Successful treatment of BRAF/MEK inhibitor-resistant advanced cutaneous melanoma with nivolumab plus ipilimumab combination therapy followed by intensity-modulated radiotherapy

BRAF kinase inhibitors in combination with MEK kinase inhibitors are among the most promising chemotherapeutic regimens for the treatment of advanced BRAF-mutant melanoma. Although the NCCN guideline for cutaneous melanoma recommended BRAF/MEK inhibitors as first-line therapies for unresectable BRAF-mutated melanoma, resistance to these drugs should be taken into account in real-world practice. Therefore, development of a protocol for BRAF/MEK inhibitor-resistant advanced melanoma is needed. In this report, a case of BRAF/MEK inhibitor-resistant advanced cutaneous melanoma that was successfully treated with nivolumab plus ipilimumab combination therapy followed by intensity-modulated radiotherapy (IMRT) is reported. In the present case, not only the locally irradiated lesion, but remote metastases including inguinal lymph nodes decreased after ipilimumab plus nivolumab followed by IMRT treatment leading to complete remission, suggesting that IMRT triggered an abscopal response. Moreover, immunohistochemical analysis showed increased CD3⁺, CD4⁺, and CD8⁺ T cells after radio-immunotherapy (RIT). This case suggests that RIT might break the tolerance in the tumor microenvironment and induce a systemic anti-melanoma immune response.