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

ABSTRACT

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.

KEYWORDS:

• Preexisting autoimmune disease
• immune-related adverse events
• cancer immunotherapy toxicity
• autoimmune disease flare
• combination immune checkpoint inhibitor

Disclosure statement

MK received research support from Merck, Agenus and AgenTus. JW consults for and has received less than $10,000 dollars per annum from Merck, Genentech, Astra Zeneca, GSK, Novartis, Nektar, Medivation, Celldex, Incyte and EMD Serono and $10–25,000 dollars from BMS for membership in Advisory Boards, holds equity in CytoMx, Biond, and Altor, is on a scientific advisory board for Celldex, CytoMx, Incyte, Biond, Protean, CV6, and Sellas, and was named on a patent from the Moffitt Cancer Center on an ipilimumab biomarker and a PD-1 patent from Biodesix.

Dr. Pankti Reid has a patent pending with the University of Chicago for the use of interleukin 6 inhibitors for viral inflammation. Dr. Suarez-Almazor received consultant fees from Bristol Myers Squibb, Pfizer, and Eli Lilly outside the submitted work. Dr. Diab received research funds from Bristol Myers Squibb, Pfizer, Apexigen, Nektar Therapeutics, and Idera Therapeutics. Dr. Abdel-Wahab received consultant fees from ChemoCentryx outside the submitted work. Dr. Abdel-Wahab is supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health Award Number K01AI163412 and by the University of Texas MD Anderson Cancer Center Division of Internal Medicine Research and Quality Improvement Development Award, Division of Internal Medicine Bridge Funding Award, Survivorship Seed Money Award, and an Institutional Research Grant. Statistical analysis was supported in part by a Cancer Center Support Grant (NCI Grant P30 CA016672). Dr. Lopez-Olivo was supported by the National Cancer Institute of the National Institutes of Health Award Number K08CA237819.

Authors’ contributions

Study concept and design: Dr. Reid, Dr. Sandigursky, Dr. Abdel-Wahab

Acquisition of data: Dr. Cytryn, Dr. Efuni, Dr. Safa, Dr. Buni, Dr. Abu-Shawer

Analysis and interpretation of data: Dr. Reid, Dr. Song, Dr. Abdel-Wahab

Quality appraisal: Dr. Reid, Dr. Song, Dr. Abdel-Wahab

Drafting of the manuscript: Dr. Reid, Dr. Sandigursky, Dr. Song, Dr. Abdel-Wahab

Critical revision of the manuscript for important intellectual content: Dr. Lopez-Olivo, Dr. Safa, Dr. Cytryn, Dr. Efuni, Dr. Buni, Dr. Pavlick, Dr. Krogsgaard, Dr. Abu-Shawer, Dr. Altan, Dr. Weber, Dr. Rahma, Dr. Suarez-Almazor, Dr. Diab

Statistical analysis: Dr. Song

Administrative, technical, or material support: Dr. Reid, Dr. Diab, and Dr. Abdel-Wahab

Study supervision: Dr. Reid, Dr. Diab, Dr. Abdel-Wahab

Consent for publication

Informed consent to participate was waived for this study.

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article [and/or] its supplementary materials.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/2162402X.2023.2261264

Additional information

Funding

The work was supported by the National Institutes of Health.