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

Abstract

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 2 ) 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.

MYO10 drives genomic instability and inflammation in cancer

“…The exact mechanisms underlying ICB’s hyperprogression are poorly understood and likely context dependent. For instance, loss of programmed cell death ligand 1 (PD-L1) or Serine/Threonine kinase 11 (STK11) ( 70 ) or the presence of epidermal growth factor receptor mutation and MDM proto-oncogene 2/4 (MDM2/4) amplification ( 71 ) were reported to induce anti–PD-1 hyperprogression. The mechanisms by which PyMT/Myo10 +/− tumors grew larger in the presence of anti–PD-1 were probably related to the altered tumor microenvironment (e.g., reduced and increased secretion of Ifn α and Tnfα, respectively, and less infiltrating T cells).…”

Liquid biopsy on the horizon in immunotherapy of non-small cell lung cancer: current status, challenges, and perspectives

“…First, the screening of the immunotherapy beneficiary population using PD-L1 expression is not entirely accurate. Some patients with high PD-L1 expression do not benefit from ICI therapy in clinic [ 40 , 41 ], while patients who do not express PD-L1 may respond to this therapy [ 42 ]. In addition, PD-L1 can be expressed in both tumor cells and immune cells and there is intratumoral and spatiotemporal heterogeneity, and its detection is influenced by subjective interpretation and lack of standardization across different platforms.…”

Hyperprogression under immunotherapy: a new form of immunotherapy response?—a narrative literature review

“…Subsequently, an increasing number of studies have confirmed the existence of the HPD phenomenon in many types of tumors, like NSCLC, esophageal squamous carcinoma, melanoma, soft tissue sarcoma, etc. (8)(9)(10)(11). HP has become an increasingly recognized phenomenon.…”