Laura M. Moser, Martin Hutter, Martina Ahlmann, Anna Alonso‐Saladrigues, Andishe Attarbaschi, Francis Ayuk, Claudia D. Baldus, Adriana Balduzzi, Halvard Bönig, Jean‐Pierre Bourquin, Jochen Buechner, Veit Bücklein, Saskia Burridge, Friso Calkoen, Gunnar Cario, Barbara De Moerloose, Gustavo de Oliveira Canedo, Marie-Emilie Dourthe, Tobias Feuchtinger, Anna Füreder, Julia Hauer, Marianne Ifversen, Andrea Jarisch, Krzysztof Kałwak, 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 Rössig, 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
Abstract 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.