0757: Safety and Effectiveness of Immune Checkpoint Inhibitors Combination versus Single Agent Therapy in Patients with Pre-existing Autoimmune Diseases

Pankti Reid¹, Sabina Sandigursky², Maria A. Lopez-Olivo³, Juhee Song⁴, Houssein Safa⁵, Samuel Cytryn⁶, Maryam Buni⁷, Anna Pavlick⁸, Michelle Krogsgaard, PhD⁹, Osama Abu-Shawer¹⁰, Mehmet Altan¹¹, Jeffrey Weber¹², Maria Suarez-Almazor¹³, Adi Diab¹⁴ and Noha Abdel-Wahab¹⁴, ¹University of Chicago Medical Center, Chicago, IL, ²NYU Langone Health, New York, NY, ³The University of Texas, MD Anderson Cancer Center, Houston, TX, ⁴The University of Texas MD Anderson Cancer Center, Houston, TX, ⁵Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, ⁶Memorial Sloan Kettering Cancer Center, New York, NY, ⁷MD Anderson Cancer Center, Bellaire, TX, ⁸Medical Oncology, Weill Cornell Medical Center, New York, NY, ⁹Perlmutter Cancer Center, Department of Pathology, NYU Langone Health, New York, NY, ¹⁰Cleveland Clinic Foundation, Cleveland, OH, ¹¹Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, ¹²NYU Langone Medical Center, Laura and Isaac Perlmutter Cancer Center, New York, NY, ¹³MD Anderson Cancer Center, Houston, TX, ¹⁴UT MD Anderson Cancer Center, Houston, TX

Background/Purpose: Treatment with a combination of immune checkpoint inhibitors (ICI) has promising outcomes in many tumor types but carries higher adverse event risk than ICI monotherapy. Also, patients with pre-existing autoimmune disease (AID) have largely been excluded from ICI clinical trials due to concern for pre-existing AID flare or immune-related adverse events (irAEs). This is the first study to analyze safety and effectiveness of ICI combination versus monotherapy for this at-risk population.

Methods: We conducted a multi-center retrospective study in patients with pre-existing AIDs receiving ICIs (i.e., anti-programmed cell death protein 1 (PD-1) single-agent (monotherapy) or ICI combination). Primary endpoints included the time to occurrence of any-type ICI AE (irAE or AID flare), time to irAEs and time to AID flares in the presence of the competing risk of death with progression free survival (PFS, time to progression or death) and overall survival (OS) as secondary endpoints. We used Fine-Gray models and Cox regression models to investigate the factors associated with these endpoints.

Results: 133 patients with pre-existing AID who received ICIs were identified: 69 (52%) monotherapy and 64 (48%) combination (Table 1). About half the patients had melanoma (44%) and 25% had lung cancer. Rheumatic (34%) or dermatologic (22%) pre-existing AIDs were the most common. Most patients (95%) had controlled autoimmune disease at ICI start. Six of 7 patients with active AID at baseline experienced some AE. Patients receiving baseline DMARD(s) were more likely to experience an AE (95%CI 1.079-2.996, p=0.024). The cumulative incidence of irAEs was higher for ICI combination compared to monotherapy (subdistribution hazard ratio (sHR) 2.28, 95%CI 1.36-3.84), adjusting for age at malignancy, but there was no significant difference between rate of high-grade toxicity for patients treated with ICI combination versus monotherapy (See Figure 1). On subgroup analysis for patients with melanoma or lung cancer, the cumulative incidence of irAEs or AID flares were not statistically different between treatment groups. PFS was longer (but not statistically significant) for combination therapy for any tumor type compared to single agent (median 12.3mo, 95%CI 5.0-23.2 versus 7.3mo, 95%CI 5.2-11.3, p=0.116). Similar trend was noted for PFS for melanoma (median 23.2mo combination vs. 14.0mo monotherapy, p=0.4237), while the opposite relation was noted for lung cancer subgroup (4.4mo combination vs. 7.1mo monotherapy, p=0.2933).

Conclusion: Efficacy of ICI combination versus monotherapy was not statistically significant and so still remains unclear in this patient population, but there was no significant difference in rates of high-grade toxicity between the two cohorts. Our data supports the notion that patients with pre-existing AIDs should not be indiscriminately precluded from getting ICI combination. Our results provide guidance for future prospective clinical trials studying combination therapy for subgroups of this at-risk population.


No statistically significant difference appreciated in high grade adverse events between patients with pre-existing autoimmune disease treated with ICI combination versus monotherapy. Grading determined by the Common Terminology Criteria for Adverse Events rubric with grade 3 or higher considered "high grade."
Disclosures: P. Reid, provisional patent; S. Sandigursky, Regeneron Pharmaceuticals; M. Lopez-Olivo, None; J. Song, None; H. Safa, None; S. Cytryn, None; M. Buni, None; A. Pavlick, Bristol-Myers Squibb(BMS), Merck/MSD, Replimune, Regeneron, Bristol-Myers Squibb(BMS); M. Krogsgaard, PhD, Genentech, Merck/MSD, Roche, Neximmune; O. Abu-Shawer, None; M. Altan, GlaxoSmithKlein(GSK), Shattuck Lab, Bristol-Myers Squibb(BMS), AstraZeneca, Intervenn, Nektar therapeutics, SITC; J. Weber, Merck/MSD, Genentech, AstraZeneca, GSK, Novartis, Nektar, Celldex, Incyte, Biond, ImCheck, Sellas, Pfizer, Regeneron, Evaxion, EMD Serono, BMS, OncoC4, InstilBio, Neximmune, Moffitt Cancer Center, Biodesix; M. Suarez-Almazor, Eli Lilly, Pfizer, Celgene, ChemoCentryx, Gilead; A. Diab, None; N. Abdel-Wahab, None.