Outcomes of patients with aggressive B-cell lymphoma after failure of anti-CD19 CAR T-cell therapy: a DESCAR-T analysis

Roberta Di Blasi (1) , Steven Le Gouill (2) , Emmanuel Bachy (3) , Guillaume Cartron (4) , David Beauvais , Fabien Le Bras , François-Xavier Gros , Sylvain Choquet , Pierre Bories , Pierre Feugier , Olivier Casasnovas , Jacques Olivier Bay , Mohamad Mohty , Magalie Joris , Thomas Gastinne , Pierre Sesques , Jean-Jacques Tudesq , Laetitia Vercellino , Franck Morschhauser , Elodie Gat (5) , Florence Broussais (6) , Roch Houot (7, 8) , Catherine Thieblemont (1)

1 AP-HP - Hopital Saint-Louis [AP-HP]
2 Institut Curie [Paris]
3 HCL - Hospices Civils de Lyon
4 IGMM - Institut de Génétique Moléculaire de Montpellier
5 CALYM - Institut Carnot Lymphome
6 LYSARC - The Lymphoma Academic Research Organisation [Lyon]
7 CHU Pontchaillou [Rennes]
8 MOBIDIC - Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer

Anti-CD19 chimeric antigen receptor (CAR) T-cells represent a major advance in the treatment of relapsed/refractory aggressive B-cell lymphomas. However, a significant number of patients experience failure. Among 550 patients registered in the French registry DESCAR-T, 238 (43.3%) experienced progression/relapse, with a median follow-up of 7.9 months. At registration, 57.0% of patients presented an age-adjusted International Prognostic Index of 2 to 3, 18.9% had Eastern Cooperative Oncology Group performance status ≥2, 57.1% received >3 lines of treatment prior to receiving CAR T-cells, and 87.8% received bridging therapy. At infusion, 66% of patients presented progressive disease, and 38.9% had high lactate dehydrogenase (LDH). Failure after CAR T-cell treatment occurred after a median of 2.7 months (range: 0.2-21.5). Fifty-four patients (22.7%) presented very early failure (day [D] 0-D30); 102 (42.9%) had early failure (D31-D90), and 82 (34.5%) had late (>D90) failure. After failure, 154 patients (64%) received salvage treatment: 38.3% received lenalidomide, 7.1% bispecific antibodies, 21.4% targeted treatment, 11% radiotherapy, and 20% immunochemotherapy with various regimens. Median progression-free survival was 2.8 months, and median overall survival (OS) was 5.2 months. Median OS for patients failing during D0-D30 vs after D30 was 1.7 vs 3.0 months, respectively (P = .0001). Overall, 47.9% of patients were alive at 6 months, but only 18.9% were alive after very early failure. In multivariate analysis, predictors of OS were high LDH at infusion, time to CAR-T failure

Domains: Life Sciences [q-bio]; Cancer

Roberta Di Blasi, Steven Le Gouill, Emmanuel Bachy, Guillaume Cartron, David Beauvais, et al.. Outcomes of patients with aggressive B-cell lymphoma after failure of anti-CD19 CAR T-cell therapy: a DESCAR-T analysis. Blood, 2022, 140 (24), pp.2584-2593. ⟨10.1182/blood.2022016945⟩. ⟨hal-03903472⟩