Incidence of Skin and Respiratory Immune-Related Adverse Events Correlates With Specific Tumor Types in Patients Treated With Checkpoint Inhibitors
Checkpoint inhibitors (CPIs) increase antitumor activity by unblocking regulators of the immune response. This action can provoke a wide range of immunologic and inflammatory side effects, some of which can be fatal. Recent studies suggest that CPI-induced immune-related adverse events (irAEs) may p...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-01-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2020.570752/full |
| _version_ | 1819051034417299456 |
|---|---|
| author | Lynn M. Rose Hannah A. DeBerg Prakash Vishnu Jason K. Frankel Adarsh B. Manjunath John Paul E. Flores David M. Aboulafia David M. Aboulafia |
| author_facet | Lynn M. Rose Hannah A. DeBerg Prakash Vishnu Jason K. Frankel Adarsh B. Manjunath John Paul E. Flores David M. Aboulafia David M. Aboulafia |
| author_sort | Lynn M. Rose |
| collection | DOAJ |
| description | Checkpoint inhibitors (CPIs) increase antitumor activity by unblocking regulators of the immune response. This action can provoke a wide range of immunologic and inflammatory side effects, some of which can be fatal. Recent studies suggest that CPI-induced immune-related adverse events (irAEs) may predict survival and response. However, little is known about the mechanisms of this association. This study was undertaken to evaluate the influence of tumor diagnosis and preexisting clinical factors on the types of irAEs experienced by cancer patients treated with CPIs. The correlation between irAEs and overall survival (OS) was also assessed. All cancer patients treated with atezolizumab (ATEZO), ipilimumab (IPI), nivolumab (NIVO), or pembrolizumab (PEMBRO) at Virginia Mason Medical Center between 2011 and 2019 were evaluated. irAEs were graded according to the Common Terminology Criteria for Adverse Events (Version 5) and verified independently. Statistical analyses were performed to assess associations between irAEs, pre-treatment factors, and OS. Of the 288 patients evaluated, 59% developed irAEs of any grade, and 19% developed irAEs of grade 3 or 4. A time-dependent survival analysis demonstrated a clear association between the occurrence of irAEs and OS (P < 0.001). A 6-week landmark analysis adjusted for body mass index confirmed an association between irAEs and OS in non-Small Cell Lung Cancer (NSCLC) (P < 0.03). An association between melanoma and skin irAEs (P < 0.01) and between NSCLC and respiratory irAEs (P = 0.03) was observed, independent of CPI administered. Patients with preexisting autoimmune disease experienced a higher incidence of severe irAEs (P = 0.01), but not a higher overall incidence of irAEs (P = 0.6). A significant association between irAEs and OS was observed in this diverse patient population. No correlation was observed between preexisting comorbid conditions and the type of irAE observed. However, a correlation between skin-related irAEs and melanoma and between respiratory irAEs and NSCLC was observed, suggesting that many irAEs are driven by a specific response to the primary tumor. In patients with NSCLC, the respiratory irAEs were associated with a survival benefit. |
| first_indexed | 2024-12-21T11:57:31Z |
| format | Article |
| id | doaj.art-88f695767baf441e8314cd3c5cd60d1f |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-21T11:57:31Z |
| publishDate | 2021-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-88f695767baf441e8314cd3c5cd60d1f2022-12-21T19:04:54ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-01-011010.3389/fonc.2020.570752570752Incidence of Skin and Respiratory Immune-Related Adverse Events Correlates With Specific Tumor Types in Patients Treated With Checkpoint InhibitorsLynn M. Rose0Hannah A. DeBerg1Prakash Vishnu2Jason K. Frankel3Adarsh B. Manjunath4John Paul E. Flores5David M. Aboulafia6David M. Aboulafia7Scientific Administration, Benaroya Research Institute at Virginia Mason, Seattle, WA, United StatesSystems Immunology, Benaroya Research Institute at Virginia Mason, Seattle, WA, United StatesDivision of Hematology, CHI Franciscan Medical Group, Seattle, WA, United StatesSection of Urology, Virginia Mason Medical Center, Seattle, WA, United StatesSystems Immunology, Benaroya Research Institute at Virginia Mason, Seattle, WA, United StatesDepartment of Hematology and Oncology, Virginia Mason Medical Center, Seattle, WA, United StatesDepartment of Hematology and Oncology, Virginia Mason Medical Center, Seattle, WA, United StatesDivision of Hematology, University of Washington, Seattle, WA, United StatesCheckpoint inhibitors (CPIs) increase antitumor activity by unblocking regulators of the immune response. This action can provoke a wide range of immunologic and inflammatory side effects, some of which can be fatal. Recent studies suggest that CPI-induced immune-related adverse events (irAEs) may predict survival and response. However, little is known about the mechanisms of this association. This study was undertaken to evaluate the influence of tumor diagnosis and preexisting clinical factors on the types of irAEs experienced by cancer patients treated with CPIs. The correlation between irAEs and overall survival (OS) was also assessed. All cancer patients treated with atezolizumab (ATEZO), ipilimumab (IPI), nivolumab (NIVO), or pembrolizumab (PEMBRO) at Virginia Mason Medical Center between 2011 and 2019 were evaluated. irAEs were graded according to the Common Terminology Criteria for Adverse Events (Version 5) and verified independently. Statistical analyses were performed to assess associations between irAEs, pre-treatment factors, and OS. Of the 288 patients evaluated, 59% developed irAEs of any grade, and 19% developed irAEs of grade 3 or 4. A time-dependent survival analysis demonstrated a clear association between the occurrence of irAEs and OS (P < 0.001). A 6-week landmark analysis adjusted for body mass index confirmed an association between irAEs and OS in non-Small Cell Lung Cancer (NSCLC) (P < 0.03). An association between melanoma and skin irAEs (P < 0.01) and between NSCLC and respiratory irAEs (P = 0.03) was observed, independent of CPI administered. Patients with preexisting autoimmune disease experienced a higher incidence of severe irAEs (P = 0.01), but not a higher overall incidence of irAEs (P = 0.6). A significant association between irAEs and OS was observed in this diverse patient population. No correlation was observed between preexisting comorbid conditions and the type of irAE observed. However, a correlation between skin-related irAEs and melanoma and between respiratory irAEs and NSCLC was observed, suggesting that many irAEs are driven by a specific response to the primary tumor. In patients with NSCLC, the respiratory irAEs were associated with a survival benefit.https://www.frontiersin.org/articles/10.3389/fonc.2020.570752/fullcheckpoint inhibitorsimmunotherapyimmune-related adverse eventsbiomarkerssurvival benefitspreexisting conditions |
| spellingShingle | Lynn M. Rose Hannah A. DeBerg Prakash Vishnu Jason K. Frankel Adarsh B. Manjunath John Paul E. Flores David M. Aboulafia David M. Aboulafia Incidence of Skin and Respiratory Immune-Related Adverse Events Correlates With Specific Tumor Types in Patients Treated With Checkpoint Inhibitors Frontiers in Oncology checkpoint inhibitors immunotherapy immune-related adverse events biomarkers survival benefits preexisting conditions |
| title | Incidence of Skin and Respiratory Immune-Related Adverse Events Correlates With Specific Tumor Types in Patients Treated With Checkpoint Inhibitors |
| title_full | Incidence of Skin and Respiratory Immune-Related Adverse Events Correlates With Specific Tumor Types in Patients Treated With Checkpoint Inhibitors |
| title_fullStr | Incidence of Skin and Respiratory Immune-Related Adverse Events Correlates With Specific Tumor Types in Patients Treated With Checkpoint Inhibitors |
| title_full_unstemmed | Incidence of Skin and Respiratory Immune-Related Adverse Events Correlates With Specific Tumor Types in Patients Treated With Checkpoint Inhibitors |
| title_short | Incidence of Skin and Respiratory Immune-Related Adverse Events Correlates With Specific Tumor Types in Patients Treated With Checkpoint Inhibitors |
| title_sort | incidence of skin and respiratory immune related adverse events correlates with specific tumor types in patients treated with checkpoint inhibitors |
| topic | checkpoint inhibitors immunotherapy immune-related adverse events biomarkers survival benefits preexisting conditions |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2020.570752/full |
| work_keys_str_mv | AT lynnmrose incidenceofskinandrespiratoryimmunerelatedadverseeventscorrelateswithspecifictumortypesinpatientstreatedwithcheckpointinhibitors AT hannahadeberg incidenceofskinandrespiratoryimmunerelatedadverseeventscorrelateswithspecifictumortypesinpatientstreatedwithcheckpointinhibitors AT prakashvishnu incidenceofskinandrespiratoryimmunerelatedadverseeventscorrelateswithspecifictumortypesinpatientstreatedwithcheckpointinhibitors AT jasonkfrankel incidenceofskinandrespiratoryimmunerelatedadverseeventscorrelateswithspecifictumortypesinpatientstreatedwithcheckpointinhibitors AT adarshbmanjunath incidenceofskinandrespiratoryimmunerelatedadverseeventscorrelateswithspecifictumortypesinpatientstreatedwithcheckpointinhibitors AT johnpauleflores incidenceofskinandrespiratoryimmunerelatedadverseeventscorrelateswithspecifictumortypesinpatientstreatedwithcheckpointinhibitors AT davidmaboulafia incidenceofskinandrespiratoryimmunerelatedadverseeventscorrelateswithspecifictumortypesinpatientstreatedwithcheckpointinhibitors AT davidmaboulafia incidenceofskinandrespiratoryimmunerelatedadverseeventscorrelateswithspecifictumortypesinpatientstreatedwithcheckpointinhibitors |