Case Report: triple therapy with pembrolizumab, ipilimumab, and lenvatinib in mitotane- and radiation-refractory, cortisol-secreting stage IV adrenocortical carcinoma: a genomically guided approach - Takeaways - MDSpire

Case Report: triple therapy with pembrolizumab, ipilimumab, and lenvatinib in mitotane- and radiation-refractory, cortisol-secreting stage IV adrenocortical carcinoma: a genomically guided approach

  • By

  • Afif Nakhleh

  • Ahmad Mahamid

  • Yaniv Yechiel

  • Leonard Saiegh

  • Sagit Zolotov

  • Salomon M. Stemmer

  • May 4, 2026

  • 0 min

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  • 1

    A 54-year-old woman with stage IV adrenocortical carcinoma (ACC) showed resistance to mitotane and radiation therapy after radical adrenalectomy.

  • 2

    Genomic analysis revealed a complex profile with high tumor mutational burden and alterations in key genes associated with hormonal dysregulation and immune resistance.

  • 3

    The patient was treated with a combination of pembrolizumab, ipilimumab, and lenvatinib, resulting in a significant clinical response and resolution of Cushing’s syndrome.

  • 4

    Follow-up imaging confirmed a sustained partial response and metabolic improvement, demonstrating the effectiveness of the triple therapy regimen.

  • 5

    This case highlights the potential of genomic profiling to guide aggressive combination immunotherapy in refractory adrenocortical carcinoma.

Original Source(s)

Case Report: triple therapy with pembrolizumab, ipilimumab, and lenvatinib in mitotane- and radiation-refractory, cortisol-secreting stage IV adrenocortical carcinoma: a genomically guided approach

  • by Afif Nakhleh, Ahmad Mahamid, Yaniv Yechiel, Leonard Saiegh, Sagit Zolotov, Salomon M. Stemmer

  • May 4, 2026

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