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The relationship between immune related adverse events (irAEs) and efficacy is not definitively proven, and data on the relationship between irAE and treatment efficacy are contradictory. Five hundred ninety-three consecutive patients with unresectable or metastatic melanoma treated in the first line with anti-PD-1 (nivolumab or pembrolizumab) between January 2016 and December 2019 were enrolled in the study. Statistically significant differences were demonstrated between the group of patients without and with irAE in median OS and PFS (p < .0001 both) and also in OS between the group of patients without irAE and patients with irAE within 3, 6, and 9 months from the start of anti-PD-1 therapy (p = .0121, p = .0014, p < .0001; respectively) and PFS (p = .0369, p = .0052, p = .0001; respectively). A statistically significant relationship was demonstrated between the occurrence of irAE and the location of the primary tumor (skin vs. mucosa vs. unknown; p = .0183), brain metastasis (present vs. absent; p = .0032), other locations (present vs. absent, p = .0032), LDH (normal vs. elevated; p = .0046) and stage according to TNM (p = .0093). The occurrence of irAE was associated with longer OS, PFS, and more frequent response to treatment. IrAE occurred statistically significantly more often in patients with mucosa primary tumor, with normal LDH levels, without brain metastases, stages III, M1a, and M1b.

e21539 Background: The use of targeted therapies (TT) and checkpoint inhibitors (IT) significantly prolonged survival in patients with metastatic melanoma, especially in patients with BRAF mutation-positive melanoma. Optimal sequence of therapies use is still a matter of debate. The aim of this study was to evaluate real-life practice and outcomes in melanoma patients treated sequentially. Methods: Consecutive patients with BRAF mutation-positive unresectable or metastatic melanoma started treatment with TT (BRAF and MEK inhibitors) and/or IT (anti-PD1) between 1/Oct/2016 and 31/Dec/2020. Clinical factors including age, gender, ECOG performance status, baseline LDH level, and location of metastases, response to treatment and irAEs occurrence were analyzed. Survival analyses were performed using the Kaplan-Meier method, Log-rank and chi-square tests were used for comparison between groups. Data cut-off was 31/Dec/2021. Results: In total 585 patients were enrolled. 170 (29%) patients were treated with IT and 415 (71%) with TT in the first line. 331 patients (56%) received only one line of treatment – 247/415 (59%) patients only TT and 84/170 (49%) patients received only IT (anti-PD1). Disease progression was found in 175 (71%) patients in the only TT group and in 43 (51%) in the only IT group. 254 patients qualified for sequential treatment 168 (29%) patients received TT then IT (TT-IT), 64 (11%) IT then TT (IT-TT), and 22 (4%) IT-IT (anti-PD-1 then anti-CTLA-4). Patients with brain metastases and elevated LDH were statistically more often treated with first line TT and more patients with normal LDH level received IT-IT therapy. No other statistically significant differences in baseline characteristics was found for IT-TT, TT-IT and IT-IT groups. The estimated median OS (mOS) was not reached in patients treated with only one line of IT treatment, while for TT only it was only 11.8 months. Estimated mOS for patients treated in the first line with IT or TT was significantly different (p = 0.02; HR = 0.74, Cl 95% 0.6-0.9) and reached 25.6 and 15.3 months, respectively; although no statistically significant mOS differences was found in the subgroups without brain metastases (p = 0.56) and with normal LDH (p = 0.36). For sequential treatment groups mOS for IT-TT, TT-IT, and IT-IT was 19.6, 19.9 and 35.9 months, respectively. There was no statistically significant difference in OS between IT-TT and TT-IT treated groups (p = 0.56), and between IT-TT, TT-IT and IT-IT groups (p = 0.19). Conclusions: Patients who were treated with IT in the 1st line had better OS than patients treated TT in the 1st line in real-world data but this may be related to better prognostic factors in the IT group. Selected patients receiving IT in the first line achieve long OS, which is a result of a long-term response to IT. Novel predictive biomarkers factors of IT response should be incorporated in prospective trials.

(1) Background: BRAFi/MEKi are usually offered as a first line treatment for patients requiring rapid response; with elevated lactate dehydrogenase (LDH) activity, large tumor burden, and with brain metastases. The efficacy of second line therapies after BRAFi/MEKI failure is now well defined. (2) Methods: Patients treated with first line target BRAFi/MEKi therapy (vemurafenib plus cobimetinib, dabrafenib plus trametinib or encorafenib plus binimetinib); and for the second line treatment immunotherapy with programmed cell death 1 (PD-1) checkpoint inhibitors (nivolumab or pembrolizumab) with at least one cycle of second line were analyzed for survival and prognostic biomarkers. (3) Results: There were no statistically significant differences in ORR between the treatment groups with nivolumab and pembrolizumab, as well as median progression free-survival (PSF) and overall survival (OS) since the initiation of second line therapy; on nivolumab OS was 6.6 months, and on pembrolizumab 5.0 months. The greatest clinical benefit with second line immunotherapy was observed in patients with LDH ≤ ULN and 6 months in first line (slow progression). (4) Conclusions: Second line anti-PD1 immunotherapy is effective in BRAF-mutated melanoma patients after BRAFi/MEKi therapy failure.

e21514 Background: Anti-programmed cell death-1 antibodies (anti-PD-1) have become a standard treatment option for melanoma patients. Currently, two anti-PD-1 antibodies are registered in the treatment of melanoma patients: nivolumab and pembrolizumab. Nivolumab is a human monoclonal antibody, while pembrolizumab is a humanized antibody. Unfortunately, there are very few clinical data comparing the efficacy and toxicity of nivolumab and pembrolizumab in routine practice. Methods: Consecutive patients treated in the first line with anti-PD-1 (nivolumab or pembrolizumab) for unresectable or metastatic melanoma in comprehensive cancer centers between 03/2016 and 09/2020 were enrolled in the analysis. Baseline factors (age, gender, primary location of melanoma, BRAF mutation status, ECOG performance status, baseline LDH level, and location of metastases) were evaluated to identify predictors of overall survival (OS). Data on response to treatment and the occurrence of irAEs were collected prospectively during anti-PD-1 treatment. OS were assessed using Kaplan–Meier and Cox models. The Chi-Square statistic was used for testing relationships between categorical variables. Median follow up for nivolumab and pembrolizumab group was 12.6 (range 0.2-52.1) and 10.7 (range 0.03-53.5) months, respectively. Results: Overall, 736 patients were included in the present analysis (443 nivolumab, 293 pembrolizumab). There were no statistically significant differences in baseline factors (age, gender, primary location of melanoma, BRAF mutation status, ECOG performance status, baseline LDH level (normal vs elevated), brain metastasis and TNM stage) between the groups. Median OS for patients treated with nivolumab and pembrolizumab was 22 and was 17.3 months, respectively. There was no statistically significant difference in OS between the nivolumab and pembrolizumab groups (p = 0.12, HR = 1.2, Cl 95% 0.9-1.4). At multivariate analysis normal LDH levels, no brain metastases, and ECOG 0 or 1 were positive prognostic factors for OS both in nivolumab and pembrolizumab groups. In the nivolumab and pembrolizumab groups, 6% and 5% CR (complete response), 33% and 31% PR (partial response), 25% and 24% SD (stable disease), respectively, were observed. There was no statistical difference between the groups in the response to treatment (p = 0.65). There was no statistical difference between the groups in occurrence of the irAEs (p = 0.97) as well as in the type of irAEs. Conclusions: Our analysis in melanoma patients treated in routine practice with nivolumab or pembrolizumab confirmed no statistical differences in OS and treatment responses between these two anti-PD-1 antibodies. There were also no differences in toxicity between the two drugs. The choice of treatment should be based on the preferences of the patient and the physician.

Laryngeal cancer occurs rarely in adolescents and young people. Castleman’s disease is a rare lymphoproliferative disorder of uncertain etiopathogenesis and heterogeneous clinicopathological forms. Involved lymph nodes and extranodal lesions in the course of Castleman’s disease may mimic malignant involvement. We report a case of an 18-year-old woman with T2N0M0 laryngeal glottis cancer treated with definitive radiotherapy. During the irradiation, the patient underwent an excision of incidentally discovered left-sided enlarged cervical lymph nodes located outside the irradiated area. Coincidental hyaline vascular type of Castleman’s disease was diagnosed. During six-year follow-up she has been free of cancer relapse and Castleman’s disease symptoms.