Proposal for multiple new lesions as complement of hyperprogressive disease in NSCLC patients treated with PD-1/PD-L1 immunotherapy

Abstract

BackgroundHyperprogressive disease (HPD) is a progression pattern of rapid increase in tumor burden during immunotherapy. However, current HPD definitions are mainly based on the diameter of target lesions. How to take new lesions into account remains unknown. MethodsIn this retrospectively analysis, 393 patients received PD-1/PD-L1 inhibitors monotherapy. 237 patients were eligible for HPD evaluation based on tumor growth rate (TGR) ratio, ΔTGR or tumor growth kinetic (TGK) ratio. Among them, 214 patients were eligible for evaluation of new lesions. The impact of new lesions on overall survival (OS) was investigated by Kaplan-Meier methods. The optimal threshold for new lesion number was investigated by one-year time-dependent receiver operating characteristic (ROC) curves. Developing more than one new lesions (n ≥ 2) was defined as multiple new lesions (MNL). New HPD was redefined as both developing MNL and meeting the requirement of current HPD definitions (TGR ratio, ΔTGR or TGK ratio). The survival difference between the newly defined HPD and non-HPD patients was investigated. ResultsHPD occurred in 5.1–18.1 % patient based on current definitions (TGR ratio, 15.6 %; ΔTGR, 5.1 %; TGK ratio, 18.1 %). However, there is no significant difference between OS of HPD and non-HPD patient. New lesion was associated with a shorter median OS in PD（with or without HPD) patients (6.1 vs 18.9 months, p = 0.001). Time-dependent ROC analysis suggested that the optimal threshold for new lesion number in survival prediction was two. After the redefinition of HPD, New HPD patients had a significantly shorter median OS compared with non-HPD patients (TGR ratio with MNL: 5.6 vs 11.8 months, p < 0.001; ΔTGR with MNL: 5.0 vs 11.4 months, p = 0.034; TGK ratio with MNL: 5.7 vs 12.3 months, p < 0.001; respectively). ConclusionsCurrent HPD definitions had a better prognostic value when complemented with MNL. MNL should be integrated into the new definition of HPD.