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.

Key words

Hyperprogression after immunotehrapy - hyperprogression with check point inhibitors - immunotherapy linked to hyperprogression

Publikationsverlauf

Artikel online veröffentlicht:
14. Dezember 2020

• References

• 1 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 2017;23:1920-8.
• 2 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 2017;28:1605-11.
• 3 Kato S, Goodman A, Walavalkar V, Barkauskas DA, Sharabi A, Kurzrock R, et al. Hyperprogressors after immunotherapy: Analysis of genomic alterations associated with accelerated growth rate. Clin Cancer Res 2017;23:4242-50.
• 4 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;4:1543-52.
• 5 Strannegård Ö, Thorén FB. Opposing effects of immunotherapy in melanoma using multisubtype interferon-alpha-can tumor immune escape after immunotherapy accelerate disease progression? Oncoimmunology 2016;5:e1091147.
• 6 Mellema WW, Burgers SA, Smit EF. Tumor flare after start of RAF inhibition in KRAS mutated NSCLC: A case report. Lung Cancer 2015;87:201-3.
• 7 Kuriyama Y, Kim YH, Nagai H, Ozasa H, Sakamori Y, Mishima M, et al. Disease flare after discontinuation of crizotinib in anaplastic lymphoma kinase-positive lung cancer. Case Rep Oncol 2013;6:430-3.
• 8 Kleffel S, Posch C, Barthel SR, Mueller H, Schlapbach C, Guenova E, et al. Melanoma cell-intrinsic PD-1 receptor functions promote tumor growth. Cell 2015;162:1242-56.
• 9 Francisco LM, Sage PT, Sharpe AH. The PD-1 pathway in tolerance and autoimmunity. Immunol Rev 2010;236:219-42.
• 10 Koyama S, Akbay EA, Li YY, Herter-Sprie GS, Buczkowski KA, Richards WG, et al. Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints. Nat Commun 2016;7:10501.