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3124 Early Progressions of Undetermined Significance (EPUS) in the Month Following CAR-T Cells for B-Cell NHL Is Mainly Related to PseudoprogressionClinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 627. Aggressive Lymphomas: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Biological therapies, Research, Lymphomas, Chimeric Antigen Receptor (CAR)-T Cell Therapies, B Cell lymphoma, Clinical Research, Diseases, Therapies, aggressive lymphoma, real-world evidence, Adverse Events, Lymphoid Malignancies
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Benoît Tisserand1*, Caroline Bret, PhD, PharmD2,3*, Yassine Al Tabaa, MD, PhD, PharmD4*, Sylvain Lamure, MD, PhD1,5*, Xavier Ayrignac, MD, PhD6*, Laura Platon, MD7*, Patrice Ceballos, MD1*, Ludovic Gabellier, MD, PhD1,5*, Jerome Moreaux, PhD2,8, Charles Herbaux, MD, PhD1,2*, Guillaume Cartron, MD, Ph-D9,10* and Jean-Jacques Tudesq, MD, MSc1*

1Clinical Hematology Department, Montpellier University Hospital, MONTPELLIER, France
2Institute of Human Genetics, CNRS UM UMR 9002, University of Montpellier, MONTPELLIER, France
3Dept. Biological Hematology, CHU Saint Eloi Hospital, MONTPELLIER, France
4Scintidoc Nuclear Medicine Center, Montpellier, France
5IGMM UMR 5535 CNRS UM, University of Montpellier, MONTPELLIER, France
6Neurology Department, Montpellier University Hospital, Montpellier, France
7Intensive Care Unit, Montpellier University Hospital, MONTPELLIER, France
8Laboratory for Monitoring Innovative Therapies, Department of Biological Hematology, Montpellier University Hospital, Montpellier, France
9Clinical Hematology Department, Montpellier University Hospital Center, Montpellier, France
10IGMM UMR 5535 CNRS UM, University of Montpellier, Montpellier, France

INTRODUCTION – Relapsed-refractory B-cell non-Hodgkin's lymphomas (R/R-B-NHL) treatment remains challenging. In this context, CAR T-cell therapy has shown sustained efficacy in 40-60% of patients. Early progressions and pseudo-progression have been described after CAR T-cell therapy, but data are scarce. This study aims to assess incidence, risk factors and outcomes of early progression in patients treated with CAR T-cells for R/R B-NHL.

PATIENTS & METHODS – All patients were consecutively treated at the University Hospital of Montpellier with a commercial CAR T-cells for R/R-B-NHL between December 2019 and June 2022 and included in the CARTBANK cohort (ID RCB: 2019-A03032-55, NCT04290000). Cases were retrospectively reviewed for early progression. No antitumor treatment was initiated before the day 28 evaluation. Early Progressions of Undetermined Significance (EPUS) were defined as either: self-reported symptom of lymphoma (possible EPUS), clinically assessed progression (probable), or measured through imaging procedure (highly probable) after CAR T-cell infusion and before day 28 (D28) post evaluation. Pseudo-progression was defined as EPUS with partial or complete response on D28 evaluation. On the contrary, hyper-progression was defined as EPUS with confirmed progression on D28 evaluation.

RESULTS – A total of 105 patients were included in the study, with a median age of 65 years (interquartile range: 55;70]) and 70% were male. Diffuse large B-cell lymphoma (DLBCL) was the most common histology (89%), followed by follicular lymphoma (6%) and mantle cell lymphoma (5%). Patients had received a median of 2 previous lines of anti-cancer therapy [2;3]. Axicabtagene-ciloleucel was used in 77% of the cases, tisagenlecleucel in 18%, and brexucabtagene-autoleucel in 5%.

Overall 18 patients (17%) had EPUS: 2 possible EPUS (11%), 6 (33%) probable EPUS and 10 (56%) highly probable EPUS (panel A). D28 evaluation revealed that most of EPUS were pseudo-progressions (n=13/18, 72%). Hyper-progression was observed in one patient (6%) and 4 patients (22%) died before first metabolic assessment and remained unclassified (panel B). The cause of death was suspected of progression for three of them and sepsis for one. All EPUS occurred before day 21 (median: 7 days [3;8]). Comparison of patients with and without EPUS showed that no clear risk factors for EPUS were identified. EPUS occurrence had no impact on PFS nor OS. The blood expansion of CAR-T cells and their level of exhaustion were monitored by multi-parametric flow cytometry. Regarding these pharmacokinetic parameters, no significant difference was obtained between patients with and without EPUS. Analysis of data regarding total metabolic volume is ongoing and will be presented.

DISCUSSION – In this cohort, EPUS is observed in 17% of patients after CAR T-cells infusion for R/R B-NHL. Most of EPUS are related to pseudo-progression. These results should be confirmed in a dedicated study. Thus, early treatment before first evaluation should be avoided.

Disclosures: Herbaux: AbbVie, F. Hoffmann-La Roche Ltd, AstraZeneca, Janssen: Honoraria; AbbVie, Takeda: Research Funding; Physician and professor of Hematology at academic center (CHU Montpellier France): Current Employment; AbbVie, F. Hoffmann-La Roche Ltd, AstraZeneca, Janssen: Consultancy. Cartron: Emercell: Consultancy; BMS: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Janssen: Honoraria; MabQi: Consultancy; Ownards Therapeutics: Consultancy; MedxCell: Consultancy; Novartis: Honoraria; AbbVie: Consultancy, Honoraria; Jansen, Gilead, Novartis, F. Hoffmann-La Roche Ltd, BMS, Abbvie: Honoraria; Gilead: Honoraria; MedxCell, Ownards Therapeutics, MabQi, Emercell, F. Hoffmann-La Roche Ltd, BMS, Abbvie: Consultancy; MabQi, Ownards Therapeutics, Abbvie, Roche, Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees. Tudesq: BMS/Celgene: Consultancy; Gilead/Kite: Honoraria.

*signifies non-member of ASH