1058P - Hyperprogressive disease during immune checkpoint inhibitor: A cloudy phenomenon with real consequences

Background

Hyperprogressive disease (HPD) is a potentially fatal complication arising from immune checkpoint inhibitor (ICI) therapy. It was described as an explosion in tumor growth, faster than the natural kinetic of the disease would predict. This manifestation remains poorly understood and subject of debate, with highly variable incidence between studies, reflecting the absence of a consensual definition. Our objective was to study, in a real-life setting, the incidence of HPD and factors associated with survival of HPD patients.

Methods

The HYPERPROG study is a national, multicentric, retrospective analysis utilizing the ConSoRe data mining tool (Continuum Soins Recherche). HPD was defined as an increase of more than 100% in tumor growth rate between the pre-ICI CT-scan and the first re-evaluation by CT-scan, together with clinical deterioration. Patients, tumor characteristics and biological variables were collected and tested for overall survival (OS) association using log-rank test and Cox model.

Results

Among the 13,250 patients treated by ICI for any tumor type and stage between 2016 and 2023 in four cancer centers, 57 met the pre-cited definition of HPD, leading to an incidence of HPD around 0.5%. HPD was observed exclusively in metastatic (87.7%) and locally advanced (12.3%) disease, with no case in neo-adjuvant setting. HPD typically manifested early, with 53% of cases occurring within the first two ICI infusions and 74% exhibiting clinical deterioration prior to scheduled CT evaluations. The median OS for HPD patients was four months, with an 86% mortality rate at 12 months. The mains HPD territories were primitive site, lung and liver. Significant predictors of poorer OS included a neutrophil-to-lymphocyte ratio (NLR) greater than 4 (HR = 1.7 [0.98; 3.1]), male gender (HR = 2.2 [1.1; 4.5]), a Charlson comorbidity index greater than 10 (HR = 2 [1; 3.9]), and the presence of brain metastases prior to starting ICI (HR = 5.45 [1.9; 13.3]).

Conclusions

HPD is a rare but serious adverse event that need to be considered in the face of any clinical deterioration in the first 4 months of ICI and must motivate rapid imaging confirmation without waiting for programmed tumor evaluation.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Institut Paoli-Calmettes.

Funding

Has not received any funding.

Disclosure

N. Girard: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, MSD, Roche, Pfizer, Mirati, Amgen, Novartis, Sanofi, Gilead; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Boehringer, Novartis, Sanofi, AbbVie, Amgen, Lilly, Grunenthal, Takeda, Owkin, Leo Pharma, Daiichi Sankyo, Ipsen; Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen; Financial Interests, Institutional, Funding: BMS, Leo Pharma; Financial Interests, Institutional, Research Grant: MSD; Other, Family member is an employee: AstraZeneca. N. Penel: Financial Interests, Institutional, Research Grant, Research grant for clinical trials in sarcoma filed: Bayer HealthCare. A. Gonçalves: Financial Interests, Institutional, Advisory Board: AstraZeneca, Novartis, MSD, Innate Pharma, Parexel, Gilead; Financial Interests, Institutional, Local PI: Novartis, AstraZeneca, Daiichi Sankyo; Financial Interests, Institutional, Coordinating PI: Roche, MSD; Other, travel, accommodation, meeting registration: Mylan, Novartis, Roche, Menarini. G. Gravis: Financial Interests, Institutional, Invited Speaker: AAA, Amgen, Astellas, BMS, Janssen, MSD, Pfizer, Ipsen, AstraZeneca, Alliance Merck Pfizer, Bayer, Eisai; Financial Interests, Institutional, Advisory Board: Alliance Merck-Pfizer, BMS, Janssen, Pfizer, Ipsen, Bayer, Eisai; Financial Interests, Institutional, Funding: Janssen; Financial Interests, Institutional, Coordinating PI: BMS; Non-Financial Interests, Principal Investigator: Ipsen, BMS, Merck. All other authors have declared no conflicts of interest.