Comparison of axicabtagene ciloleucel to standard regimens as second line treatment for large B cell lymphoma in real life: A lysa study from descar-T and realysa registries

Abstract IntroductionThe treatment landscape of early relapsed/refractory (R/R) large B-cell lymphoma (LBCL) has been transformed by anti-CD19 CAR T-cells. In ZUMA-7, transplant-intended early R/R LBCL patients treated with axicabtagene ciloleucel (axi-cel) had longer event-free survival (EFS) than those receiving standard salvage chemoimmunotherapy (SOC). At 47.2 months' median follow-up, median overall survival (OS) was not reached for axi-cel and was 31.1 months for SOC; estimated 4-year OS was 54.6% and 46.0%, respectively (Locke NEJM 2022, Westin NEJM 2023). Since approval, axi-cel has become the predominant CAR T therapy in France for 2L treatment since July 2022. However, access remains uneven, as CAR T-cell therapy is not universally available. In this context, we performed a retrospective multicenter study to assess real-world outcomes of early R/R LBCL patients treated with 2L axi-cel versus SOC. MethodologyTo quantify the effect of intention to receive axi-cel versus SOC as 2L therapy in early R/R LBCL, we analyzed individual-level data from two French studies: the REALYSA cohort (SOC) and DESCAR-T registry (axi-cel). Adults (≥18 years) with LBCL, high-grade B-cell lymphoma (HGBL), or primary mediastinal B-cell lymphoma (PMBL) refractory to first-line immunochemotherapy or relapsed within 12 months were included, regardless of transplant eligibility. To minimize selection bias, we included REALYSA patients treated in 2L before axi-cel's 2L approval (<July 2022), and axi-cel cases treated in 2L from July 2022 to December 2023 with at least 12 months' follow-up. Time-to-event outcomes were measured from the date of strategy decision (axi-cel) or 2L start (SOC). Groups were balanced with propensity scores (PS) and stabilized inverse probability weighting (sIPTW) using age (spline), sex, histology, stage, ECOG performance status (PS), LDH, and time from diagnosis to 2L. Outcomes were EFS (to progression, new therapy, or death) and OS. The weighted Kaplan–Meier estimator was used. ResultsWe identified 659 eligible patients: 465 received axi-cel, 194 SOC. After excluding those with missing covariate data, the complete case analysis included 356 axi-cel and 132 SOC patients. At baseline: most had advanced stage (82% axi-cel, 80% SOC), and primary refractory disease (77.5% axi-cel, 77.3% SOC). Mean time from diagnosis to 2L was similar (0.63 years axi-cel, 0.64 years SOC). SOC patients were older (mean 65.9 vs 58.6 years). HGBL (18.2% vs 5.1%) and PMBL (6.1% vs 3.7%) were more frequent in SOC, and ECOG PS ≥2 was higher in SOC (30% vs 12%). SOC regimens were mainly platinum-based (R-DHAC/Ox 38%, R-GemOx 21%). In the SOC arm, 35.6% were <65 years (vs 57.6% axi-cel); 10.8% underwent autologous transplant (24.6% among those ≤65 years). Median follow-up was 1.2 years (axi-cel) versus 2.8 years (SOC). After PS-weighting, baseline variables were well-balanced (standardized mean differences <0.1). EFS at 1 year favored axi-cel: 46% vs 16% (weighted log-rank p<0.001). OS showed a trend favoring axi-cel but was not statistically significant (1-year OS 64% vs 57%, p=0.46). In SOC, 62.4% (n=121/194) received third-line therapy, mostly CAR T-cells (n=49/121, 40.5%) or salvage chemotherapy (n=43/121, 35.5%); lenalidomide-based regimens were given in 18.2% (n=22/121), and only 2 patients received bispecifics. ConclusionIn this large French cohort, including both transplant-eligible and ineligible early R/R LBCL patients, a clear EFS benefit was observed with axi-cel, consistent with ZUMA-7 results. However, this did not translate into a significant OS benefit, possibly due to short follow-up or third-line CAR T use in the SOC arm. Indeed, CAR T was the most frequent third-line option after SOC and may have impacted OS. Further analysis is needed to clarify the optimal role of CAR T-cell therapy in R/R LBCL, including medico-economic evaluation. Ongoing work will address missing data with multiple imputations for improved estimates.

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Blood
Published
2025-11-03
DOI
https://doi.org/10.1182/blood-2025-2764
Primary Topic
CAR-T cell therapy research
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article
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article

Comparison of axicabtagene ciloleucel to standard regimens as second line treatment for large B cell lymphoma in real life: A lysa study from descar-T and realysa registries

Elodie Gat, Gabriel Brisou, Blandine Guffroy, Aline Schmidt et al.
Blood
CAR-T cell therapy research
article

Comparison of axicabtagene ciloleucel to standard regimens as second line treatment for large B cell lymphoma in real life: A lysa study from descar-T and realysa registries

Elodie Gat, Gabriel Brisou, Blandine Guffroy, Aline Schmidt, Aurélien Belot, Fabrice Jardin, Michael L. Loschi, Sylvain Choquet, Roberta Di Blasi, Fanny Cherblanc, Pierre Bories, Luc‐Matthieu Fornecker, Adrien Chauchet, Corinne Haïoun, Roch Houot, Pauline Lionne, Amandine Durand, Cécile Leyronnas, Cristina Castilla‐Llorente, Stéphanie Guidez, Laure Lebras, Franck Morschhauser, Emmanuel Bachy, Gandhi Laurent Damaj, Gaëlle Labouré, Olivier Hermine, Thomas Gastinne, Krimo Bouabdallah, Christophe Fruchart, Fontanet Bijou, Bernard Drénou, Antoine Bonnet, Sylvain Carras, Rémy Duléry, Laure Vincent, Guillaume Cartron, Laura Herbreteau, Benoît Tessoulin, Fabien Le Bras, Hervé Ghesquières, Cédric Rossi, Nadine Morineau, Justine Decroocq, François‐Xavier Gros, Marie‐Thérèse Rubio, Olivier Fitoussi, Julie Abraham, Sandy Amorim, Sophie Dennetiere, Ludovic Fouillet, Laurianne Drieu La Rochelle, Jacques‐Olivier Bay, Gaëlle Olivier, Magalie Joris
article en

Abstract

Abstract IntroductionThe treatment landscape of early relapsed/refractory (R/R) large B-cell lymphoma (LBCL) has been transformed by anti-CD19 CAR T-cells. In ZUMA-7, transplant-intended early R/R LBCL patients treated with axicabtagene ciloleucel (axi-cel) had longer event-free survival (EFS) than those receiving standard salvage chemoimmunotherapy (SOC). At 47.2 months' median follow-up, median overall survival (OS) was not reached for axi-cel and was 31.1 months for SOC; estimated 4-year OS was 54.6% and 46.0%, respectively (Locke NEJM 2022, Westin NEJM 2023). Since approval, axi-cel has become the predominant CAR T therapy in France for 2L treatment since July 2022. However, access remains uneven, as CAR T-cell therapy is not universally available. In this context, we performed a retrospective multicenter study to assess real-world outcomes of early R/R LBCL patients treated with 2L axi-cel versus SOC. MethodologyTo quantify the effect of intention to receive axi-cel versus SOC as 2L therapy in early R/R LBCL, we analyzed individual-level data from two French studies: the REALYSA cohort (SOC) and DESCAR-T registry (axi-cel). Adults (≥18 years) with LBCL, high-grade B-cell lymphoma (HGBL), or primary mediastinal B-cell lymphoma (PMBL) refractory to first-line immunochemotherapy or relapsed within 12 months were included, regardless of transplant eligibility. To minimize selection bias, we included REALYSA patients treated in 2L before axi-cel's 2L approval (<July 2022), and axi-cel cases treated in 2L from July 2022 to December 2023 with at least 12 months' follow-up. Time-to-event outcomes were measured from the date of strategy decision (axi-cel) or 2L start (SOC). Groups were balanced with propensity scores (PS) and stabilized inverse probability weighting (sIPTW) using age (spline), sex, histology, stage, ECOG performance status (PS), LDH, and time from diagnosis to 2L. Outcomes were EFS (to progression, new therapy, or death) and OS. The weighted Kaplan–Meier estimator was used. ResultsWe identified 659 eligible patients: 465 received axi-cel, 194 SOC. After excluding those with missing covariate data, the complete case analysis included 356 axi-cel and 132 SOC patients. At baseline: most had advanced stage (82% axi-cel, 80% SOC), and primary refractory disease (77.5% axi-cel, 77.3% SOC). Mean time from diagnosis to 2L was similar (0.63 years axi-cel, 0.64 years SOC). SOC patients were older (mean 65.9 vs 58.6 years). HGBL (18.2% vs 5.1%) and PMBL (6.1% vs 3.7%) were more frequent in SOC, and ECOG PS ≥2 was higher in SOC (30% vs 12%). SOC regimens were mainly platinum-based (R-DHAC/Ox 38%, R-GemOx 21%). In the SOC arm, 35.6% were <65 years (vs 57.6% axi-cel); 10.8% underwent autologous transplant (24.6% among those ≤65 years). Median follow-up was 1.2 years (axi-cel) versus 2.8 years (SOC). After PS-weighting, baseline variables were well-balanced (standardized mean differences <0.1). EFS at 1 year favored axi-cel: 46% vs 16% (weighted log-rank p<0.001). OS showed a trend favoring axi-cel but was not statistically significant (1-year OS 64% vs 57%, p=0.46). In SOC, 62.4% (n=121/194) received third-line therapy, mostly CAR T-cells (n=49/121, 40.5%) or salvage chemotherapy (n=43/121, 35.5%); lenalidomide-based regimens were given in 18.2% (n=22/121), and only 2 patients received bispecifics. ConclusionIn this large French cohort, including both transplant-eligible and ineligible early R/R LBCL patients, a clear EFS benefit was observed with axi-cel, consistent with ZUMA-7 results. However, this did not translate into a significant OS benefit, possibly due to short follow-up or third-line CAR T use in the SOC arm. Indeed, CAR T was the most frequent third-line option after SOC and may have impacted OS. Further analysis is needed to clarify the optimal role of CAR T-cell therapy in R/R LBCL, including medico-economic evaluation. Ongoing work will address missing data with multiple imputations for improved estimates.

BloodVol. 146(Supplement 1)
Université Claude Bernard Lyon 1 (FR), LeTourneau University (US), Hôpital Necker-Enfants Malades (FR), Sciences Po Bordeaux (FR), Université de Bordeaux (FR), Université de Bourgogne (FR), Université de Montpellier (FR), Université Côte d'Azur (FR), Institut Gustave Roussy (FR), Centre Hospitalier Universitaire de Lille (FR), Centre Hospitalier Universitaire de Nice (FR), Centre Hospitalier Universitaire Henri-Mondor (FR), Université Rennes 2 (FR), Université de Poitiers (FR), Sorbonne Université (FR), Institut de Chimie de Nice (FR), Centre Hospitalier de Roubaix (FR), Centre Hospitalier Universitaire de Besançon (FR), Institut de Cancérologie Strasbourg (FR), Laboratoire d'Economie Appliquée de Grenoble (FR), Hôpital Cochin (FR), Centre Hospitalier Universitaire de Tours (FR), Communauté urbaine de Lyon (FR), Centre Hospitalier Universitaire Amiens-Picardie (FR), Assistance Publique – Hôpitaux de Paris (FR), Institut universitaire du cancer de Toulouse Oncopole (FR), Hôpital Bretonneau (FR), Centre Hospitalier Régional et Universitaire de Nancy (FR), Hôpital Saint-Antoine (FR), Centre d’Investigation Clinique Innovation Technologique de Nancy (FR), Laboratoire d'Informatique de Grenoble (FR), Centre Léon Bérard (FR), The Lymphoma Academic Research Organisation (FR), Centre Hospitalier de Niort (FR), Laboratoire de Physique Corpusculaire de Caen (FR), Centre hospitalier Bretagne Atlantique (FR), Centre Hospitalier Universitaire de Caen Normandie (FR), Polyclinique Bordeaux Nord Aquitaine (FR), CHU Dijon Bourgogne (FR), Centre Hospitalier de Mulhouse (FR), Centre Hospitalier Universitaire de Limoges (FR), Health Services and Performance Research Laboratory (FR), Pitié-Salpêtrière Hospital (FR), Centre d'Investigation Clinique de Nantes (FR), Centre Hospitalier Universitaire de Clermont-Ferrand (FR), Hôpitaux Universitaires Henri-Mondor (FR), Montpellier Business School (FR), Centre Hospitalier Régional Universitaire de Brest (FR), Institut Bergonié (FR), Centre Hospitalier d'Arras (FR), Observatoire des Sciences de l’Univers Terre Homme Environnement Temps Astronomie (FR), Laboratoire National Henri Becquerel (FR), Hôpital Saint-Louis (FR), Centre Hospitalier Départemental Vendée (FR), Services déconcentrés d'appui à la recherche Occitanie-Montpellier (FR), Institut Paoli-Calmettes (FR), Centre Hospitalier Universitaire de Saint-Étienne (FR), Institut Polytechnique de Bordeaux (FR), Hôpital Saint-Vincent-de-Paul (FR), Yves Rocher (France) (FR), Université d'Angers (FR), Université de Rennes (FR), Université de Limoges (FR), Grenoble Ecole de Management (FR), Université Grenoble Alpes (FR), Université de Caen Normandie (FR)
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CAR-T cell therapy research
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