Efficacy of immunotherapy for melanoma brain metastases in patients with concurrent corticosteroid exposure.

Aim: Immune checkpoint inhibitor (ICI) efficacy is undefined for melanoma brain metastases (MBM) with concurrent corticosteroid exposure. Materials & methods: We retrospectively evaluated patients with untreated MBM who received corticosteroids (≥1.5 mg dexamethasone equivalent) within 30 days of ICI. mRECIST criteria and Kaplan-Meier methods defined intracranial progression-free survival (iPFS). The lesion size-response association was evaluated with repeated measures modeling. Results: A total of 109 MBM were evaluated. The patient level intracranial response rate was 41%. Median iPFS was 2.3 months and overall survival was 13.4 months. Larger lesions were more likely to progress, with diameter >2.05 cm most predictive of progression (OR: 18.9; 95% CI: 2.6-139.5; p = 0.004). There was no difference in iPFS with steroid exposure pre- versus post-ICI initiation. Conclusion: In the largest reported ICI+corticosteroid cohort, we identify size dependent MBM response.

Checkpoint inhibitor immunotherapy stimulates the body to attack melanoma and other cancers, but the immune system can be counteracted by steroid medication. On the other hand, steroids are sometimes needed to reduce swelling caused by brain tumors. To understand whether steroid use at the same time as immunotherapy impacts the response in melanoma brain metastases, the authors examined how 17 such patients fared. Brain tumors in these patients responded fairly well, though this was especially the case in the smaller tumors. This may help guide how patients with melanoma brain metastases are treated in the future.

Case report: Later onset of NRAS-mutant metastatic melanoma in a patient with a partially-excised giant congenital melanocytic nevus.

Despite recent advances in treatment and surveillance, metastatic melanoma still carries a poor prognosis. Large/giant congenital melanocytic nevi (CMNs) constitute a known risk factor for the condition, with the greatest risk for malignant transformation thought to be during childhood (median age at diagnosis of 3 years in a previous cohort). Herein, we present the case of a 30-year-old male who, after undergoing multiple excision/grafting procedures for a giant CMN as a child, was diagnosed with an NRAS-mutant, MDM2-amplified metastatic melanoma more than 20 years later. Response to ipilimumab/nivolumab immunotherapy, cisplatin/vinblastine/temozolomide chemotherapy, and nivolumab/relatlimab immunotherapy was poor. This case highlights the importance of lifetime monitoring with once-yearly dermatological examination (including lymph node palpation) in large/giant CMN patients, as well as the need for further clinical trials evaluating novel therapies for NRAS-mutant melanoma.