1354P - Comparison of different hyperprogressive disease criteria in non-small cell lung cancer patients treated with immunotherapy and correlation with somatic mutations in driver genes

Background

Our group recently found an association between a burst of highly differentiated CD4⁺ cells (CD4 T_HD burst) between the first and second cycle of immunotherapy and hyperprogressive disease (HPD) in a cohort of pretreated non-small cell lung cancer (NSCLC) patients [Arasanz H et al, Cancers (Basel) 2020]. We have expanded this cohort, compared the incidence of HPD using the different radiological criteria and our CD4 T_HD burst, evaluated the outcomes and correlated this information with somatic mutations detected by next-generation sequencing (NGS) in tumor samples.

Methods

We recruited 90 NSCLC patients treated with immune-checkpoint inhibitor (ICI) monotherapy after progression to platinum-based chemotherapy. Lymphocytes were purified by Ficoll gradient before each cycle and analyzed by flow cytometry. HPD was identified by TGK_R ≥ 2 (Sâada-Bouzid E, et al. Ann Oncol 2017), TGR ≥ 2 (Champiat S, 2017), time-to-failure (TTF) ≤ 2 months and CD4 T_HD burst > 1.3 [Arasanz H, et al. Cancers (Basel) 2020)]. Somatic mutations in tumor samples were analyzed using the Oncomine Comprehensive Assay.

Results

72 patients were evaluable for radiological HPD. Incidence was 20.8% by TGK_R and 19.4% by TGR. 79 patients were evaluable for CD4 T_HD burst, and incidence was 21.5%. 40% of patients had time to treatment failure (TTF) ≤ 2 months. HPD was associated with lower PFS (TGK_R 6.3 vs 12.4 wks, p < 0.001; TGR 6.3 vs 10.9 wks, p < 0.001; TTF 5.7 vs 17.3 weeks, p < 0.001; CD4 T_HD 7.0 vs 9.3 wks, p=0.001). Patients with TTF < 2 months had worse OS (15.1 vs 69.6, p < 0.001). A trend was found for TGK_R (23.7 vs 54.7, p=0.1), TGR (18.7 vs 52.4, p=0.1) and CD4 T_HD (13.9 vs 43.9 wks, p=0.09). A strong agreement was found between TGK_R and TGR (κ=0.871), while only fair agreement with CD4 T_HD burst or TTF < 2 months was detected (κ=0.2 - 0.3). TP53 mutations were found in 71% of HPD by TGR and TGK_R, while they were 39% in the rest of the cohort. ARID1A mutations were found in 29% of HPD by TGR and TGK_R, while they were 9% in the rest of the cohort.

Conclusions

The different HPD criteria identified a subgroup of patients with shorter PFS and OS. A strong agreement between TGK_R and TGR was found. TP53 and ARID1A mutations were more frequently detected among HPD patients, although their role in this phenomenon is still unclear.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

IdiSNA.

Funding

Gobierno de Navarra, Direción General de Industria, Energía e Innovación; Asociación Española Contra el Cáncer (AECC).

Disclosure

H. Arasanz: Financial Interests, Personal, Advisory Board: AstraZeneca. All other authors have declared no conflicts of interest.