Asia Oceania Journal of Nuclear Medicine and Biology

Asia Oceania Journal of Nuclear Medicine and Biology

Complex Immunotherapy-mediated Response Patterns Depicted on Serial 18F-FDG PET imaging of Hodgkin Lymphoma Patient Undergoing Pembrolizumab Therapy

Document Type : Case report

Authors
Mohanad Badarneh 1
Ahmed Saad Abdlkadir 1
Mohammad Makoseh 2
Alaa Abufara 2
Akram Al-Ibraheem 1, 3
1 Department of Nuclear Medicine, King Hussein Cancer Center (KHCC), Amman, Jordan
2 Department of Medicine, King Hussein Cancer Center (KHCC), Amman, Jordan
3 School of Medicine, The University of Jordan, Amman, Jordan
10.22038/aojnmb.2025.86889.1621
Abstract
Over the past decade, the role of 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in assessing treatment response for lymphoma patients undergoing immunotherapy has been extensively investigated. The advent of immunotherapy has challenged the utility of the established Lugano criteria, prompting the development of novel immunotherapy-specific response criteria now employed in clinical practice. Following 18F-FDG PET/CT evaluation after up to eight immunotherapy cycles, patients are typically transitioned to conventional imaging modalities if immunotherapy continuation is warranted. This case report illustrates the application of serial 18F-FDG PET/CT in monitoring a 67-year-old patient with Hodgkin lymphoma receiving immunotherapy, revealing complex, atypical response patterns unresolved by existing criteria. Notably, two episodes of pseudoprogression occurred at two distinct time points, one during cycle 5 and the other during cycle 22. Furthermore, an immunotherapy-enhanced abscopal effect was seen during radio-immunotherapy, leading to short-term disease remission. Our findings suggest that 18F-FDG PET/CT provides superior predictive value in delineating heterogeneous response patterns, thereby informing critical decisions regarding immunotherapy cessation or adjunctive therapeutic interventions.
Keywords
PET/CT
18F-FDG
Immunotherapy
Abscopal Effect
Pseudoprogression
Subjects
  1. Unterrainer M, Ruzicka M, Fabritius MP, Mittlmeier LM, Winkelmann M, Rübenthaler J, et al. PET/CT imaging for tumour response assessment to immunotherapy: current status and future directions. European Radiology Experimental. 2020; 4(1): 63.
  2. Shanbhag S, Ambinder RF. Hodgkin lymphoma: A review and update on recent progress. CA: A Cancer Journal for Clinicians. 2018; 68(2): 116-32.
  3. Al-Ibraheem A, Abdlkadir AS, Juweid ME, Al-Rabi K, Ma’koseh M, Abdel-Razeq H, Mansour A. FDG-PET/CT in the monitoring of lymphoma immunotherapy response: current status and future prospects. Cancers. 2023; 15(4): 1063.
  4. Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: The lugano classification. Journal of Clinical Oncology. 2014; 32(27): 3059-67.
  5. Skusa C, Weber M-A, Böttcher S, Thierfelder KM. Criteria-based imaging and response evaluation of lymphoma 20 Years after cheson: What is new? Rofo. 2020; 192(7): 657-668.
  6. Younes A, Hilden P, Coiffier B, Hagenbeek A, Salles G, Wilson W, et al. International working group consensus response evaluation criteria in lymphoma (RECIL 2017). Annals of Oncology. 2017; 28(7): 1436-47.
  7. Tan AC, Emmett L, Lo S, Liu V, Kapoor R, Carlino MS, et al. FDG-PET response and outcome from anti-PD-1 therapy in metastatic melanoma. Annals of Oncology. 2018; 29(10): 2115-20.
  8. Amrane K, Le Meur C, Thuillier P, Dzuko Kamga J, Alemany P, Chauvelot F, et al. Case Report: Long-term metabolic response of metastatic uveal melanoma to pembrolizumab on FDG-PET/CT despite a serial pseudo-progressions phenomenon. Frontiers in Immunology. 2023; 14: 1243208.
  9. Dercle L, Seban R-D, Lazarovici J, Schwartz LH, Houot R, Ammari S, et al. 18F-FDG PET and CT scans detect new imaging patterns of response and progression in patients with Hodgkin lymphoma treated by anti-programmed death 1 immune checkpoint inhibitor. Journal of Nuclear Medicine. 2018; 59(1):15-24.
  10. Cheah CY, Fowler NH, Neelapu SS. Targeting the programmed death-1/programmed death-ligand 1 axis in lymphoma. Current Opinion in Oncology. 2015; 27(5): 384-91.
  11. Al-Ibraheem A, Mottaghy FM, Juweid ME. PET/CT in Hodgkin lymphoma: An update. Seminars in Nuclear Medicine. 2023; 53(3): 303-19.
  12. Cheson BD. Rethinking clinical response and outcome assessment in a biologic age. Current Oncology Reports. 2015; 17(6):27.
  13. Strati P, Spiotto MT. Incorporating immunotherapy with radiotherapy for lymphomas. Lymphatics. 2023; 1(3):273-86.
  14. Janopaul-Naylor JR, Shen Y, Qian DC, Buchwald ZS. The Abscopal effect: A review of pre-clinical and clinical advances. International Journal of Molecular Sciences. 2021; 22(20): 11061.
  15. Lee AJ, Kim KW, Cho YC, Ko Y, Sung YS, Shin Y, et al. Incidence of immune-mediated pseudoprogression of lymphoma treated with immune checkpoint inhibitors: Systematic review and meta-analysis. Journal of Clinical Medicine. 2021; 10(11): 2257.
  16. Bajwa R, Cheema A, Khan T, Amirpour A, Paul A, Chaughtai S, et al. Adverse effects of immune checkpoint inhibitors (programmed death-1 inhibitors and cytotoxic T-lymphocyte-associated protein-4 inhibitors): Results of a retrospective study. J Clin Med Res. 2019; 11(4): 225-36.
  17. Al-Ibraheem A, Abdlkadir AS, Lopci E, Allouzi S, Paez D, Alkuwari M, et al. FDG-PET in chimeric antigen receptor T-Cell (CAR T-Cell) therapy toxicity: A systematic review. Cancers. 2024; 16(9): 1728.
Asia Oceania Journal of Nuclear Medicine and Biology
Volume 13, Issue 2
July 2025
Pages 185-189