Comparison of axi-cel versus liso-cel as 2nd line therapy for relapsed/refractory large B-cell lymphoma in real-life: A lysa study from the descar-T registry
Year: 2025
Type: conference-abstract
Abstract: Background Axicabtagene ciloleucel (axi-cel) and Lisocabtagene maraleucel (liso-cel), two anti-CD19 CAR T-cells, have been approved as 2nd line (2L) treatment in relapsed/refractory (R/R) large B-cell lymphoma (LBCL) for patients progressing within 12 months of first-line chemo-immunotherapy, based on the ZUMA-7 and TRANSFORM trials, respectively. In the ZUMA 7 trial, axi-cel demonstrated a median event-free survival (EFS) of 10.8 months and an estimated 4-year overall survival (OS) of 54.6% (Locke NEJM 2022, Westin NEJM 2023). In the TRANSFORM trial, liso-cel was associated with a median EFS of 29.5 months with a 3-year OS rate of 62.8% (Abramson Blood 2023; Kamdar ASCO 2024). Given the absence of a randomized comparison between axi-cel and liso-cel as 2L treatment for R/R LBCL, we conducted a comparative analysis of patients treated in France with these two products since their approval. Methods All data were collected through the French DESCAR-T registry designed by the LYSA/LYSARC to collect real-life data. Inclusion criteria were diagnosis of LBCL, 1 prior line of treatment, at least 6 months of follow up after infusion (Leukapheresis performed before September 2024). We conducted a comparison of axi-cel and liso-cel in a large cohort of 2L R/R LBCL patients treated in France using a propensity score (PS). Multiple imputations were used to handle missing variables. We used the stabilized inverse probability weighting (sIPTW) method to balance axi-cel and liso-cel populations. The PS was calculated for each patient with a logistic regression using the following variables: age, sex, refractory status at 1st line completion, time between 1st treatment end and leukapheresis; at leukapheresis, performance status (ECOG PS), Ann Arbor stage, center experience (time from 1st center leukapheresis and leukapheresis of patient), LBCL histology, LDH level; and at infusion, vein-to-vein time, response to bridging therapy, ECOG PS, LDH, CRP. Endpoints were best ORR and CRR (Lugano 2014), progression-free survival (PFS), OS, and toxicities (CRS, ICANS, intensive care unit transfer). OS and PFS were evaluated from leukapheresis. Results An initial cohort of 805 patients with LBCL (LBCL NOS n=663, PMBL n=38, transformed indolent NHL n=104) treated with axi-cel (n=663) or liso-cel (n=142) in 2L was analyzed. Most were male (63%) with refractory disease (73%). Characteristics were imbalanced regarding age (median 68y liso-cel vs 62y axi-cel), LBCL histology (PMBL 12% liso-cel vs 3% axi-cel), Ann Arbor stage (stage III/IV 69% liso-cel vs 76% axi-cel), center experience (more in liso-cel arm), and time from last treatment to infusion, longer with liso-cel (median 110 days liso-cel vs 90 days axi-cel). After sIPTW using axi-cel pts as reference, outcome was compared in a pseudo-population with balanced confounders: 647 intended for axi-cel and 155 for liso-cel, corresponding to 600 infused with axi-cel, 127 with liso-cel. No significant residual differences in baseline characteristics were observed (standard mean differences <0.1). Median follow-up from leukapheresis was 12.9 months for axi-cel, 7.7 months for liso-cel. OS and PFS were not significantly different between products in the intention to treat population, nor when analyzed from infusion. Regarding best CRR, no significant differences were observed (62.6% axi-cel vs 65.8% liso-cel, P=0.5). Best ORR was higher with liso-cel (79.8% axi-cel vs 90% liso-cel, P=0.008). Concerning toxicity, grade 3+ CRS was infrequent in both groups (5.1% axi-cel vs 3.1% liso-cel, P=0.346), but CRS of any grade was more frequent with axi-cel (93.9% vs 50.8%, P<0.001). Neurotoxicity and severe neurotoxicity were higher with axi-cel (grade 3+ ICANS 17.6% vs 0.2%, P<0.001). ICU transfers were more frequent after axi-cel (22.4% vs 5.3%, P<0.001). Conclusion After PS-weighting in a large French population with CAR T-cell therapy for 2L LBCL, there was no significant OS or PFS difference between axi-cel and liso-cel. However, axi-cel had a greater incidence of severe neurotoxicity. These results require confirmation in a larger liso-cel cohort with longer follow-up. Baseline differences reveal selection bias regarding CAR-T choice; liso-cel being more often proposed to older, frailer patients, able to wait longer for infusion. Axi-cel may be more effective in a subgroup with rapidly progressing, primary-refractory disease; further analyses are needed to define the optimal place of each product.
Source: Blood
Authors: Gabriel Brisou, Emmanuel Bachy, Elodie Gat, Guillaume Cartron, Roch Houot, Pierre Sesques, François-Xavier Gros, Roberta Di Blasi, Fabien Le Bras, Cristina Castilla-Llorente, Pierre Bories, Laurianne Drieu La Rochelle, Michael Loschi, Franck Morschhauser, Cedric Rossi, Stephanie Guidez, Sylvain Choquet, Laure Ricard, Fabrice Jardin, Marie-Thérèse Rubio, Aline Schmidt, Gandhi Damaj, Sylvain Carras, Jacques-Olivier Bay, Laure Lebras, Magalie Joris, Laura Herbreteau, Julie Abraham, Ludovic Fouillet, Adrien Chauchet, Jean-Valère Malfuson, Olivier Hermine, Blandine Guffroy, Justine Decroocq, Steven Le Gouill, Benoit Tessoulin
Institutions: Institut Paoli-Calmettes, Hospices Civils de Lyon, The Lymphoma Academic Research Organisation, Centre Hospitalier Universitaire de Montpellier, Centre Hospitalier Universitaire de Rennes, Centre Hospitalier Universitaire de Bordeaux, Assistance Publique – Hôpitaux de Paris, Hôpital Saint-Louis, Hôpitaux Universitaires Henri-Mondor, Institut Gustave Roussy, Institut universitaire du cancer de Toulouse Oncopole, Centre Hospitalier Universitaire de Tours, Centre Hospitalier Universitaire de Nice, Centre Hospitalier Universitaire de Lille, CHU Dijon Bourgogne, Centre Hospitalier Universitaire de Poitiers, Pitié-Salpêtrière Hospital, Hôpital Saint-Antoine, Centre Henri Becquerel, Centre Hospitalier Régional et Universitaire de Nancy, Centre Hospitalier Universitaire d'Angers, Centre Hospitalier Universitaire de Caen Normandie, Centre Hospitalier Universitaire de Clermont-Ferrand, Centre Léon Bérard, Centre Hospitalier Universitaire Amiens-Picardie, Centre Hospitalier Universitaire de Limoges, Centre Hospitalier Universitaire de Saint-Étienne, Centre Hospitalier Universitaire de Besançon, Hôpital d'instruction des Armées Percy, Hôpital Necker-Enfants Malades, Institut de Cancérologie Strasbourg, Hôpital Cochin, Institut Curie, Centre Hospitalier Universitaire de Nantes
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4417017802