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

ABSTRACT: 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 affects patients' quality of life, presents specific toxicities, and is known to affect immunity through the so-called transfusion-related immunomodulation that may affect 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 received transfusion in the 6-month period before and after CAR T-cell infusion, respectively. The number of patients receiving transfusion and the mean number of transfused products increased during the 6-month period before CAR T-cell infusion, 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 axicabtagene ciloleucel, 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 nonrelapse 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.

Disease-specific outcomes after chimeric antigen receptor T-cell therapy.

We compared outcomes of patients with B-cell malignancies treated in clinical trials with the same CD19 chimeric antigen receptor (CAR) T-cells across different indications, including B-cell acute lymphoblastic leukaemia (B-ALL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL) and follicular lymphoma (FL). We found that for a given CAR T-cell, efficacy and toxicity varied depending on the disease. Overall, we found a low rate of primary resistance in FL, MCL and B-ALL compared with DLBCL. Acute toxicities (cytokine release syndrome and ICANS) appeared to be significantly less severe in FL compared with more aggressive diseases, such as B-ALL, DLBCL and MCL. These observations suggest that each B-cell malignancy harbours specific biology, which may interact differently with CAR T-cell therapy. Thus, CAR T-cells may be tailored differently depending on the type of B-cell malignancy to optimise their efficacy and safety.

Transplant-ineligible but chimeric antigen receptor T-cells eligible: a real and relevant population.

Autologous stem cell transplantation (ASCT) and chimeric antigen receptor (CAR) T-cells are two therapeutic options for relapsed/refractory diffuse large B-cell lymphoma. Both are intensive and potentially curative therapies but differ in their efficacy and toxicity. ASCT may be offered to 'fit' patients (i.e. usually young with limited comorbidities) with chemosensitive disease. On the other hand, real world studies have shown that CAR T-cells may be safely administered to less fit and older patients. Thus, there is a potentially significant population of patients who may be offered CAR T-cell therapy despite not being eligible for ASCT. As the relative role of ASCT and CAR T-cells evolves, recognising and defining this population may be increasingly relevant. Here, we review criteria which may help identify this 'ASCT-ineligible but CAR T-cells eligible' population of patients.