Main
non-small cell lung cancer, death, tumor, Tislelizumab, leukemia, CLL, B cell non-Hodgkin lymphoma
NON-SMALL CELL LUNG CANCER, CLL, TUMOR, REMISSIONS, ADVERSE EVENTS, LEUKEMIA, MALIGNANCIES, CHRONIC LYMPHOCYTIC LEUKEMIA
Chronic lymphocytic leukemia (CLL) is classified as an indolent B cell non-Hodgkin lymphoma according to the World Health Organization classification and is the most common type of leukemia in adultsProgrammed cell death protein 1 (PD-1) is an important immune-checkpoint receptor that is predominantly expressed on activated T cells and transmits inhibitory signals into T cells after ligation with PD-L1 or PD-L2 on malignant cells and the tumor microenvironmentThough checkpoint inhibitors are promising candidates for treatment of RT, single-agent treatment with PD-1 inhibitors did not prevent progression of CLLBTK inhibitors have become a cornerstone of CLL therapy, as B cell receptor (BCR) signaling is a key dependency of CLL cells that is required to sustain prosurvival signals from the microenvironmentBased on preclinical and translational data that suggested immune-checkpoint inhibition and BTK inhibition as possible vulnerabilities of RT, we hypothesized that a combination of tislelizumab and zanubrutinib could be an effective strategy to induce remissions in patients with RT, who are treatment-naive or have received up to one previous line of RT-directed therapy. Tislelizumab is a humanized, immunoglobulin G4-variant monoclonal antibody against PD-1 that has been explored in solid malignancies and has demonstrated low rates of immune-related adverse events and good efficacy. Tislelizumab has previously demonstrated efficacy in a variety of solid malignancies, including in the first-line treatment of advanced non-small cell lung cancer and esophageal cancerHere, we present data of the international, investigator-initiated phase 2 RT1 trial, in which the PD-1 inhibitor tislelizumab was combined with the next-generation BTK inhibitor zanubrutinib to treat patients with RT, with the objective to compare the ORR after six cycles with the prespecified benchmark of 40%.