Case Report: triple therapy with pembrolizumab, ipilimumab, and lenvatinib in mitotane- and radiation-refractory, cortisol-secreting stage IV adrenocortical carcinoma: a genomically guided approach - Scorecard - 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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Clinical Scorecard: Clinical Case Study: Utilizing a Combination of Pembrolizumab, Ipilimumab, and Lenvatinib for Stage IV Adrenocortical Carcinoma Resistant to Mitotane and Radiation Therapy: A Genomic-Based Strategy

At a Glance

CategoryDetail
Condition
Key MechanismsGNAS activation, HSD11B2 modification, high tumor mutational burden, genomic instability pathways (MSH6, TP53, DAXX, DNMT3A, KMT2A alterations)
Target Population
Care Setting

Key Highlights

  • Patient exhibited a remarkable clinical response to triple therapy
  • Genomic analysis revealed complex molecular profile and high TMB
  • Combination therapy included pembrolizumab, ipilimumab, and lenvatinib
  • Sustained partial response confirmed by RECIST 1.1 and metabolic imaging
  • Addressed cortisol-induced immune suppression through aggressive treatment

Guideline-Based Recommendations

Diagnosis

    Management

      Monitoring & Follow-up

      • Regular follow-up with 18F-FDG PET/CT scans
      • Monitor biochemical markers for Cushing's syndrome resolution (e.g., urinary free cortisol, ACTH levels)

      Risks

        Patient & Prescribing Data

        Combination therapy led to resolution of Cushing's syndrome and partial tumor response; patient previously treated with mitotane and radiation.

        Clinical Best Practices

        • Implement comprehensive genomic profiling in treatment planning
        • Utilize combination therapies to overcome resistance mechanisms
        • Monitor for adverse effects and adjust treatment accordingly
        • Select patients for combination therapies based on genomic profiling results

        References

        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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