Lacher Fellowship established by The Lymphoma Foundation (MJ Pianko), and is also supported in part by a grant from the National Institutes of Health/National Center for Advancing Translational Sciences (UL1TR00457), administered by the Clinical and Translational Science Center at Weill Cornell Medical Center and MSKCC. of PD-1/PD-L1 blockade in NHL Pirozadil has been limited to phase I studies inclusive of multiple types of HM and Pirozadil some phase II studies demonstrating activity in DLBCL and FL (priming of T cells by DC that have processed tumor cell antigen outside the confines of the local MM TME (78). Pirozadil In preclinical studies, syngeneic mice lacking PD-1 completely suppress growth of a MM tumor cell line (J558L), whereas mice expressing PD-1 rapidly develop tumor (79), suggesting a potential role for PD-1 blockade in treatment of myeloma. In the 5T33 model of myeloma, use of an anti-PD-L1 antibody in combination with lymphodepletion with radiation and a vaccine led to anti-myeloma activity (80). This effect was abrogated by depletion of CD4 or CD8 T cells, indicating that presence and function of both T cell subsets are necessary for this effect (80,81). Although preclinical data supports a rationale for PD-1 blockade, nivolumab monotherapy did not show clinical efficacy (44) (nivolumab plus daratumumab, pomalidomide, and dexamethasone in R/R MM. Nivolumab, elotuzumab, pomalidomide, and dexamethasone will be evaluated Pirozadil in CheckMate 602 (“type”:”clinical-trial”,”attrs”:”text”:”NCT02726581″,”term_id”:”NCT02726581″NCT02726581). There are also trials underway in smoldering MM (pembrolizumab, “type”:”clinical-trial”,”attrs”:”text”:”NCT02603887″,”term_id”:”NCT02603887″NCT02603887; nivolumab plus lenalidomide and dexamethasone, “type”:”clinical-trial”,”attrs”:”text”:”NCT02903381″,”term_id”:”NCT02903381″NCT02903381). Studies are enrolling patients for treatment with ipilimumab plus nivolumab after ASCT (“type”:”clinical-trial”,”attrs”:”text”:”NCT02681302″,”term_id”:”NCT02681302″NCT02681302) and after allo-HSCT (“type”:”clinical-trial”,”attrs”:”text”:”NCT 01822509″,”term_id”:”NCT01822509″NCT 01822509). A study evaluating durvalumab (anti-PD-L1) plus tremelimumab (anti-CTLA-4) after ASCT is also underway (“type”:”clinical-trial”,”attrs”:”text”:”NCT02716805″,”term_id”:”NCT02716805″NCT02716805). Table 5 Select open and upcoming immune checkpoint trials in MM Rabbit Polyclonal to OR5AS1 and plasma cell disorders This work was supported in part by the Memorial Sloan Kettering Cancer Center (MSKCC) NCI core grant P30 CA008748 (AM Lesokhin), Pirozadil the Mortimer J. Lacher Fellowship established by The Lymphoma Foundation (MJ Pianko), and is also supported in part by a grant from the National Institutes of Health/National Center for Advancing Translational Sciences (UL1TR00457), administered by the Clinical and Translational Science Center at Weill Cornell Medical Center and MSKCC. AM Lesokhin is usually a member of the Parker Institute for Cancer Immunotherapy, which supported the MSKCC Cancer Immunotherapy Program. AM Lesokhin also receives support from the Memorial Sloan Kettering Sawiris Foundation and MSKCC Cycle for Survival. Footnotes AM Lesokhin: Stock or other ownership: Exelixis, Enumeral; Honoraria: Bristol-Myers Squibb, Janssen Pharmaceuticals (a Johnson & Johnson Co.), Gilead Sciences (I), Novartis; Consulting or advisory role: Bristol-Myers Squibb, Foundation Medicine (Inst), Janssen Pharmaceuticals (a Johnson & Johnson Co.), Novartis, Juno, Aduro; Research funding: Bristol-Myers Squibb (Inst), Janssen Pharmaceuticals (a Johnson & Johnson Co.) (Inst); Patents, royalties, other intellectual property: Serametrix. The other authors have no conflicts of interest to declare..
