Response to Ipilimumab/Nivolumab Rechallenge and BRAFInhibitor/MEK Inhibitor Rechallenge in a Patient with AdvancedMetastatic Melanoma Previously Treated with BRAF TargetedTherapy and Immunotherapy

Little is known about the optimal sequencing of targeted therapy and immunotherapy in the treatment of patients with BRAFV600-mutated metastatic melanoma. BRAF/MEK inhibition often has the benefit of rapid disease regression; however, resistance isfrequently seen with long-term use. Treatment with immune checkpoint inhibitors offers the potential for long-term responsebut displays a lower rate of objective response. The benefit of synergy between therapies is apparent; however, there is limiteddata regarding optimal sequencing in the treatment of advanced melanoma. We present the case of a 62-year-old gentlemanwith advanced BRAFV600-mutated melanoma who followed an unconventional treatment path. After progressing on single-agent vemurafenib, he had response to multiple modalities of immunotherapy before progression. After, he had a substantialresponse to multiple BRAF/MEK inhibitor rechallenges before developing resistance. The patient is now stable after a retrial ofcombination immunotherapy. Our case illustrates that with the right sequencing of therapy, meaningful clinical responses canbe elicited with rechallenging of targeted therapy and immunotherapy in metastatic melanoma.