Hyperprogression on immunotherapy with complete response to chemotherapy in a NSCLC patient with high PD-L1 and STK11: A case report

Medicine (Baltimore). 2020 Nov 13;99(46):e22323. doi: 10.1097/MD.0000000000022323.


Rationale: Patients reporting high PD-L1 expression have shown to respond well to immunotherapy; however, some patients develop hyperprogressive disease upon initiation of immune checkpoint inhibitors. We report a patient with lung cancer and 100% PD-L1 expression who developed hyperprogressive disease while treated with pembrolizumab and responded well to salvage chemotherapy with carboplatin and pemetrexed.

Patient concerns: A 66-year-old African American female with 25-pack year smoking history, diabetes mellitus type 2, essential thrombocytosis, and a history of papillary thyroid carcinoma developed relapsed lung adenocarcinoma after 13 months of no evidence of disease.

Diagnosis: Surveillance imagine showed subcarinal and hilar lymphadenopathy, which was confirmed as recurrent lung adenocarcinoma via bronchoscopy. In addition, a brain scan showed a 5 mm enhancing left insular lesion. PD-L1 was reported as 100% expression. Staging was reported as stage IVB TxN3M1c lung adenocarcinoma.

Interventions: One fraction of radiation with a total dose of 20 Gray was delivered to the left insular lesion. The patient initiated pembrolizumab (200 mg) every 3 weeks. She was then treated with salvage chemotherapy consisting of carboplatin (AUC 5) and pemetrexed (500 mg/m) every 3 weeks for 3 cycles.

Outcomes: The brain lesion resolved after the radiation therapy. The patient developed hyperprogression with a large pericardial effusion and right pleural effusion after 2 treatments of pembrolizumab. Her PD-L1 expression decreased from 100% to 0% over a 10-week period. Salvage chemotherapy with carboplatin and pemetrexed resulted with 20 months of ongoing to evidence of disease.

Lessons: Immune checkpoint inhibitor-related hyperprogressive disease may respond to second-line salvage chemotherapy. Complete PD-L1 expression loss was observed after the patient's treatment and could be a marker of hyperprogressive disease or tumor immunoevasion.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • B7-H1 Antigen / analysis*
  • B7-H1 Antigen / genetics
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Drug Therapy / methods
  • Drug Therapy / standards
  • Female
  • Gene Expression / genetics
  • Humans
  • Protein-Serine-Threonine Kinases / analysis*
  • Protein-Serine-Threonine Kinases / genetics


  • Antibodies, Monoclonal, Humanized
  • B7-H1 Antigen
  • CD274 protein, human
  • pembrolizumab
  • STK11 protein, human
  • Protein-Serine-Threonine Kinases