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Prognosis Paradox: Does HLA-B27 Improve the Prognosis of Immune-Related Pneumonitis in Metastatic Lung Cancer?
Background
Immune related adverse events (irAE) are a well-known complication in the treatment of nonsmall cell lung cancer (NSCLCA) with checkpoint inhibitors and have been shown to improve overall survival (OS) and progression free survival (PFS) across multiple studies. However, studies have shown that the prognosis of NSCLCA differs depending on the type of immune related adverse event and the grade of the irAE. For instance, patients who experienced endocrine irAEs like thyroid, or adrenal insufficiency tended to have an improved OS and PFS, whereas patients who developed pneumonitis that required discontinuation of checkpoint inhibitors had worse OS and PFS. While the literature describes the prognostic impacts of irAEs on NSCLCA, there is still a dearth of information on the implications of HLA supertypes on the prognosis of NSCLCA following irAEs.
Case Presentation
To address this point and to ask a question, we would like to share the case of a patient with a 10-year history of inflammatory arthropathy related to HLA-B27 antigen prior to his diagnosis of T2bN2M1b adenosquamous lung cancer with liver metastases. The tumor was 100% PD-L1 expressive and the patient was treated with pembrolizumab. The patient developed central adrenal insufficiency 10 months after pembrolizumab was initiated which was treated with physiologic dosing of hydrocortisone. The patient later developed a grade 3 pneumonitis 62 months after initiation of pembrolizumab and was treated with systemic glucocorticoids. Due to recurrent hospitalizations for pneumonitis, pembrolizumab was discontinued at 70 months post initiation. At the time of discontinuation PET was positive. However, there was a decrease in hyperactivity of the primary tumor at 4 months post discontinuation of pembrolizumab and there have been serial negative PETS from 7 months to 13 months post discontinuation. This led us to ask the question of whether HLA-B27 is protective of the poor prognostic immune related pneumonitis in this patient?
Background
Immune related adverse events (irAE) are a well-known complication in the treatment of nonsmall cell lung cancer (NSCLCA) with checkpoint inhibitors and have been shown to improve overall survival (OS) and progression free survival (PFS) across multiple studies. However, studies have shown that the prognosis of NSCLCA differs depending on the type of immune related adverse event and the grade of the irAE. For instance, patients who experienced endocrine irAEs like thyroid, or adrenal insufficiency tended to have an improved OS and PFS, whereas patients who developed pneumonitis that required discontinuation of checkpoint inhibitors had worse OS and PFS. While the literature describes the prognostic impacts of irAEs on NSCLCA, there is still a dearth of information on the implications of HLA supertypes on the prognosis of NSCLCA following irAEs.
Case Presentation
To address this point and to ask a question, we would like to share the case of a patient with a 10-year history of inflammatory arthropathy related to HLA-B27 antigen prior to his diagnosis of T2bN2M1b adenosquamous lung cancer with liver metastases. The tumor was 100% PD-L1 expressive and the patient was treated with pembrolizumab. The patient developed central adrenal insufficiency 10 months after pembrolizumab was initiated which was treated with physiologic dosing of hydrocortisone. The patient later developed a grade 3 pneumonitis 62 months after initiation of pembrolizumab and was treated with systemic glucocorticoids. Due to recurrent hospitalizations for pneumonitis, pembrolizumab was discontinued at 70 months post initiation. At the time of discontinuation PET was positive. However, there was a decrease in hyperactivity of the primary tumor at 4 months post discontinuation of pembrolizumab and there have been serial negative PETS from 7 months to 13 months post discontinuation. This led us to ask the question of whether HLA-B27 is protective of the poor prognostic immune related pneumonitis in this patient?
Background
Immune related adverse events (irAE) are a well-known complication in the treatment of nonsmall cell lung cancer (NSCLCA) with checkpoint inhibitors and have been shown to improve overall survival (OS) and progression free survival (PFS) across multiple studies. However, studies have shown that the prognosis of NSCLCA differs depending on the type of immune related adverse event and the grade of the irAE. For instance, patients who experienced endocrine irAEs like thyroid, or adrenal insufficiency tended to have an improved OS and PFS, whereas patients who developed pneumonitis that required discontinuation of checkpoint inhibitors had worse OS and PFS. While the literature describes the prognostic impacts of irAEs on NSCLCA, there is still a dearth of information on the implications of HLA supertypes on the prognosis of NSCLCA following irAEs.
Case Presentation
To address this point and to ask a question, we would like to share the case of a patient with a 10-year history of inflammatory arthropathy related to HLA-B27 antigen prior to his diagnosis of T2bN2M1b adenosquamous lung cancer with liver metastases. The tumor was 100% PD-L1 expressive and the patient was treated with pembrolizumab. The patient developed central adrenal insufficiency 10 months after pembrolizumab was initiated which was treated with physiologic dosing of hydrocortisone. The patient later developed a grade 3 pneumonitis 62 months after initiation of pembrolizumab and was treated with systemic glucocorticoids. Due to recurrent hospitalizations for pneumonitis, pembrolizumab was discontinued at 70 months post initiation. At the time of discontinuation PET was positive. However, there was a decrease in hyperactivity of the primary tumor at 4 months post discontinuation of pembrolizumab and there have been serial negative PETS from 7 months to 13 months post discontinuation. This led us to ask the question of whether HLA-B27 is protective of the poor prognostic immune related pneumonitis in this patient?