Journal for immunotherapy of cancer · 2019
Efficacy and tolerability of anti-programmed death-ligand 1 (PD-L1) antibody (Avelumab) treatment in advanced thymoma.
СтатьяПоддержка NIH: внешняя программаResearch Support, N.I.H., IntramuralПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Rajan Arun, Heery Christopher R, Thomas Anish, Mammen Andrew L, Perry Susan, O'Sullivan Coyne Geraldine, Guha Udayan, Berman Arlene, Szabo Eva, Madan Ravi A, Ballester Leomar Y, Pittaluga Stefania, Donahue Renee N, Tsai Yo-Ting, Lepone Lauren M, Chin Kevin, Ginty Fiona, Sood Anup, Hewitt Stephen M, Schlom Jeffrey, Hassan Raffit, Gulley James L
Аннотация
BACKGROUND: Thymic epithelial tumors are PD-L1-expressing tumors of thymic epithelial origin characterized by varying degrees of lymphocytic infiltration and a predisposition towards development of paraneoplastic autoimmunity. PD-1-targeting antibodies have been evaluated, largely in patients with thymic carcinoma. We sought to evaluate the efficacy and safety of the anti-PD-L1 antibody, avelumab (MSB0010718C), in patients with relapsed, advanced thymic epithelial tumors and conduct correlative immunological studies.
METHODS: Seven patients with thymoma and one patient with thymic carcinoma were enrolled in a phase I, dose-escalation trial of avelumab (MSB0010718C), and treated with avelumab at doses of 10 mg/kg to 20 mg/kg every 2 weeks until disease progression or development of intolerable side effects. Tissue and blood immunological analyses were conducted.
RESULTS: Two of seven (29%) patients with thymoma had a confirmed Response Evaluation Criteria in Solid Tumors-defined partial response, two (29%) had an unconfirmed partial response and three patients (two thymoma; one thymic carcinoma) had stable disease (43%). Three of four responses were observed after a single dose of avelumab. All responders developed immune-related adverse events that resolved with immunosuppressive therapy. Only one of four patients without a clinical response developed immune-related adverse events. Responders had a higher absolute lymphocyte count, lower frequencies of B cells, regulatory T cells, conventional dendritic cells, and natural killer cells prior to therapy.
CONCLUSION: These results demonstrate anti-tumor activity of PD-L1 inhibition in patients with relapsed thymoma accompanied by a high frequency of immune-related adverse events. Pre-treatment immune cell subset populations differ between responders and non-responders.
TRIAL REGISTRATION: ClinicalTrials.gov - NCT01772004 . Date of registration - January 21, 2013.
METHODS: Seven patients with thymoma and one patient with thymic carcinoma were enrolled in a phase I, dose-escalation trial of avelumab (MSB0010718C), and treated with avelumab at doses of 10 mg/kg to 20 mg/kg every 2 weeks until disease progression or development of intolerable side effects. Tissue and blood immunological analyses were conducted.
RESULTS: Two of seven (29%) patients with thymoma had a confirmed Response Evaluation Criteria in Solid Tumors-defined partial response, two (29%) had an unconfirmed partial response and three patients (two thymoma; one thymic carcinoma) had stable disease (43%). Three of four responses were observed after a single dose of avelumab. All responders developed immune-related adverse events that resolved with immunosuppressive therapy. Only one of four patients without a clinical response developed immune-related adverse events. Responders had a higher absolute lymphocyte count, lower frequencies of B cells, regulatory T cells, conventional dendritic cells, and natural killer cells prior to therapy.
CONCLUSION: These results demonstrate anti-tumor activity of PD-L1 inhibition in patients with relapsed thymoma accompanied by a high frequency of immune-related adverse events. Pre-treatment immune cell subset populations differ between responders and non-responders.
TRIAL REGISTRATION: ClinicalTrials.gov - NCT01772004 . Date of registration - January 21, 2013.
Предметные рубрики MeSH
AdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalB7-H1 AntigenBiomarkersBiomarkers, TumorFemaleGene Expression ProfilingHumansImmunohistochemistryImmunophenotypingMaleMiddle AgedMolecular Targeted TherapyNeoplasm StagingThymomaThymus NeoplasmsTomography, X-Ray ComputedTreatment Outcome