Case Report: triple therapy with pembrolizumab, ipilimumab, and lenvatinib in mitotane- and radiation-refractory, cortisol-secreting stage IV adrenocortical carcinoma: a genomically guided approach - Report - MDSpire
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Case Report: triple therapy with pembrolizumab, ipilimumab, and lenvatinib in mitotane- and radiation-refractory, cortisol-secreting stage IV adrenocortical carcinoma: a genomically guided approach
Clinical Report: Combination Therapy for Stage IV Adrenocortical Carcinoma
Overview
This report details a case of a 54-year-old woman with stage IV adrenocortical carcinoma (ACC) resistant to conventional therapies, who achieved a significant clinical response to a combination of pembrolizumab, ipilimumab, and lenvatinib. Genomic analysis revealed a complex molecular profile that informed this precision therapy approach.
Background
Adrenocortical carcinoma (ACC) is a rare and aggressive tumor with limited treatment options, particularly after conventional therapies fail. The prognosis for metastatic ACC is poor, with a 5-year survival rate of only 10-20%. Recent advances in molecular profiling have opened new avenues for targeted therapies, including immunotherapy, which may improve outcomes in this challenging disease.
Data Highlights
The patient exhibited a remarkable clinical response with the resolution of Cushing’s syndrome and a sustained partial response confirmed by follow-up imaging.
Key Findings
The patient had a complex genomic profile with a high tumor mutational burden of 11.6 mutations/megabase.
Genomic analysis revealed alterations in MSH6, TP53, DAXX, DNMT3A, and KMT2A, indicating instability pathways.
The combination therapy led to the resolution of hypercortisolism and the onset of adrenal insufficiency.
Follow-up imaging showed marked regression of metastatic lesions, evidenced by central photopenia in peritoneal lesions.
This case supports the use of genomic profiling to guide treatment decisions in refractory ACC.
Clinical Implications
The successful use of a combination of pembrolizumab, ipilimumab, and lenvatinib in this case highlights the potential for precision medicine in treating advanced ACC. Clinicians should consider genomic profiling to identify suitable candidates for combination immunotherapy in refractory cases.
Conclusion
This case underscores the importance of genomic analysis in guiding treatment strategies for advanced adrenocortical carcinoma, demonstrating that combination immunotherapy can yield significant clinical benefits.
