-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.

3131 Outcomes of CAR T-Cells Therapy in High-Grade B-Cell Lymphomas Compared to Diffuse Large B-Cell Lymphomas: A Weighted Comparison Analysis from CAR-T SIE Study

Program: Oral and Poster Abstracts
Session: 628. Aggressive Lymphomas: Cellular Therapies: Poster II
Hematology Disease Topics & Pathways:
Research, Lymphomas, Non-Hodgkin lymphoma, Clinical Research, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Diseases, Real-world evidence, Treatment Considerations, Biological therapies, Lymphoid Malignancies
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Anna Dodero, MD1*, Giusy Ceparano, MD1,2*, Beatrice Casadei, MD3*, Piera Angelillo, MD4*, Stefania Bramanti5*, Maria Chiara Tisi6*, Silva Ljevar7*, Annalisa Chiappella8, Barbara Botto9*, Ilaria Cutini10*, Patrizia Chiusolo, MD, PhD11,12*, Anna Maria Barbui, MD13*, Mirko Farina, MD14*, Alice Di Rocco, MD15*, Giovanni Grillo16*, Jacopo Olivieri, MD17*, Mauro Krampera18, Lucia Brunello, PhD19*, Anna Guidetti, MD20*, Pier Luigi Zinzani, MD, PhD3,21, Cristiana Carniti, PhD20* and Paolo Corradini, MD20,22

1Hematology and Stem Cell Transplantation, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
2Department of Hematology and Stem Cell Transplantation, Fondazione IRCCS Istituto Nazionale dei Tumori; Università degli Studi di Milano, Milano, Italy
3IRCCS Azienda Ospedaliero-Universitaria di Bologna  Istituto di Ematologia “Seràgnoli”, Bologna, Italy
4Lymphoma Unit, IRCCS San Raffaele Scientific Institute, Milano, Italy
5Bone Marrow Transplantation and Cell Therapy Unit, IRCCS Humanitas Research Hospital, Rozzano, Italy
6Hematology Unit, San Bortolo Hospital, A.U.L.S.S. 8 "Berica", Vicenza, Italy
7Unit of Biostatistics for Clinical Research Department of Data Science, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
8Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
9Division of Hematology, Città della Salute e della Scienza Hospital and University, Torino, Italy
10Department of Cellular Therapies and Transfusion Medicine, Careggi University Hospital, Firenze, Italy
11Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy
12Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Università Cattolica del Sacro Cuore, Rome, Italy
13Department of Oncology and Hematology, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy
14Unit of Blood Diseases and Bone Marrow Transplantation, Cell Therapies and Hematology Research Program, Department of Clinical and Experimental Science, University of Brescia, ASST Spedali Civili di Brescia, University of Brescia, ASST Spedali Civili, Brescia, Italy
15Hematology Section, Department of Traslational and Precision Medicine, Sapienza University of Rome, Roma, Italy
16Department of Hematology and Stem Cell Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy
17Clinica Ematologica, Centro Trapianti e Terapie Cellulari "Carlo Melzi", Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italy
18UOC di Ematologia e Centro Trapianto di Midollo Osseo, Azienda Ospedaliera Universitaria Integrata Verona Policlinico G.B. Rossi, Verona, Italy
19Hematology, AZienda Ospedaliera Santi Antonio e Biagio e CEsare Arrigo, Alessandria, Italy
20Division of Hematology and Stem Cell Transplantation, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
21University of Bologna, Bologna, Italy
22University of Milan, Milano, Italy

Background: High-grade B-cell lymphomas (HGBL) account for 10% of all aggressive lymphomas and include double-hit/triple-hit (DH/TH), characterized by myc/bcl2 or myc/bcl2/bcl6 rearrangements and HGBL not otherwise specified (NOS). This category previously included also diffuse large B-cell lymphomas (DLBCL) with myc/bcl6 rearrangements. Due to biological and clinical characteristics, the risk of relapse remains high following first-line intensive treatments. Approval of anti-CD19 Chimeric Antigen Receptor (CAR) T-cells for third-line aggressive lymphomas has resulted in long-term remission in up to 40% of pts. Recent studies have demonstrated similar efficacy of CAR T-cells therapy in the HGBL subgroup versus DLBCL. However, these studies included few HGBL pts with limited long-term follow-up results. The present study compares the outcomes of patients affected by HGBL and DLBCL treated with CAR T-cells using a weighted comparison analysis and evaluates the response to salvage therapy following treatment failure.

Methods: Pts diagnosed with relapsed/refractory HGBL and DLBCL who received commercial CAR T-cells in the third line or beyond between February 2020 and January 2024 were included. All data were collected from the CAR-T SIE prospective observational study. When available, histological reports and FISH analyses were centrally collected. Propensity score inverse probability weighting (IPW) was used to create a balanced covariate distribution between pts with HGBL and those with DLBCL. Covariates used for propensity score construction included age, sex, C-reactive protein (CRP), ECOG, refractory vs relapsed, International Prognostic Index, number of prior lines of treatment, previous ASCT, response to bridge, bulky disease, CAR T-cells product, and vein-to-vein time.

Results: We analyzed a population of 420 pts: 66 HGBL [n=41 HGBL DH/TH, n=20 HGBL NOS, n=5 DLBCL myc/bcl6] and 354 DLBCL [n=278 de-novo DLBCL (79%), n=76 transformed DLBCL (21%)]. All pts were treated with axicabtagene ciloleucel (axicel) (n=206, 49%) or tisagenlecleucel (tisacel) (n=214, 51%). The median follow-up was 23.5 months for HGBL and 18.1 months for DLBCL. Before weighting, DLBCL pts exhibited higher CRP at infusion, number of previous lines >2, and higher use of tisacel than HGBL pts. Overall, 62 of 66 (94%) and 279 of 354 (79%) received bridging therapy with no statistically significant difference in overall response rate (31% in HGBL vs 38% in DLBCL, p=0.250). In univariable analysis, the OS was significantly lower in HGBL than in DLBCL, (24-month OS 39% vs. 49%, log-rank p=0.025) but not PFS (24-months PFS 35% vs. 33%, log-rank p=0.529). Interestingly, we observed a better outcome for transformed DLBCL than de-novo DLBCL (24-month OS: 60% versus 45%, p=0.008). Notably, the 24-month non-relapse mortality was superimposable in HGBL and DLBCL pts (11% vs 11%, p=0.830). In the univariable logistic model, any grade CRS and ICANS (but not severe grade) were significantly higher in HGBL compared to DLBCL [CRS 92% vs 82%, odds ratio (OR) 0.37, (p=0.022); ICANS 35% vs 19%, OR 0.43, (p=0.005)]. We conducted a weighted comparison analysis on 132 pts (n=66 HGBL, n=66 DLBCL) to assess the impact of biological subtype on outcomes. The 24-month weighted PFS and OS were not significantly different between HGBL and DLBCL [PFS: 35% vs 31%, weighted log-rank p=0.937; OS: 39% vs 44%, weighted log-rank p=0.147]. Similarly, no differences were observed in weighted logistic regression for CRS and ICANS of any grade in the two groups (weighted p-values 0.112 and 0.075, respectively). A total of 234 pts (56%) experienced PD following CAR T-cells: 176 (75%) were treated with salvage therapy, including bispecific antibodies in 57 (32%). Following CAR T-cells failure, DLBCL pts had a better outcome than those diagnosed with HGBL (1-year post-relapse OS: 33% vs 16%, p=0.028). In univariable Cox models for OS following CAR T-cells therapy failure, pts treated with salvage and those affected by DLBCL had a better prognosis (HR=0.30, p<0.001; HR=0.64, p=0.038).

Conclusions: Our weighted comparison study showed that CAR T-cells therapy has similar efficacy in HGBL and DLBCL with an acceptable toxicity profile. Post-relapse OS was significantly lower in pts affected by HGBL compared to those with DLBCL due to inferior efficacy of salvage therapies. Higher PFS and OS may be expected using CAR T-cells therapy in the second line.

Disclosures: Dodero: gilled: Research Funding. Tisi: Incyte: Speakers Bureau; Lilly: Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees; Novatis: Membership on an entity's Board of Directors or advisory committees; Jansenn: Speakers Bureau; Beigene: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Gylead Science: Membership on an entity's Board of Directors or advisory committees. Chiappella: IDEOGEN: Honoraria; GILEAD-SCIENCES: Honoraria; ASTRAZENECA: Honoraria; INCYTE: Honoraria; JANNSEN-CILAG: Honoraria; NOVARTIS: Honoraria; TAKEDA: Honoraria; ROCHE: Honoraria. Botto: TAKEDA: Speakers Bureau. Barbui: Pierre Fabre: Honoraria, Other: transport and accomodation to EHA 2024, Speakers Bureau; Roche: Honoraria; Incyte: Speakers Bureau. Di Rocco: ROCHE: Honoraria, Speakers Bureau; NOVARTIS: Speakers Bureau; GILEAD: Honoraria, Speakers Bureau; JANSSEN: Honoraria; ABBVIE: Honoraria; TAKEDA: Speakers Bureau; INCYTE: Speakers Bureau. Zinzani: TAKEDA: 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; CELLTRION: 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; SERVIER: 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; EUSAPHARMA: Consultancy, 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; NOVARTIS: 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; MSD: Consultancy, 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; KYOWA KIRIN: 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; BMS: 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; SECURA BIO: Membership on an entity's Board of Directors or advisory committees. Corradini: Bristol Myers Squibb: Other: Support for travel and accommodations; SOBI: Other: Honoraria (for consultancy, participation in advisory boards, or lectures); Sanofi: Other: Honoraria (for consultancy, participation in advisory boards, or lectures); Roche: Other: Honoraria (for consultancy, participation in advisory boards, or lectures); support for travel and accommodations; Pfizer: Other: Honoraria (for consultancy, participation in advisory boards, or lectures); Novartis: Other: Honoraria (for consultancy, participation in advisory boards, or lectures); support for travel and accommodations; Kyowa Kirin: Other: Honoraria (for consultancy, participation in advisory boards, or lectures); Janssen: Other: Honoraria (for consultancy, participation in advisory boards, or lectures); support for travel and accommodations; Incyte: Other: Honoraria (for consultancy, participation in advisory boards, or lectures); GlaxoSmithKline: Other: Honoraria (for consultancy, participation in advisory boards, or lectures); Gilead/Kite: Other: Honoraria (for consultancy, participation in advisory boards, or lectures); support for travel and accommodations; Daiichi Sankyo: Other: Honoraria (for consultancy, participation in advisory boards, or lectures); Celgene: Other: Honoraria (for consultancy, participation in advisory boards, or lectures); support for travel and accommodations; Amgen: Other: Honoraria (for consultancy, participation in advisory boards, or lectures); support for travel and accommodations; AbbVie: Other: Honoraria (for consultancy, participation in advisory boards, or lectures); support for travel and accommodations; Takeda: Other: Honoraria (for consultancy, participation in advisory boards, or lectures); support for travel and accommodations.

*signifies non-member of ASH