Hyperprogression after immunotherapy

Abstract

Introduction:Checkpoint inhibitors demonstrate very good anticancer effects, and some patients are long-time responders. As our experience to use these drugs increases, we see more and more patients having different kind of side effects which are usually not seen with chemotherapy. We have observed a subset of patients who appear to be “hyper-progressors,” with a greatly accelerated rate of tumor growth and clinical deterioration compared to pretherapy, which was also recently reported by Institut Gustave Roussy.Materials and Methods:Medical records from all patients (N = 50) prospectively treated in our hospital by anti-PD-1/PD-L1 were analyzed. The tumor growth rate (TGR) prior (“REFERENCE;” REF) and upon (“EXPERIMENTAL”; EXP) anti-PD-1/PD-L1 therapy was compared to identify patients with accelerated tumor growth. Associations between TGR and overall survival (OS) were computed.Results:Hyperprogressive disease (HPD) was defined as a RECIST progression at the first evaluation and as a ≥2-fold increase of the TGR between the REF and the EXP periods. Of 50 evaluable patients, four patients (8%) were considered as having HPD. At progression, patients with HPD had a higher rate of new lesions. HPD was associated with a worse outcome (OS).Conclusion:Hyperprogression was seen in 4 of 50 (8%) of patients, three of which had urothelial cancer and one malignant melanoma, treated with anti-PD-1 or anti-PD-L1 monotherapy. Patients, on immunotherapy, qualifying for hyperprogression had shorted OS. It is important to have a better understanding of hyperprogression on immunotherapy which shall be addressed in the ongoing immunotherapy studies.

Definition, Incidence, and Challenges for Assessment of Hyperprogressive Disease During Cancer Treatment With Immune Checkpoint Inhibitors

“… 24 Ten studies included various types of cancer, which limited tumor type–based subgroup analysis. 5 , 8 , 11 , 12 , 14 , 17 , 18 , 25 , 26 , 28 …”

“…independently selected literature eligible for review. Disagreements between the 2 reviewers occurred regarding 2 studies 27 , 28 and were resolved by consensus with 1 of us (S.Y.).…”

“…So far, there have been scattered individual studies exploring HPD with varying definitions. 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 To our knowledge, no attempt has yet been made to generate a more evidence-based systematic summary about definitions and incidence of HPD. Therefore, we aimed to perform a systematic review to summarize the proposed definitions of HPD and reported incidence of HPD, which may help provide a more standardized diagnosis of HPD in patients receiving ICI treatment.…”

Prediction model for hyperprogressive disease in non‐small cell lung cancer treated with immune checkpoint inhibitors

“…Although TNM stage or T stage was not significantly related to HPD development in this study, this was attributed to the advanced disease stages (stage IV and T4) of all HPD patients enrolled in this study. Conversely, several studies have reported no significant association between other markers of tumor burden (sum of the largest diameter of target lesions at baseline, tumor volume at baseline on volumetric measurement) and HPD development 13, 17, 18 . However, these studies had different definitions of HPD and inclusion criteria.…”

“…Conversely, several studies have reported no significant association between other markers of tumor burden (sum of the largest diameter of target lesions at baseline, tumor volume at baseline on volumetric measurement) and HPD development. 13,17,18 However, these studies had different definitions of HPD and inclusion criteria. Therefore, multicenter studies with a consistent design are warranted.…”