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    Efficacy and prognostic factors of anti-PD1 and nivolumab-ipilimumab therapy in advanced melanoma patients resistant to prior ICI treatment
    (Springer, 2024) Acar, Caner; Yuksel, Haydar Cagatay; Sahin, Gokhan; Acar, Fatma Pinar; Tunbekici, Salih; Celebi, Gulcin; Karaca, Burcak
    Immune checkpoint inhibitors (ICIs) have significantly improved the five-year survival rate for advanced melanoma. However, many patients exhibit resistance to ICI therapy. This study evaluated the efficacy and prognostic factors of anti-PD-1 (Group A) and nivolumab-ipilimumab (Group B) therapy in patients with advanced melanoma who were resistant to prior ICI therapy. We conducted a retrospective analysis of 56 patients with advanced melanoma who had previously shown resistance to ICI therapy. In the Group A (who have previously shown resistance to anti-CTLA-4, n = 28), the objective response rate (ORR) was 42.9%, with a disease control rate (DCR) of 53%. In the Group B (previously shown resistance to anti-PD-1, n = 28), the ORR was 17.9%, and the DCR was 25%. The ORR was lower in two subgroups: patients who showed progression or relapse in the the initial radiological assessment of prior ICI therapy (ORR 10.5%) and patients who had previously received ICI in the adjuvant setting (ORR 8.3%). A Royal Marsden Hospital (RMH) score of 2-3 was a predictor of OS in both groups (Group A: HR 3.789, 95% CI 1.356-10.589, p = 0.011; Group B: HR 4.281, 95% CI 1.490-12.300, p = 0.007) and for PFS in the Group B (HR 3.167, 95% CI 1.062-9.442, p = 0.039). Anti-PD-1 therapy demonstrated efficacy following resistance to anti-CTLA-4, whereas combination ICI therapy showed lower response rates in patients resistant to anti-PD-1. Further studies are needed to confirm the RMH scores and other prognostic markers and to evaluate subgroups with lower efficacy of nivolumab-ipilimumab therapy.
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    Exploring the Frequency and Risk Factors of Hyperprogressive Disease in Patients with Advanced Melanoma Treated with Immune Checkpoint Inhibitors
    (MDPI, 2024) Acar, Caner; Yuksel, Haydar Cagatay; Sahin, Gokhan; Acar, Fatma Pinar; Karaca, Burcak
    Hyperprogressive disease (HPD) is described as the unexpected rapid growth of a tumour accompanied by a decline in performance status. While immune checkpoint inhibitors (ICIs) have improved outcomes in advanced melanoma, HPD remains a significant challenge in a subset of patients. Although HPD has been extensively studied in various solid tumours, research specifically focusing on advanced melanoma remains limited. We analysed 158 advanced melanoma patients, with 66.5% (n = 105) receiving anti-PD-1 and 33.5% (n = 53) receiving nivolumab plus ipilimumab. The median overall survival was 4.9 months for patients with HPD compared to 8.9 months for those with progressive disease without HPD (p = 0.014). Factors associated with HPD included liver metastasis (p = 0.002), three or more metastatic sites (p < 0.001), elevated lactate dehydrogenase levels (p = 0.004), and Eastern cooperative oncology group performance status >= 2 (p = 0.023). Multivariate analysis identified the Royal Marsden Hospital score (HR 3.675, 95% CI: 1.166-11.580, p = 0.026) as an independent risk factor for HPD, with the MDA-ICI score also trending towards significance (HR 4.466, 95% CI: 0.947-21.061, p = 0.059). This study provides valuable insights into the frequency and factors associated with HPD in advanced melanoma patients treated with ICIs, highlighting the relevance of clinical markers and scoring systems in predicting HPD risk.
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    Rare immune-related adverse effect of pembrolizumab: pulmonary hypertension
    (Taylor & Francis Ltd, 2024) Acar, Caner; Sahin, Gokhan; Yuksel, Haydar Cagatay; Karaca, Burcak
    Pembrolizumab is an immune checkpoint inhibitor that acts via PD-1 blockade. Recent studies have shown its effectiveness in treating various solid organ tumours. However, unlike cytotoxic chemotherapeutic agents, pembrolizumab may cause immune-related adverse effects. These immune-related adverse effects are generally mild, although patients who experience grade-three or higher side effects may require hospitalisation. In particular, cardiopulmonary side effects are associated with high mortality rates. We report the case of a 24-year-old female patient with alveolar soft part sarcoma accompanied by rare and difficult-to-treat pulmonary hypertension induced by pembrolizumab.