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This is the largest series of patients with pre-existing AD and treatment with ipilimumab reported. Flares of pre-existing AD were observed but manageable. Response rates and occurrence of new irAEs were comparable to previous trials. Thus, in this patient subgroup, ipilimumab can be a treatment option after a thorough discussion of pros and cons and taking severity and activity of the preexisting AD into account.

PURPOSE BRAF/MEK inhibition is a standard of care for patients with BRAF V600E/K–mutated metastatic melanoma. For patients with less frequent BRAF mutations, however, efficacy data are limited. METHODS In the current study, 103 patients with metastatic melanoma with rare, activating non-V600E/K BRAF mutations that were treated with either a BRAF inhibitor (BRAFi), MEK inhibitor (MEKi), or the combination were included. BRAF mutation, patient and disease characteristics, response, and survival data were analyzed. RESULTS Fifty-eight patient tumors (56%) harbored a non-E/K V600 mutation, 38 (37%) a non-V600 mutation, and seven had both V600E and a rare BRAF mutation (7%). The most frequent mutations were V600R (43%; 44 of 103), L597P/Q/R/S (15%; 15 of 103), and K601E (11%; 11 of 103). Most patients had stage IV disease and 42% had elevated lactate dehydrogenase at BRAFi/MEKi initiation. Most patients received combined BRAFi/MEKi (58%) or BRAFi monotherapy (37%). Of the 58 patients with V600 mutations, overall response rate to BRAFi monotherapy and combination BRAFi/MEKi was 27% (six of 22) and 56% (20 of 36), respectively, whereas median progression-free survival (PFS) was 3.7 months and 8.0 months, respectively ( P = .002). Of the 38 patients with non-V600 mutations, overall response rate was 0% (zero of 15) to BRAFi, 40% (two of five) to MEKi, and 28% (five of 18) to combination treatment, with a median PFS of 1.8 months versus 3.7 months versus 3.3 months, respectively. Multivariable analyses revealed superior survival (PFS and overall survival) with combination over monotherapy in rare V600 and non-V600 mutated melanoma. CONCLUSION Patients with rare BRAF mutations can respond to targeted therapy, however, efficacy seems to be lower compared with V600E mutated melanoma. Combination BRAFi/MEKi seems to be the best regimen for both V600 and non-V600 mutations. Yet interpretation should be done with care because of the heterogeneity of patients with small sample sizes for some of the reported mutations.

Cutaneous metastases of internal malignancies still seem to occur infrequently, although medical publications report an incidence rate of up to 10.4%. Common sense, however, fosters suspicion that we might underdiagnose the problem distracted by harder striking facets of an advanced disease. With contemporary knowledge, morphology and behavior of cutaneous metastases resemble each other regardless of the site of origin. This article itemizes clinical presentations according to organ systems, specific features, and differential diagnoses. In general, the survival turned out to be less than 12 months. But incremental awareness of cutaneous metastases proclaims this paradigm insufficient. Although excision is the local treatment of choice, investigations attempt to propose tumor-specific chemotherapeutic/immunological approaches. This paper endeavors to critically review the state of the art concerning the clinic, prognosis, and therapeutic concepts.

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StatementDie Behandlungsstrategien basieren auf der exakten Diagnose, den Vorbehandlungen und auf dem Erkrankungsstadium.Konsensus: 100 % EmpfehlungenDie Therapie der MF soll entsprechend den in Tabelle 1 gelisteten Empfehlungen erfolgen. Konsensus: 100 % Die Therapie des Sézary-Syndroms soll entsprechend den in Tabelle 2 gelisteten Empfehlungen erfolgen. Konsensus: 86 % Die Therapie der CD30+ lymphoproliferativen Erkrankungen der Haut soll entsprechend den in Tabelle 3 gelisteten Empfehlungen erfolgen. Konsensus: 100 % Die Therapie der kutanen B Zell-Lymphome soll entsprechend den Tabellen 4a und 4b gelisteten Empfehlungen erfolgen. Konsensus: 100 %

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