Stringent Nationwide Selection Criteria for CAR-T Cell Therapy Ensure Favourable Outcome of Patients with LBCL - First Data from the Austrian CAR-T Network

Background: The national Austrian CAR-T network (AT-CAR-T network) consists of 6 CAR-T cell centers and established a stringent nation-wide selection algorithm in order to ensure quality-controlled and regulated access for patients with relapsed/refractory large B-cell lymphomas (LBCL) in line with the EMA-label. Patients were selected according to this algorithm and therapy was approved by local tumor-boards. The algorithm allocates candidates to 3 categories: i) eligible, ii) to be discussed and iii) non-eligible for CAR-T treatment based on 5 major (cardiac and lung function, ECOG performance status, active CNS involvement and current infections) and 7 minor criteria. We here present our first nation-wide outcome analysis assessing the efficacy of the selection process using retrospective real-life data collected over the last three years including efficacy and toxicity data.

Patients and methods: Between September 2019 and February 2022, 45 patients were selected strictly based on the selection algorithm including an ECOG <2 and treated with one of the two approved compounds (tisagenlecleucel/ Kymriah® or axicabtagen ciloleucel/ Yescarta®). All patients have signed IC before being treated with these approved products. The analysis included patient characteristics, efficacy and adverse event data. Patients treated with "out of specification" products were also documented.

Results: At the time of this analysis, 45 r/r LBCL (n=44 DLBCL-NOS thereof n=13 HGL/ DHL (double hit lymphoma) or THL (triple hit lymphoma), n=1 PMBCL), n=6 pediatric ALL (pALL) patients. IPI was <3 in most patients and >3 in n=6 LBCL patients. Twenty-three patients received tisagenlecleucel and twenty-two patients axicabtagen ciloleucel. Additionally, 6 pALL patients received tisagenlecleucel, but were not selected by the Austrian Selection Algorithm. Therefore, analysis focuses on mainly the LBCL pts. The median number of previous treatment lines was 3 (range 2-7), including autologous transplant (n=15; 33.3%). Bridging therapy was administered in 39 pts (86.7%) consisting of radiotherapy (RT, n=6), combined immunochemotherapy with various regimens mainly Pola-RB (n=9), but also some with R-GeMOX (n=2), R-ICE (n=1), R-GDP (n=3), R-DHAP (n=1), dexamethasone monotherapy (n=3), bispecific antibodies like glofitamab (n=3), small molecules alone or in combination with obinotuzumab, or amongst others ibrutinib (n=2), idelalisib (n=1), lenalidomide (n=3), venetoclax (n=2). PET-CT-scan based response assessment at month 3 after CAR T-infusion was available for n=38 LBCL patients (ORR=62,2%: CR=53,3%, PR=8,9%; SD=2,2%; PD=20%). The median follow-up period for patients censored at last observation was 9.6 months (interquartile range: 5.2-20.2). The 6mo PFS and OS is 74% [95%CI:60-87%] and 87% [95%CI:76-98%] and 12mo PFS and OS is 70% [95%CI:55-84%] and 78% [95%CI:62-93%], respectively. The median PFS and OS calculated from the time of CAR-T administration (d0) was not reached in the overall cohort. Three of six pALL patients were in CR at month 3 after CAR-T infusion, four of the pALL pts relapsed, whereas 5 are still alive being rescued by an allogeneic transplant or a second CAR-T infusion. Side effects were well manageable in all cases. Grade 3 AE like CRS occurred in 2 LBCL patients (axicabtagen ciloleucel), ICANS ≥3 in 4 LBCL cases (1 tisagenlecleucel /3 axicabtagen ciloleucel). We did not observe therapy-related mortality. Long-term neutropenia after day 28 was observed in 9 patients.

Summary/Conclusion: Our results support the use of a nationwide consensus for CAR-T patient selection criteria, which serves as basis for local patient allocation. This first analysis of AT-CAR-T patients selected based on a defined algorithm demonstrates favorable outcome and is well comparable to other approaches using centralized selection criteria, e.g. with the French DESCAR-T data. Our data further support that co-morbidities and fitness of CAR-T candidates need to be acknowledged. The limitation of our data is the rather small patient cohort and lack of outcome data for individuals refused for CAR-T cell therapy based on the AT-CAR-T algorithm.

Rudzki:Roche: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Kite-Gilead: Consultancy, Honoraria, Other: travel support , Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene-BMS: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Other: travel support , Research Funding. Jaeger:Roche: Consultancy, Honoraria, Research Funding; Miltenyi Biomedicine: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Research Funding; Gilead: Honoraria; BMS Celgene: Honoraria; Janssen: Consultancy, Honoraria; Abbvie: Honoraria; Sanofi: Honoraria; MSD: Honoraria; Beigene: Honoraria; Incyte: Honoraria; Acerta: Honoraria. Wolf:Novartis: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; BMS/Celgene: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria, Research Funding; Roche: Honoraria, Research Funding; MSD: Honoraria, Research Funding; GEMOAB: Honoraria. Petzer:Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Sandoz: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite-Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Saegen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support. Greil:AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, expenses, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, expenses, Research Funding; Daiichi Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, expenses, Research Funding; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, expenses, Research Funding; MSD Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, expenses, Research Funding; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, expenses, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, expenses, Research Funding; Astra Zeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, expenses, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, expenses, Research Funding; BMS-Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, expenses, Research Funding; Hoffmann - La Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, expenses, Research Funding. Peters:Riemser: Consultancy, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Jazz: Other, Research Funding; Neovii: Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Medac: Honoraria. Greinix:Gilead, Novartis, Sanofi, Cellgene: Consultancy; Amgen, Gilead, Novartis, Sanofi, Takeda, Therakos: Speakers Bureau. Attarbaschi:Novartis: Honoraria; Gilead: Honoraria; MSD: Honoraria; Pfizer: Honoraria; Takeda: Honoraria; Amgen: Honoraria; Jazz: Honoraria. Buxhofer-Ausch:Kite-Gilead: Consultancy, Honoraria; Celgene-BMS: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Leisch:Gilead-kite: Consultancy, Honoraria; BMS-Celgene: Consultancy, Honoraria, Other: travel support; Novartis: Consultancy, Honoraria, Other: travel support; Takeda: Consultancy, Honoraria. Schlenke:Cerus Corp USA: Honoraria, Research Funding. Schmitt:Takeda: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Research Funding; BMS/Celgene: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria, Research Funding; abbvie: Consultancy, Honoraria. Worel:Therakos Mallinckrodt: Honoraria; Sanofi Genzyme: Honoraria, Other: research fund; Kite Gilead: Honoraria; Novartis: Honoraria; Janssens: Honoraria. Wohlfarth:BMS-Celgene: Consultancy, Honoraria; Gilead/kite: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau.

3 patients received glofitamab (bispecific antibody, BITEs) by a named patient use programm, being ineligible for CAR-T Treatment. But during treatment (after 2 cycles), all 3 patients responded to the BITEs to a certain extent so that they reversed to be CAR-T eligible and continued with CAR-T administration.