Transfusion needs after CAR T-cell therapy for large B-cell lymphoma: predictive factors and outcome. A DESCAR-T study

Samuel Vic (1) , Jean-Baptiste Thibert (2) , Emmanuel Bachy (3) , Guillaume Cartron (4) , Thomas Gastinne (5) , Franck Morschhauser (6) , Fabien Le Bras (7) , Krimo Bouabdallah (8) , Fabien Despas (9) , Jacques-Olivier Bay (10) , Marie-Thérèse Rubio (11) , Mohamad Mohty (12) , René-Olivier Casasnovas (13) , Sylvain Choquet (14) , Cristina Castilla-Llorente (15) , Stéphanie Guidez (16) , Michael Loschi (17) , Blandine Guffroy (18) , Sylvain Carras (19) , Laurianne Drieu La Rochelle (20) , M Guillet (3) , Roch Houot (21)

1 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
2 EFS Bretagne - Etablissement français du sang [Rennes]
3 HCL - Hospices Civils de Lyon
4 IGMM - Institut de Génétique Moléculaire de Montpellier
5 CHU Nantes - Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
6 Université de Lille
7 Hôpital Henri Mondor
8 CHU Pessac
9 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
10 CHU Clermont-Ferrand
11 CHRU Nancy - Centre Hospitalier Régional Universitaire de Nancy
12 CRSA - Centre de Recherche Saint-Antoine
13 CHU Dijon - Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand
14 CHU Pitié-Salpêtrière [AP-HP]
15 IGR - Institut Gustave Roussy
16 CHU de Poitiers [La Milétrie] - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
17 CHU Nice - Centre Hospitalier Universitaire de Nice
18 ICANS - Institut de Cancérologie de Strasbourg Europe
19 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
20 CHRU Tours - Centre Hospitalier Régional Universitaire de Tours
21 MOBIDIC - Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer

Chimeric antigen receptor (CAR) T-cells targeting CD19 have been approved for the treatment of relapse/refractory large B-cell lymphoma. Hematotoxicity is the most frequent CAR T-cell-related adverse event. Transfusion support is a surrogate marker of severe cytopenias. Transfusion impacts patients’ quality of life, presents specific toxicities and is known to affect immunity through the so-called transfusion-related immunomodulation, that may impact CAR T-cell efficacy. We analyzed data from 671 patients from the French DESCAR-T registry for whom exhaustive transfusion data were available. Overall, 401 (59.8%) and 378 (56.3%) patients were transfused in the 6-month period before and after CAR T-cell, respectively. The number of transfused patients and the mean number of transfused products increased during the 6-month period before CAR-T, peaked during the first month after infusion (early phase) and decreased over time. Predictive factors for transfusion at the early phase were age > 60 years, ECOG PS ≥2, treatment with axi-cel, pre-CAR T-cell transfusions and CAR-HEMATOTOX score ≥ 2. Predictive factors for late transfusion (between 1 and 6 months after infusion) were pre-CAR T-cell transfusions, CAR-HEMATOTOX score ≥ 2, ICANS ≥ 3 (for red blood cells [RBC] transfusion) and tocilizumab use (for platelets transfusion). Early transfusions and late platelets (but not RBC) transfusions were associated with a shorter progression-free survival and overall survival. Lymphoma-related mortality and non-relapse mortality were both increased in the transfused population. Our data shed light on the mechanisms of early and late cytopenia, and on the potential impact of transfusions on CAR T-cell efficacy and toxicity.

Mots clés: CAR T-cells; large B-cell lymphoma; transfusion; cytopenia

Domaines: Sciences du Vivant [q-bio]

Samuel Vic, Jean-Baptiste Thibert, Emmanuel Bachy, Guillaume Cartron, Thomas Gastinne, et al.. Transfusion needs after CAR T-cell therapy for large B-cell lymphoma: predictive factors and outcome. A DESCAR-T study. Blood Advances, 2024, Blood Advances, 8 (6), pp.1573-1585. ⟨10.1182/bloodadvances.2023011727⟩. ⟨hal-04399634⟩