Abstract
Simple SummaryB-cell non-Hodgkin lymphomas (NHL) include many diseases with distincts pathogenic mechanisms, prognoses and management. Most patients benefit generally from efficient therapies allowing cure or prolonged remission. However, when they are refractory or relapse after standard therapy, they harbor a poor prognosis. In last decades, numerous novel immunotherapies have been developed with the aim of redirecting T-cell specificity against tumor antigens. Latest data on CAR T-cells confirm their efficacy and their safety in this setting. In addition, trials with bispecific antibodies are also ongoing for these patients, with encouraging premiminary findings, whether before or after CAR T-cells treatment. Here, we review the main results of CAR T-cells and bispecific T-cell engagers studies in the B-cell non-Hodgkin lymphomas setting. These advances in immunotherapies have transformed diffuse large B-cell lymphomas prognosis and will process indolent NHL’s future. Results with such treatments could lead to a new standard of care for those patients who are often heavily pretreated.T-cell specificity can be redirected against tumor antigens either ex vivo using engineered chimeric antigen receptor (CAR) T-cells or in vivo by bridging natural T-cells and tumor cells with bispecific T-cell engager (TCE) antibodies. Currently, four CAR T-cells have been approved by the FDA for the treatment of B-cell lymphomas, including diffuse large B cell lymphomas (DLBCL), mantle cell lymphoma (MCL), and follicular lymphoma (FL). No TCE have yet been approved for the treatment of B-cell lymphomas. However, at least four of them are in clinical development and show promising activity. Here, we review the most recent advances of CAR T-cells and TCE in the treatment of B-cell lymphomas.
Highlights
B-cell non-Hodgkin lymphomas (B-NHL) benefit from efficient therapies allowing cure or prolonged remission in most patients
Four chimeric antigen receptor (CAR) T-cells—axicabtagene ciloleucel (Axi-cel, Yescarta®, Hoofddorp, The Netherlands), tisagenlecleucel (Tisa-cel, Kymriah®, Basel, Switzerland), lisocabtagene maraleucel (Liso-cel, Breyanzi®, Seattle, WA, US), and brexucabtagene autoleucel (Brexu-cel, Tecartus®, Hoofddorp, The Netherlands)—have been approved by the FDA for the treatment of B-cell lymphomas, including diffuse large B-cell lymphomas (DLBCL), mantle cell lymphoma (MCL), and follicular lymphoma (FL) (Table 1)
One from the ZUMA-1 study and another from the CIBMTR registry, demonstrated that CAR-T cell therapy was feasible in elderly patients, with similar efficacy and safety compared to younger patients [5,12,13]
Summary
B-cell non-Hodgkin lymphomas (B-NHL) benefit from efficient therapies allowing cure or prolonged remission in most patients. Novel therapies have been developed to mobilize and re-direct the immune system against malignant B-cells in patients who fail standard therapies. These therapies can be achieved with chimeric antigen receptor T-cells (CAR-T) and bispecific T-cell engager (TCE) antibodies. We review the most recent advances of CAR T-cells and TCE in the treatment of B-cell lymphomas These advances in immunotherapies have transformed DLBCL prognosis and process indolent NHLs in the future. Results with such therapies may lead to a new standard of care for heavily pretreated patients
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