Laura M Moser, Martin Hutter, Martina Ahlmann, Anna Alonso-Saladrigues, Andishe Attarbaschi, Francis A Ayuk, Claudia D Baldus, Adriana Balduzzi, Halvard Bonig, Jean-Pierre Bourquin, Jochen Buechner, Veit L Buecklein, Saskia Burridge, Friso G Calkoen, Gunnar Cario, Barbara De Moerloose, Gustavo de Oliveira Canedo, Marie-Emilie Dourthe, Tobias Feuchtinger, Anna Füreder, Julia Hauer, Marianne Ifversen, Andrea Jarisch, Krzysztof Kalwak, Jan-Henning Klusmann, Guido Kobbe, Christian Koenecke, Annette Künkele, Roland Meisel, Pietro Merli, Monika Mielcarek-Siedziuk, Fabian Müller, Ingo Müller, Sara Napolitano, Macarena Oporto Espuelas, Olaf Penack, Florence Rabian, Claudia Rossig, Martin G Sauer, Paul G Schlegel, Arend von Stackelberg, Brigitte Strahm, Semjon Willier, Peter Bader, Susana Rives, Nicolas Boissel, Franco Locatelli, Sara Ghorashian, André Baruchel
This multicenter real-world study identifies critical determinants of outcome for tisagenlecleucel (tisa-cel) in treating post-HSCT relapse in 220 children/young adults with B-ALL from 31 European centers. Median follow-up was 30.0 months, with a 43.6% 2-year event-free survival (EFS), 67.2% overall-survival (OS), and 57.1% incidence of CAR-T failure. CAR-T for relapse after transplant from a matched sibling donor (MSD) compared to alternative donors was associated with lower 2-year-OS (MSD 59.1%, mismatched donor MMD 80.2%, matched family/unrelated donor MFD/MUD 68.3%, p = 0.046). Two-year incidence of CAR-T failure was highest for MSD (MSD 73.8%, MFD/MUD 49.7%, MMD 52.2%, p = 0.006). Patients who had relapsed early (< 6 months post HSCT) showed inferior 2-year-EFS (23.7%) and OS (47.2%) compared to patients with late relapse, ≥ 6 months after HSCT (EFS 49.8%, p = 0.001; OS 73.9%, p < 0.001). Early relapse was associated with a higher incidence of CAR-T failure and relapse after tisa-cel, particularly CD19+ relapses. Outcomes correlated with disease burden at lymphodepletion: 2-year-OS was 81.7% for MRD-, 69.2% for MRD+, and 55.2% for patients in non-remission (p = 0.003), with incidence of CAR-T failure highest in non-remission. Prior transplant from an MSD, early post-HSCT relapse, and disease burden at lymphodepletion identify patients at increased risk of CAR-T failure after HSCT.