinical Research, Milano, Italy

Background: CD19 direct chimeric antigen receptor (CAR) T-cell therapy is an efficacious therapy for patients (pts) affected by relapsed/refractory (R/R) large B-cell lymphomas (LBCL). The role of early evaluation by Positron emission tomography/computed tomography (PET/CT) is still undefined. The study's objective was to analyze the role of early PET/CT according to histology and CAR T-cell product administered.
Methods: CART-SIE is an ongoing prospective and retrospective observational study evaluating the outcome of lymphoma pts treated with CAR T-cells. From March 2019 to June 2023, 659 patients were enrolled. In this study, we included only pts with adequate follow-up (30 days) and an FDG-PET/CT before infusion (PET-0) and at least one month (PET-1) after CAR-T cells infusion. A landmark analysis based on PET-1 and PET-3 (3 months evaluation) results was performed for Progression-free survival (PFS) and Overall Survival (OS) estimation.
Results: Three hundred twenty-seven pts with R/R LBCL [n= 189 (58%) Diffuse large B-cell lymphomas, n= 59 (18%) High-grade B-cell lymphomas (HGBCL), n= 41 (13%) Primary Mediastinal B-cell lymphomas (PMBCL), n= 38 (11%) Mantle Cell Lymphoma (MCL)] received CAR T-cell treatment with axicabtagene-ciloleucel [n=161(49%), axicel], tisagenlecleucel [n=128 (39%), tisacel] or brexucabtagene autoleucel [n=38(12%), brexucel]. The median age of the pts was 58 years (90 pts were older than 65 years). Most pts [n=280, (85,6%)] were treated with a bridging therapy. Bulky and extranodal disease were observed in 108 (33%) and 177 (54,1%) pts, respectively. Pts who received tisacel were significantly older (p<0.0001), had a longer time from lymphocyte apheresis to the infusion (<0.0001), and did not include PMBCL. The median follow-up time was 12 months [IQR, 6,09-22,37]. At the time of PET-1, 180 pts (55%) showed a PET with DS1-3, 82(25%) had a PET with DS4 (n=61 PR, n=21 SD), and 65(20%) with DS5 (n=13 SD, n=47 PD, n=5 PR). The results of early PET were significantly different according to the histology (p<0.0005): the percentage of DS 4 and DS 5 was 22% and 23% for DLBCL, 30% and 31% for HGBCL, 39% and 7% for PMBCL, and 16% and 0% for MCL, respectively. Overall, 1-year PFS based on PET-1 was 67%, 42%, and 8% for DS1-3, DS4, and DS5 (p<0,0001), respectively. The prognostic role of DS 4 varied with histology: 1-year PFS was 36%, 58%, and 44% for DLBCL, PMBCL, and HGBCL (<0.0001), respectively. The outcome of early PET was significantly influenced by CAR T-cell product (also excluding PMBCL): 1-year PFS for pts with DS1-3 and DS4 at PET-1 was 66% and 51% for axicel and 58,7% and 32% for those treated with tisacel (p<0.0001). The 1-year OS based on PET-1 was 88%, 82%, and 33% for DS1-3, DS4, and DS5 (p<0,0001), respectively. At 90 days, only 219 pts were evaluable; 21 of 82 (26%) DS4 and 5 of 65 (8%) DS5 at PET-1 converted in CR. Overall, 1-year PFS and OS based on PET-3 was 80% and 93% for DS1-3, 64% and 93% for DS4, and 8% and 56% for DS5, respectively. Multivariable analyses identified DS4 and DS5 values on PET-1 and CAR T-cell product Tisacel associated with increasing risk of failure [HR: 1,95 (95%CI;1,01-3,76) for DS4; HR: 9,63 for DS5 (95%CI:6,13-15,13); p< 0,0001; HR: 1,53 for Tisacel vs Axicel; (95%CI:1,06-2,22); p<0.0231]. Conclusion: Early evaluation by PET significantly influenced the prognosis. Estimating the risk of failure must be integrated with CAR T- cell product.

Disclosures: Chiappella: Takeda: Other: lecture fee/educational activities, advisory board; AstraZeneca: Other: lecture fee/educational activities; Incyte: Other: lecture fee/educational activities; Jannsen-Cilag: Other: lecture fee/educational activities, advisory board; Novartis: Other: lecture fee/educational activities; Celgene-BMS: Other: lecture fee/educational activities, advisory board; SecuraBIO: Other: advisory board; Ideogen: Other: advisory board; Roche: Other: lecture fee/educational activities, advisory board; Gilead-Sciences: Other: lecture fee/educational activities, advisory board. Zinzani: MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADC THERAPEUTICS: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BEIGENE: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SECURA BIO: Membership on an entity's Board of Directors or advisory committees; CELLTRION: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; INCYTE: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SANDOZ: Membership on an entity's Board of Directors or advisory committees; SERVIER: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; JANSSEN-CILAG: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GILEAD: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ASTRAZENECA: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TAKEDA: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; EUSAPHARMA: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ROCHE: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; KYOWA KIRIN: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; NOVARTIS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Casadei: Lilly: Speakers Bureau; Beigene: Membership on an entity's Board of Directors or advisory committees; Celgene-BMS: Membership on an entity's Board of Directors or advisory committees; Roche: Speakers Bureau; Novartis: Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kite-Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Santoro: Sandoz: Speakers Bureau; Eli Lilly: Speakers Bureau; AstraZeneca: Speakers Bureau; Novartis: Speakers Bureau; Roche: Speakers Bureau; Takeda: Speakers Bureau; Amgen: Speakers Bureau; Abbvie: Speakers Bureau; Celgene (BMS): Speakers Bureau; Arqule: Other; Merck MSD: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Eisai: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy; Sanofi: Consultancy. Di Rocco: Janssen: Honoraria; Takeda: Speakers Bureau; Abbvie: Honoraria; Incyte: Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Novartis: Speakers Bureau; Roche: Honoraria, Speakers Bureau. Carniti: Novartis: Other: travel expenses. Corradini: Novartis: Other: Honoraria (Consulting, advisory role, or lecturer), Travel and accomodations; Janssen: Other: Honoraria (Consulting, advisory role, or lecturer), Travel and accomodations; Nerviano Medical Science: Other: Honoraria (Consulting, advisory role, or lecturer); Kyowa Kirin: Other: Honoraria (Consulting, advisory role, or lecturer); Incyte: Other: Honoraria (Consulting, advisory role, or lecturer); Gilead/Kite: Other: Honoraria (Consulting, advisory role, or lecturer), Travel and accomodations; Daiichi Sankyo: Other: Honoraria (Consulting, advisory role, or lecturer); Celgene: Other: Honoraria (Consulting, advisory role, or lecturer), Travel and accomodations; Amgen: Other: Honoraria (Consulting, advisory role, or lecturer), Travel and accomodations; ADC Theraputics (DSMB): Other: Honoraria (Consulting, advisory role, or lecturer); AbbVie: Other: Honoraria (Consulting, advisory role, or lecturer), Travel and accomodations; Roche: Other: Honoraria (Consulting, advisory role, or lecturer), Travel and accomodations; Pfizer: Other: Honoraria (Consulting, advisory role, or lecturer); Sanofi: Other: Honoraria (Consulting, advisory role, or lecturer); SOBI: Other: Honoraria (Consulting, advisory role, or lecturer); Takeda: Other: Honoraria (Consulting, advisory role, or lecturer), Travel and accomodations; GlaxoSmithKline: Other: Honoraria (Consulting, advisory role, or lecturer); BeiGene: Honoraria; Bristol Myers Squibb: Other: Travel and accomodations.

*signifies non-member of ASH