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Objective: The efficacy of combined BRAF and MEK inhibition for BRAF V600-mutant melanoma in a broad patient population, including subgroups excluded from phase 3 trials, remains unanswered. This noninterventional study (DATUM-NIS) assessed the real-world efficacy, safety and tolerability of dabrafenib plus trametinib in Austrian patients with unresectable/metastatic melanoma., Methods: This multicenter, open-label, non-interventional, post-approval, observational study investigated the effectiveness of dabrafenib plus trametinib prescribed in day-to-day clinical practice to patients ( N  = 79) with BRAF V600-mutant unresectable/metastatic melanoma with M1c disease (American Joint Committee on Cancer staging manual version 7), ECOG > 1, and elevated serum lactate dehydrogenase (LDH). The primary endpoint was 6-, 12- and 18-month progression-free survival (PFS) rates. Secondary endpoints were median PFS, disease control rate and overall survival (OS)., Results: The 6-, 12- and 18-month PFS rates were 76%, 30.6% and 16.2%, respectively. Subgroup analysis showed a significant PFS benefit in the absence of lung metastasis. The median PFS and OS were 9.1 (95% CI, 7.1-10.3) months and 17.9 (95% CI, 12.7-27.8) months, respectively. The 12- and 24-month OS rates were 62.7% and 26.8%, respectively. Subgroup analyses showed significant OS benefits in the absence of bone or lung metastasis and the presence of other metastases (excluding bone, lung, brain, liver and lymph nodes). Furthermore, S100 and Eastern Cooperative Oncology Group performance status (ECOG PS) showed a significant impact on survival. No new safety signals were observed., Conclusion: Despite an unselected population of melanoma patients with higher M1c disease, ECOG PS > 1 and elevated LDH, this real-world study demonstrated comparable efficacy and safety with the pivotal phase 3 clinical trials for dabrafenib-trametinib., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

In this case report, we describe a patient with an inoperable mucosal melanoma of the sinonasal cavity who achieved an ongoing complete response to combined immunotherapy with ipilimumab and nivolumab after initial pseudoprogression. Despite massive enlargement of the tumor 9 weeks after treatment initiation, we decided to continue with checkpoint inhibitor immunotherapy because of lacking potent therapeutic alternatives and the possibility of pseudoprogression. In the computed tomography scan 3 months later, the tumor was no longer detectable. To date, the patient is still in remission. However, she developed severe immune-related thrombocytopenia and neutropenia that are rarely encountered with checkpoint inhibitor immunotherapy. Thrombocytopenia did not respond to corticosteroids, but rapidly improved after the administration of single-dose intravenous immunoglobulin. This exceptional case highlights the effectiveness of combined immunotherapy with ipilimumab and nivolumab in mucosal melanoma, the phenomenon of pseudoprogression, as well as the rare event of immune-related hematological side effects.