Immune checkpoint blockers in solid organ transplant recipients and cancer: the INNOVATED cohort

实体器官移植受者和癌症患者的免疫检查点阻断剂:INNOVATED队列研究

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Abstract

BACKGROUND: Patients with solid organ transplant (SOT) and solid tumors are usually excluded from clinical trials testing immune checkpoint blockers (ICB). As transplant rates are increasing, we aimed to evaluate ICB outcomes in this population, with a special focus on lung cancer. METHODS: We conducted a multicenter retrospective cohort study collecting real data of ICB use in patients with SOT and solid tumors. Clinical data and treatment outcomes were assessed by using retrospective medical chart reviews in every participating center. Study endpoints were: overall response rate (ORR), 6-month progression-free survival (PFS), and grade ≥3 immune-related adverse events. RESULTS: From August 2016 to October 2022, 31 patients with SOT (98% kidney) and solid tumors were identified (36.0% lung cancer, 19.4% melanoma, 13.0% genitourinary cancer, 6.5% gastrointestinal cancer). Programmed death-ligand 1 expression was positive in 29% of tumors. Median age was 61 years, 69% were males, and 71% received ICB as first-line treatment. In the whole cohort the ORR was 45.2%, with a 6-month PFS of 56.8%. In the lung cancer cohort, the ORR was 45.5%, with a 6-month PFS of 32.7%, and median overall survival of 4.6 months. The grade 3 immune-related adverse events rate leading to ICB discontinuation was 12.9%. Allograft rejection rate was 25.8%, and risk of rejection was similar regardless of the type of ICB strategy (monotherapy or combination, 28% versus 33%, P = 1.0) or response to ICB treatment. CONCLUSIONS: ICB could be considered a feasible option for SOT recipients with some advanced solid malignancies and no alternative therapeutic options. Due to the risk of allograft rejection, multidisciplinary teams should be involved before ICB therapy.

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