Redefining Clinical Hyperprogression: The Incidence, Clinical Implications, and Risk Factors of Hyperprogression in Non-Small Cell Lung Cancer Treated with Immunotherapy

Trie Arni Djunadi; Youjin Oh; Jeeyeon Lee; Jisang Yu; Liam Il-Young Chung; Yeunho Lee; Leeseul Kim; Timothy Hong; Soowon Lee; Zunairah Shah; Joo Hee Park; Sung Mi Yoon; Young Kwang Chae

doi:10.1016/j.cllc.2024.03.001

Redefining Clinical Hyperprogression: The Incidence, Clinical Implications, and Risk Factors of Hyperprogression in Non-Small Cell Lung Cancer Treated with Immunotherapy

Clin Lung Cancer. 2024 Mar 16:S1525-7304(24)00036-6. doi: 10.1016/j.cllc.2024.03.001. Online ahead of print.

Authors

Trie Arni Djunadi¹, Youjin Oh², Jeeyeon Lee³, Jisang Yu⁴, Liam Il-Young Chung⁴, Yeunho Lee⁵, Leeseul Kim⁶, Timothy Hong⁷, Soowon Lee⁸, Zunairah Shah⁹, Joo Hee Park⁴, Sung Mi Yoon¹⁰, Young Kwang Chae¹¹

Affiliations

¹ Feinberg School of Medicine, Northwestern University, Chicago, IL; Department of Internal Medicine, Richmond University Medical Centre, Staten Island, NY.
² Feinberg School of Medicine, Northwestern University, Chicago, IL; Department of Internal Medicine, John H. Stroger, Jr. Hospital of Cook County, Chicago, IL.
³ Feinberg School of Medicine, Northwestern University, Chicago, IL; School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
⁴ Feinberg School of Medicine, Northwestern University, Chicago, IL.
⁵ Department of Pediatrics, University of Hawai'i, Honolulu, HI.
⁶ Department of Internal Medicine, Ascension Saint Francis Hospital, Evanston, IL.
⁷ Northwestern University, Evanston, IL.
⁸ Baylor University, Waco, TX.
⁹ Department of Hematology Oncology, Roswell Park Comprehensive Care Center, Buffalo, NY.
¹⁰ Department of Internal Medicine, Jacobi Medical Center/North Central Bronx Hospital Albert Einstein College of Medicine, Bronx, NY.
¹¹ Feinberg School of Medicine, Northwestern University, Chicago, IL. Electronic address: YCHAE@nm.org.

PMID: 38644088
DOI: 10.1016/j.cllc.2024.03.001

Abstract

Introduction: Immune checkpoint inhibitors (ICIs) may be associated with hyperprogressive disease (HPD). However, there is currently no standardized definition of HPD, with its risk factors and clinical implications remaining unclear. We investigated HPD in lung cancer patients undergoing immunotherapy, aiming to redefine HPD, identify risk factors, and assess its impact on survival.

Methods: Clinical and radiologic data from 121 non-small cell lung cancer (NSCLC) patients with 136 immunotherapy cases were reviewed retrospectively. Three HPD definitions (Champiat et al., HPDc; Saâda-Bouzid et al., HPDs; and Ferrara et al., HPDf) were employed. Additionally, all new measurable lesions on the post-treatment CT scan were incorporated in measuring the sum of longest diameters (SLD) to define modified HPD (mHPD).

Results: Among the 121 patients, 4 (3.3%) had HPDc, 11 (9.1%) had HPDs, and none had HPDf. Adding all new measurable lesions increased HPD incidence by 5%-10% across definitions. Multivariate analysis revealed significantly lower progression-free survival (PFS) and overall survival (OS) for patients with HPDc (HR 5.25, P = .001; HR 3.75, P = .015) and HPDs (HR 3.74, P < .001; HR 3.46, P < .001) compared to those without. Patients with mHPD showed similarly poor survival outcomes as HPD patients. Liver metastasis at diagnosis was associated with HPDs, and a high tumor burden correlated with HPDc.

Conclusions: The incidence and risk factors of HPD varied with different definitions, but mHPD identified more cases with poor outcomes. This comprehensive approach may enhance the identification of at-risk patients and lead to a better understanding of HPD in lung cancer during immunotherapy.

Keywords: Disease progression; Immunology; Prognosis; Respiratory tract tumors; Retrospective studies.