The New England Journal of MedicineCase 2-2024: A 57-Year-Old Woman with Melanoma and Fever

BRAF–MEK Inhibitor-Related Toxic Effects: Unveiling the Challenges in Managing Advanced Melanoma Treatment Complications

This article presents a comprehensive case study of a 57-year-old woman with stage IIIC cutaneous melanoma, highlighting the complexities and challenges encountered during her treatment with BRAF–MEK inhibitors. The patient’s journey, from initial diagnosis through various treatment phases, sheds light on the critical aspects of managing advanced melanoma, particularly focusing on the toxic effects associated with targeted therapy. The detailed analysis offers valuable insights for physicians in understanding the nuances of treatment-induced complications, contributing to informed decision-making in similar clinical scenarios.

Key Points:

1. Initial Presentation: A 57-year-old woman with a history of stage IIIC cutaneous melanoma presented with fever, four months post-diagnosis, following bleeding from a scalp lesion.
2. Diagnosis and Treatment Plan: Melanoma was diagnosed after a scalp lesion biopsy; she underwent wide local excision and neck lymph-node dissection, revealing metastatic melanoma in lymph nodes.
3. Targeted Therapy Initiation: Post-surgery, the patient began treatment with dabrafenib (a BRAF inhibitor) and trametinib (a MEK inhibitor) following the identification of the BRAF V600E mutation.
4. Adverse Reactions: The patient developed fever and nausea one day after starting targeted therapy, leading to temporary discontinuation and treatment with acetaminophen and ibuprofen.
5. Recurrent Fever Episodes: Fever recurred multiple times post-reinitiation of dabrafenib and trametinib, with normal liver and kidney function tests.
6. Hospital Admission: Persistent fever and additional symptoms like fatigue, light-headedness, and right upper quadrant pain led to hospital admission.
7. Investigative Findings: Laboratory tests showed acute kidney injury, liver injury, and abnormalities in white-cell count and platelet count; imaging studies indicated possible hepatic steatosis and pulmonary issues.
8. Differential Diagnosis: The patient’s complex presentation led to a challenging differential diagnosis process, considering both infectious and noninfectious causes.
9. Final Diagnosis: BRAF–MEK inhibitor-related toxic effects were confirmed by liver biopsy, showing nonnecrotizing epithelioid granulomas and patchy mixed inflammation.
10. Treatment and Outcome: Post-diagnosis, symptoms resolved and liver enzyme levels decreased upon discontinuation of dabrafenib and trametinib. The patient eventually chose to cease targeted therapy in favor of immunotherapy, leading to a later diagnosis of metastatic melanoma recurrence and subsequent decline in health, culminating in her passing.

Did you know that BRAF mutations are found in approximately 50% of melanomas? This mutation’s prevalence underscores the importance of understanding the implications of targeted therapies in melanoma management.

More on Melanoma