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Case report: A persistently expanded T cell response in an exceptional responder to radiation and atezolizumab for metastatic non-small cell lung cancer.

ABSTRACT: Most patients with advanced non-small cell lung cancer (NSCLC) do not achieve a durable remission after treatment with immune checkpoint inhibitors. Here we report the clinical history of an exceptional responder to radiation and anti-program death-ligand 1 (PD-L1) monoclonal antibody, atezolizumab, for metastatic NSCLC who remains in a complete remission more than 8 years after treatment. Sequencing of the patient's T cell repertoire from a metastatic lesion and the blood before and after anti-PD-L1 treatment revealed oligoclonal T cell expansion. Characterization of the dominant T cell clone, which comprised 10% of all clones and increased 10-fold in the blood post-treatment, revealed an activated CD8⁺ phenotype and reactivity against 4 HLA-A2 restricted neopeptides but not viral or wild-type human peptides, suggesting tumor reactivity. We hypothesize that the patient's exceptional response to anti-PD-L1 therapy may have been achieved by increased tumor immunogenicity promoted by pre-treatment radiation therapy as well as long-term persistence of oligoclonal expanded circulating T cells.

SUBMITTER: Coffey DG

PROVIDER: S-EPMC9500393 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Case report: A persistently expanded T cell response in an exceptional responder to radiation and atezolizumab for metastatic non-small cell lung cancer.

Coffey David G DG Xu Yuexin Y Towlerton Andrea M H AMH Kowanetz Marcin M Hegde Priti P Darwish Martine M Yadav Mahesh M Blanchette Craig C Ruppert Shannon M SM Bertino Sarah S Xu Qikai Q Ferretti Andrew A Weinheimer Adam A Hellmann Matthew M Qin Angel A Thomas Dafydd D Warren Edus H EH Ramnath Nithya N

Frontiers in immunology 20220909

Most patients with advanced non-small cell lung cancer (NSCLC) do not achieve a durable remission after treatment with immune checkpoint inhibitors. Here we report the clinical history of an exceptional responder to radiation and anti-program death-ligand 1 (PD-L1) monoclonal antibody, atezolizumab, for metastatic NSCLC who remains in a complete remission more than 8 years after treatment. Sequencing of the patient's T cell repertoire from a metastatic lesion and the blood before and after anti- ...[more]

PMID: 36159875

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Project description:Among the several next-generation tyrosine kinase inhibitors (TKIs) tested against uncommon EFGR alterations, poziotinib has been demonstrated to be a powerful agent for metastatic non-small-cell lung cancer (mNSCLC) with aberrations in HER2 exon 20, and FDA approval is being sought in the previously-treated population. Poziotinib has also shown activity in mNSCLC with aberrations in EGFR exon 20. Herein, we report the first published case of a patient affected by mNSCLC harbouring an EGFR exon 20 insertion (EGFRex20ins) mutation who achieved a complete response (CR) under treatment with poziotinib as part of the ZENITH20 trial. In January 2021, a former smoker 62-year-old female patient was diagnosed with relapse, after two surgeries and post-operative chemotherapy of mNSCLC, at liver and retroperitoneal nodes. Given the identification by Next Generation Sequencing (NGS) of EGFRex20ins mutation, she was enrolled in ZENITH20-cohort 5 trial, a phase 2 multicentre study aimed to assess the efficacy and safety of poziotinib in patients with EGFR or HER2 exon 20 insertion mutations. Poziotinib as first-line systemic therapy for metastatic disease was initiated at the end of January 2021 and administrated at the initial dosage of 8 mg orally twice daily (BID). The most common side effects from the beginning of the treatment included alopecia, macular skin rash, diarrhoea, xerostomia, and conjunctivitis. Due to these adverse events, poziotinib was discontinued during the first 3 months and then reduced to 6 mg orally BID in April 2021. After the dose de-escalation, the adverse events ameliorated, and the patient better tolerated the treatment without further interruption. Since the first reevaluation (after 4 weeks of therapy), the treatment with poziotinib resulted to be remarkably effective, with a partial response (PR) subsequently confirmed in May and July 2021. Then, in October 2021, a CT scan confirmed a CR, maintained with good tolerance at the last reevaluation in February 2022. Treatment is still ongoing at the same dosage. In this case, poziotinib has represented a successful and well-tolerated first-line treatment alternative to chemotherapy in this patient with EGFR exon 20 insertion mutated mNSCLC.

Project description:BackgroundImmune checkpoint inhibitors (ICIs), an enormous oncological breakthrough in the last 10 years, have become the standard treatments for several types of solid cancers. Although ICIs are generally well tolerated and result in favorable outcomes, they also cause unique immune-related adverse events (irAEs) across bodily systems and organs. Compared to most common irAEs, which occur in the endocrine, skin, pulmonary system, and gastrointestinal tract, haematological irAEs (haem-irAEs) are relatively rare but potentially life-threatening events that are occasionally irreversible and refractory. Currently, haem-irAEs are not sufficiently understood, management, and lack consensus, while other common irAEs have well been characterized and managed. The reports of ICI-related thrombocytopenia in small cell lung cancer (SCLC) are rarely seen. Hence, we reported a rare case of severe steriod-resistant ICI-related thrombocytopenia after received chemotherapy plus anti-PD-L1 inhibitor in SCLC patient. Our case exemplifies the diagnosis, diagnosis of exclusion, treatment, and prognosis of thrombocytopenia in the pattern of combination therapy, meanwhile, the subject of diagnosis, therapies, therapeutic strategies for refractory type and incidence, potential biomarkers, mechanisms and prognosis in ICI-related thrombocytopenia have been fully discussed.Case descriptionHerein, we present a 64-year-old man diagnosed advanced SCLC developed refractory immune-related severe thrombocytopenia, who achieved favorable outcomes of cancer following chemotherapy combined with atezolizumab administrated. Routine blood re-examination on the third day of 6th therapy showed a thrombocyte count of 11×109/L. Combined the medical history and the results of laboratory tests, the diagnosis of ICI-induced thrombocytopenia was confirmed. Despite large doses of methylprednisolone, immunoglobulin, and rituximab, intermittent platelet transfusion, thrombopoietin being administrated to the patient, there were no signs of platelet count and hemoglobin improvement. Currently, this is the first case about atezolizumab induced thrombocytopenia in SCLC patient, while there is extremely rare haem-irAEs reported in SCLC.ConclusionsAlthough ICI-related severe thrombocytopenia is rare, it may persist or even be fatal. Clinicians should pay more attention to its diagnosis and prompt treatment. Once developed thrombocytopenia, large doses of methylprednisolone, ntermittent platelet transfusion, thrombopoietin should be timely administrated, also plasma exchange or rilzabrutinib, other immunosuppressive drugs, or IL-6 inhibitor warrant apply if steriod-resistant.

Dataset Information

Case report: A persistently expanded T cell response in an exceptional responder to radiation and atezolizumab for metastatic non-small cell lung cancer.

Publications

Case report: A persistently expanded T cell response in an exceptional responder to radiation and atezolizumab for metastatic non-small cell lung cancer.

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