Safety and effectiveness of combination versus monotherapy with immune checkpoint inhibitors in patients with preexisting autoimmune diseases

Patients with preexisting autoimmune disease (pAID) are generally excluded from clinical trials for immune checkpoint inhibitors (ICIs) for cancer due to concern of flaring pAID. In this multi-center, retrospective observational study, we compared safety of ICI combination (two ICI agents) versus mo...

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Main Authors: Pankti Reid, Sabina Sandigursky, Juhee Song, Maria A. Lopez-Olivo, Houssein Safa, Samuel Cytryn, Elizaveta Efuni, Maryam Buni, Anna Pavlick, Michelle Krogsgaard, Osama Abu-Shawer, Mehmet Altan, Jeffrey S. Weber, Osama E. Rahma, Maria E. Suarez-Almazor, Adi Diab, Noha Abdel-Wahab
Format: Article
Language:English
Published: Taylor & Francis Group 2023-12-01
Series:OncoImmunology
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Online Access:https://www.tandfonline.com/doi/10.1080/2162402X.2023.2261264
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author Pankti Reid
Sabina Sandigursky
Juhee Song
Maria A. Lopez-Olivo
Houssein Safa
Samuel Cytryn
Elizaveta Efuni
Maryam Buni
Anna Pavlick
Michelle Krogsgaard
Osama Abu-Shawer
Mehmet Altan
Jeffrey S. Weber
Osama E. Rahma
Maria E. Suarez-Almazor
Adi Diab
Noha Abdel-Wahab
author_facet Pankti Reid
Sabina Sandigursky
Juhee Song
Maria A. Lopez-Olivo
Houssein Safa
Samuel Cytryn
Elizaveta Efuni
Maryam Buni
Anna Pavlick
Michelle Krogsgaard
Osama Abu-Shawer
Mehmet Altan
Jeffrey S. Weber
Osama E. Rahma
Maria E. Suarez-Almazor
Adi Diab
Noha Abdel-Wahab
author_sort Pankti Reid
collection DOAJ
description Patients with preexisting autoimmune disease (pAID) are generally excluded from clinical trials for immune checkpoint inhibitors (ICIs) for cancer due to concern of flaring pAID. In this multi-center, retrospective observational study, we compared safety of ICI combination (two ICI agents) versus monotherapy in cancer patients with pAIDs. The primary outcome was time to AEs (immune-related adverse events (irAEs) and/or pAID flares), with progression-free survival (PFS) and overall survival as secondary outcomes. Sixty-four of 133 patients (48%) received ICI combination and 69 (52%) monotherapy. Most had melanoma (32%) and lung cancer (31%). Most common pAIDs were rheumatic (28%) and dermatologic (23%). Over a median follow-up of 15 months (95%CI, 11-18 mo), the cumulative incidence of any-grade irAEs was higher for combination compared to monotherapy (subdistribution hazard ratio (sHR) 2.27, 95%CI 1.35–3.82). No statistically significant difference was observed in high-grade irAEs (sHR 2.31 (0.95–5.66), P = .054) or the cumulative incidence of pAID flares. There was no statistically significant difference for melanoma PFS between combination versus monotherapy (23.2 vs. 17.1mo, P = .53). The combination group was more likely to discontinue or hold ICI, but > 50% of the combination group was still able to continue ICI therapy. No treatment-related deaths occurred. In our cohort with pAIDs, patients had a tolerable toxicity profile with ICI combination therapy. Our results support the use of ICI combination if deemed necessary for cancer therapy in patients with pAIDs, since the ICI toxicities were comparable to monotherapy, able to be effectively managed and mostly did not require ICI interruption.
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spelling doaj-art-e9e4bf95dfc442469304d1d2730ac3042025-08-20T02:01:30ZengTaylor & Francis GroupOncoImmunology2162-402X2023-12-0112110.1080/2162402X.2023.2261264Safety and effectiveness of combination versus monotherapy with immune checkpoint inhibitors in patients with preexisting autoimmune diseasesPankti Reid0Sabina Sandigursky1Juhee Song2Maria A. Lopez-Olivo3Houssein Safa4Samuel Cytryn5Elizaveta Efuni6Maryam Buni7Anna Pavlick8Michelle Krogsgaard9Osama Abu-Shawer10Mehmet Altan11Jeffrey S. Weber12Osama E. Rahma13Maria E. Suarez-Almazor14Adi Diab15Noha Abdel-Wahab16Division of Rheumatology, Department of Medicine, University of Chicago Medical Center, Chicago, IL, USADivision of Rheumatology, Department of Medicine, NYU Langone Health, New York, NY, USADepartment of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Health Services Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USADivision of Internal Medicine, Department of Medicine, NYU Langone Health, New York, TX, USADivision of Internal Medicine, Department of Medicine, NYU Langone Health, New York, TX, USASection of Rheumatology and Clinical Immunology, Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USAMedical Oncology, Weill Cornell Medical Center, New York, NY, USAPerlmutter Cancer Center, Department of Pathology, NYU Langone Health, New York, NY, USADepartment of Internal Medicine, Harvard Medical School, Boston, MA, USADepartment of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USAPerlmutter Cancer Center, Department of Medicine, NYU Langone Health, New York, NY, USADepartment of Internal Medicine, Harvard Medical School, Boston, MA, USADepartment of Health Services Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USAPatients with preexisting autoimmune disease (pAID) are generally excluded from clinical trials for immune checkpoint inhibitors (ICIs) for cancer due to concern of flaring pAID. In this multi-center, retrospective observational study, we compared safety of ICI combination (two ICI agents) versus monotherapy in cancer patients with pAIDs. The primary outcome was time to AEs (immune-related adverse events (irAEs) and/or pAID flares), with progression-free survival (PFS) and overall survival as secondary outcomes. Sixty-four of 133 patients (48%) received ICI combination and 69 (52%) monotherapy. Most had melanoma (32%) and lung cancer (31%). Most common pAIDs were rheumatic (28%) and dermatologic (23%). Over a median follow-up of 15 months (95%CI, 11-18 mo), the cumulative incidence of any-grade irAEs was higher for combination compared to monotherapy (subdistribution hazard ratio (sHR) 2.27, 95%CI 1.35–3.82). No statistically significant difference was observed in high-grade irAEs (sHR 2.31 (0.95–5.66), P = .054) or the cumulative incidence of pAID flares. There was no statistically significant difference for melanoma PFS between combination versus monotherapy (23.2 vs. 17.1mo, P = .53). The combination group was more likely to discontinue or hold ICI, but > 50% of the combination group was still able to continue ICI therapy. No treatment-related deaths occurred. In our cohort with pAIDs, patients had a tolerable toxicity profile with ICI combination therapy. Our results support the use of ICI combination if deemed necessary for cancer therapy in patients with pAIDs, since the ICI toxicities were comparable to monotherapy, able to be effectively managed and mostly did not require ICI interruption.https://www.tandfonline.com/doi/10.1080/2162402X.2023.2261264Preexisting autoimmune diseaseimmune-related adverse eventscancer immunotherapy toxicityautoimmune disease flarecombination immune checkpoint inhibitor
spellingShingle Pankti Reid
Sabina Sandigursky
Juhee Song
Maria A. Lopez-Olivo
Houssein Safa
Samuel Cytryn
Elizaveta Efuni
Maryam Buni
Anna Pavlick
Michelle Krogsgaard
Osama Abu-Shawer
Mehmet Altan
Jeffrey S. Weber
Osama E. Rahma
Maria E. Suarez-Almazor
Adi Diab
Noha Abdel-Wahab
Safety and effectiveness of combination versus monotherapy with immune checkpoint inhibitors in patients with preexisting autoimmune diseases
OncoImmunology
Preexisting autoimmune disease
immune-related adverse events
cancer immunotherapy toxicity
autoimmune disease flare
combination immune checkpoint inhibitor
title Safety and effectiveness of combination versus monotherapy with immune checkpoint inhibitors in patients with preexisting autoimmune diseases
title_full Safety and effectiveness of combination versus monotherapy with immune checkpoint inhibitors in patients with preexisting autoimmune diseases
title_fullStr Safety and effectiveness of combination versus monotherapy with immune checkpoint inhibitors in patients with preexisting autoimmune diseases
title_full_unstemmed Safety and effectiveness of combination versus monotherapy with immune checkpoint inhibitors in patients with preexisting autoimmune diseases
title_short Safety and effectiveness of combination versus monotherapy with immune checkpoint inhibitors in patients with preexisting autoimmune diseases
title_sort safety and effectiveness of combination versus monotherapy with immune checkpoint inhibitors in patients with preexisting autoimmune diseases
topic Preexisting autoimmune disease
immune-related adverse events
cancer immunotherapy toxicity
autoimmune disease flare
combination immune checkpoint inhibitor
url https://www.tandfonline.com/doi/10.1080/2162402X.2023.2261264
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