Non-Hodgkin lymphomas (NHLs) are lymphoid malignancies of B- or T-cell origin. Despite great advances in treatment options and significant improvement of survival parameters, a large part of NHL patients either present with a chemotherapy-refractory disease or experience lymphoma relapse. Chemotherapy-based salvage therapy of relapsed/refractory NHL is, however, capable of re-inducing long-term remissions only in a minority of patients. Immunotherapy-based approaches, including bispecific antibodies, immune checkpoint inhibitors and genetically engineered T-cells carrying chimeric antigen receptors, single-agent or in combination with therapeutic monoclonal antibodies, immunomodulatory agents, chemotherapy or targeted agents demonstrated unprecedented clinical activity in heavily-pretreated patients with NHL, including chemotherapy-refractory cases with complex karyotype changes and other adverse prognostic factors. In this review, we recapitulate currently used immunotherapy modalities in NHL and discuss future perspectives of combinatorial immunotherapy strategies, including patient-tailored approaches.

1st Department of Internal Medicine Hematology University General Hospital Prague and 1st Faculty of Medicine Charles University U Nemocnice 2 128 08 Prague 2 110 00 Prague Czech Republic

Institute of Haematology and Blood Transfusion 128 00 Prague Czech Republic

Institute of Pathological Physiology 1st Faculty of Medicine Charles University 128 53 Prague Czech Republic

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Chimeric Antigen Receptor Based Cellular Therapy for Treatment Of T-Cell Malignancies