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1407 Understanding the definition of hyperprogressive disease (HPD) and its incidence – a new path forward
  1. Trie Arni Djunadi1,
  2. Youjin Oh1,
  3. Liam Il-Young Chung1,
  4. Timothy Hong2,
  5. Soowon Lee3,
  6. Zunairah Shah1,
  7. Joo Hee Park1,
  8. Sung Mi Yoon1 and
  9. Young Kwang Chae1
  1. 1Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
  2. 2Northwestern University, Evanston, IL, USA
  3. 3Baylor University, Waco, TX, USA


Background Hyperprogressive disease (HPD) is a phenomenon where tumors grow exponentially following immunotherapy. Multiple definitions have been proposed, and the incidence of HPD varies from 5.9% to 43.1% depending on the definition.1 As HPD is associated with worse patient outcomes, it is important to have a clear definition of HPD to identify and prevent such cases.2,3 There is much discussion about how to best define HPD as RECIST criteria only considers the target lesions.4 iRECIST and irRECIST have been newly proposed to incorporate new lesions. This study proposes a new, modified definition for HPD using RECIST 1.1 and taking the sum of new lesions into consideration.

Methods This study retrospectively analyzed 128 lung cancer patients‘ data (N of patients = 128) and 144 total number of regimens (N of regimens = 144) at a large metropolitan academic medical center. This study compares the incidence of hyperprogression using different definitions including Champiat, Saada-Bouzid, and Ferrara et al.5-7 As a modification to these definitions, the new lesions were included into the sum of lesions. The difference of incidence between original and modified definitions was evaluated with Chi-squared test.

Results The incidence rate of hyperprogression ranged from 5% to 15%, depending on the original definitions and modified definitions. Among the 144 treatment regimens, hyperprogression was detected in 5% (N=7), 10% (N=14), and 0% (N=0) using the original Champiat, Saada-Bouzid, and Ferrara et al. definitions respectively. The incidence of hyperprogression increased when new lesions were included in the definition. The incidence rate with modified Champiat, Saada-Bouzid and Ferrara et al. definitions were 11% (N=16), 15% (N=21) and 6% (N=9) respectively (table 1). Incorporating new lesions enabled the detection of more HPD cases, and the change in the sum of lesions are depicted in figure 1. The difference in incidence between original and modified definitions was statistically significant only for the Champiat et al. (X2= 3.0, p=0.05).

Conclusions Incorporation of new lesions in the definition of hyperprogression resulted in an increase in HPD incidence for all three definitions. However, statistically significant difference was observed only for the Champiat et al. definition. There are limitations of utilizing RECIST 1.1 in the identification of HPD as it does not take new lesions into consideration. This study highlights the importance of including new lesions when defining HPD to accurately capture HPD.


  1. Park HJ, Kim KW, Won SE, Yoon S, Chae YK, Tirumani SH, et al. Definition, incidence, and challenges for assessment of hyperprogressive disease during cancer treatment with immune checkpoint inhibitors: a systematic review and meta-analysis. JAMA Netw Open 2021 Mar 1;4(3):e211136.

  2. Frelaut M, Le Tourneau C, Borcoman E. Hyperprogression under Immunotherapy. Int J Mol Sci. 2019 May 30;20(11):2674.

  3. Sabio E, Chan TA. The good, the bad, and the ugly: hyperprogression in cancer patients following immune checkpoint therapy. Genome Med. 2019 Jul 24;11(1):43.

  4. Champiat S, Besse B, Marabelle A. Hyperprogression during immunotherapy: do we really want to know? Ann Oncol. 2019 Jul 1;30(7):1028–31.

  5. Champiat S, Dercle L, Ammari S, Massard C, Hollebecque A, Postel-Vinay S, et al. Hyperprogressive Disease Is a New Pattern of Progression in Cancer Patients Treated by Anti-PD-1/PD-L1. Clin Cancer Res Off J Am Assoc Cancer Res. 2017 Apr 15;23(8):1920–8.

  6. Saâda-Bouzid E, Defaucheux C, Karabajakian A, Coloma VP, Servois V, Paoletti X, et al. Hyperprogression during anti-PD-1/PD-L1 therapy in patients with recurrent and/or metastatic head and neck squamous cell carcinoma. Ann Oncol Off J Eur Soc Med Oncol. 2017 Jul 1;28(7):1605–11.

  7. Ferrara R, Mezquita L, Texier M, Lahmar J, Audigier-Valette C, Tessonnier L, et al. Hyperprogressive disease in patients with advanced non–small cell lung cancer treated With PD-1/PD-L1 inhibitors or with single-agent chemotherapy. JAMA Oncol 2018 Nov;4(11):1543–52.

Ethics Approval The study was approved by Northwestern University’s Institutional Review Board, study number STU00207117.

Abstract 1407 Figure 1

The changes of sum of lesions depending on patients with hyperprogression according to different definitions of hyperprogression and modification.

Abstract 1407 Table 1

A summary of the incidence of hyperprogression according to main different definitions of hyperprogression and modified definitions

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