Adjuvant treatment of melanoma patients with immune-checkpoint inhibition (ICI) and targeted therapy (TT) significantly improved recurrence-free survival. This study investigates the real-world situation of 904 patients from 13 German skin cancer centers with an indication for adjuvant treatment since the approval of adjuvant ICI and TT. From adjusted log-binomial regression models, we estimated relative risks for associations between various influence factors and treatment decisions (adjuvant therapy yes/no, TT vs. ICI in BRAF mutant patients). Of these patients, 76.9% (95% CI 74–80) opted for a systemic adjuvant treatment. The probability of starting an adjuvant treatment was 26% lower in patients >65 years (RR 0.74, 95% CI 68–80). The most common reasons against adjuvant treatment given by patients were age (29.4%, 95% CI 24–38), and fear of adverse events (21.1%, 95% CI 16–28) and impaired quality of life (11.9%, 95% CI 7–16). Of all BRAF-mutated patients who opted for adjuvant treatment, 52.9% (95% CI 47–59) decided for ICI. Treatment decision for TT or ICI was barely associated with age, gender and tumor stage, but with comorbidities and affiliated center. Shortly after their approval, adjuvant treatments have been well accepted by physicians and patients. Age plays a decisive role in the decision for adjuvant treatment, while pre-existing autoimmune disease and regional differences influence the choice between TT or ICI.

Background: Rhabdoid melanoma is a rare variant of malignant melanoma with characteristic cytomorphologic features. Due to the potential loss of conventional melanocytic markers, histopathologic diagnosis is often challenging. We hypothesize that immunostaining for PReferentially expressed Antigen in MElanoma (PRAME) might have the potential to uncover the melanocytic origin of these dedifferentiated tumors. Methods: Four cases of rhabdoid primary melanomas were assessed by immunohistochemistry for expression of PRAME and conventional melanocytic markers. Immunohistochemical expression patterns were analyzed in the rhabdoid primaries and, if available, associated metastases. Results: All four cases of rhabdoid primary melanomas showed a strong nuclear positivity for PRAME, while the expression of conventional melanocytic markers S100, MART-1, SOX-10 and HMB-45 was variable between the analyzed cases. Conclusions: In summary, we report four cases of rhabdoid primary melanoma with high to intermediate expression of PRAME despite the partial and variable loss of other melanocytic markers. Hence, PRAME might facilitate the recognition of this highly aggressive entity to avoid misdiagnosis due to histopathologic pitfalls.

PURPOSE: Adjuvant treatment with immune checkpoint inhibition (PD-1) and targeted therapy (TT) with BRAF + MEK inhibitors significantly improved recurrence-free survival (RFS) of patients with stage III melanoma. We investigated efficacy of adjuvant therapy with PD-1 or TT under real-world conditions. MATERIALS AND METHODS: A total of 589 patients with stage III melanoma who started adjuvant PD-1 or TT between June 2018 and September 2019 from 11 major German Dermatologic Cooperative Oncology Group skin cancer centers were followed for 4 years. End points were RFS, overall survival (OS), and melanoma-specific survival. Survival analyses and adjusted hazard ratios (HRs) were estimated with Kaplan-Meier and Cox proportional hazards model, inverse probability treatment weighting, and propensity score matching. RESULTS: RFS at 48 months was 42.9% (95% CI, 38.5 to 47.8) for all PD-1 patients and 52.6% (95% CI, 43.6 to 63.3) for TT patients. Among patients with BRAF mutation, rate of recurrence was higher for PD-1 compared with TT (HR, 1.57 [95% CI, 1.09 to 2.26]). OS at 4 years was 80.8% (95% CI, 73.6 to 88.7) for PD-1–treated patients with BRAF mutation and 87.3% (95% CI, 81.0 to 94.0) for TT patients. Patients starting adjuvant PD-1 after resection of macroscopic lymph node metastases had a higher risk of rapid recurrence (1-year RFS all PD-1 58%) compared with 87% in TT patients. Rate of recurrence after premature discontinuation (≤6 v >6 months treatment) was higher in TT patients (HR, 1.47 [95% CI, 0.67 to 3.23]), but not in PD-1 patients (HR, 1.07 [95% CI, 0.73 to 1.55]). CONCLUSION: PD-1–treated patients with BRAF mutation had a markedly higher rate of relapse compared with TT patients. Rapid recurrences occurred particularly in PD-1–treated patients with previous macroscopic lymph node metastasis. Treatment duration shorter than 6 months did not negatively affect RFS in PD-1, but in TT patients.

Background: Merkel cell carcinoma (MCC) is a rare but highly aggressive cutaneous malignancy. Immune checkpoint inhibition (ICI) with PD-(L)1 blockade has significantly improved treatment outcomes in metastatic disease. In patients with primary resistance to PD-(L)1 inhibition, a high overall response rate (ORR) of 50% to later-line ipilimumab plus nivolumab (IPI/NIVO) has been demonstrated. However, clinical data on patients with progression after an initial response to IPI/NIVO are still lacking.Methods: Clinical data of three metastatic MCC patients who were re-exposed to IPI/NIVO after progression were retrospectively evaluated.Results: Two of the three patients showed primary resistance to avelumab with progressive disease, while one patient showed complete response (according to RECIST V.1.1). All three patients received combined ICI with IPI/NIVO as subsequent therapy, resulting in an ORR of ∼ 67%. However, all three patients progressed during follow-up and were re-exposed to IPI/NIVO. With a follow-up period ranging from 6.5 to 37.1 months, no PFS event has been detected. ORR for IPI/NIVO re-exposition was equal to that of initial IPI/NIVO treatment.Conclusion: In this retrospective follow-up analysis, we observed a response rate of 67% and long-lasting responses after re-exposition to combined ICI in metastatic MCC patients with progression after initial response or disease control upon their first IPI/NIVO treatment. An important observation from this small analysis is that primary resistance to PD-L1 inhibition may result in a better response to IPI/NIVO.