Optimizing frontline therapy for classical Hodgkin lymphoma: A mini-review of PET-directed chemotherapy, brentuximab-based regimens, and checkpoint inhibitor combinations
Classical Hodgkin lymphoma is a highly curable malignancy, but long-term treatment-related toxicities remain a challenge, especially in young survivors. In recent years, treatment has shifted from traditional doxorubicin, bleomycin, vinblastine, and dacarbazine regimens to novel approaches such as positron emission tomography-guided therapy, brentuximab vedotin-doxorubicin, vinblastine, dacarbazine (AVD), and checkpoint inhibitor combinations such as nivolumab (Nivo)-AVD. This review evaluates these three frontline strategies in terms of efficacy, toxicity, and their potential to personalize treatment and minimize late complications. Drawing from trials such as ECHELON-1, NIVAHL, SWOG S1826, and BREACH, we analyze current evidence, evaluate conflicting data, and propose considerations for tailoring therapy to patient subgroups.
- Ansell SM, Radford J, Connors JM, et al. Overall survival and safety with nivolumab for relapsed/refractory classic Hodgkin lymphoma: Final results of a phase II study. J Clin Oncol. 2021;39(20):2129-2137. doi: 10.1200/JCO.20.03184
- Shanbhag S, Ambinder RF. Hodgkin lymphoma: A review and update on recent progress. CA Cancer J Clin. 2018;68(2):116-132. doi: 10.3322/caac.21438
- Eichenauer DA, Engert A, Plütschow A, et al. Ivolumab and AVD for early-stage unfavorable Hodgkin lymphoma: Final analysis of the German Hodgkin study group NIVAHL trial. J Clin Oncol. 2021;39(17):1895-1904. doi: 10.1200/JCO.20.03264
- Radford J, Illidge T, Counsell N, et al. Results of a trial of PET-directed therapy for early-stage Hodgkin’s lymphoma. New Engl J Med. 2015;373(3):245-253. doi: 10.1056/NEJMoa1500896
- SEER Cancer Statistics (N.D.). National Cancer Institute. Available from: https://seer.cancer.gov [Last accessed on 2025 Jan 05].
- Ng AK, Van Leeuwen FE, Hodgson DC, Constine LS, Travis LB, Aleman BM. Long-term complications of treatment in adults with Hodgkin lymphoma. Blood. 2020;136(24):2731-2739. doi: 10.1182/blood.2020006067
- Sasse S, Rothe A, Goergen H, et al. Long-term adverse effects in Hodgkin lymphoma survivors: A systematic review. HemaSphere. 2022;6(5):e734. doi: 10.1097/HS9.0000000000000734
- Connors JM, Jurczak W, Straus DJ, et al. Brentuximab vedotin with chemotherapy for stage III or IV Hodgkin’s lymphoma. New Engl J Med. 2018;378(4):331-344. doi: 10.1056/NEJMoa1708984
- Younes A, Connors JM, Park SI, et al. Brentuximab vedotin combined with AVD for newly diagnosed stage III or IV classical Hodgkin lymphoma: Final results of a phase 3 trial (ECHELON-1). Blood. 2017;130(Suppl 1):LBA6. doi: 10.1182/blood.V130.Suppl_1.LBA-6.LBA-6
- Zinzani PL, Younes A, Carlo-Stella C, et al. Nivolumab for relapsed/refractory classic Hodgkin lymphoma after failure of autologous hematopoietic cell transplantation: Extended follow-up of the multicohort single-arm phase II CheckMate 205 trial. Blood. 2019;133(4):270-280. doi: 10.1182/blood-2018-07-861456
- Diefenbach CS, Hong F, David KA, et al. Nivolumab-AVD versus brentuximab vedotin-AVD for advanced-stage Hodgkin lymphoma. New Engl J Med. 2023;388(5):399-409. doi: 10.1056/NEJMoa2214085
- Behringer K, Goergen H, Kobe C, et al. APET-guided response-adapted treatment in advanced-stage Hodgkin lymphoma (HD21 trial): A randomized open-label phase 3 study of the German Hodgkin study group. J Clin Oncol. 2020;38(15-suppl):8000. doi: 10.1200/JCO.2020.38.15-suppl.8000
- Engert A, Haverkamp H, Kobe C, et al. Reduced treatment intensity in patients with early-stage Hodgkin’s lymphoma. New Engl J Med. 2010;363(7):640-652. doi: 10.1056/NEJMoa1000067
- Borchmann P, Haverkamp H, Diehl V, et al. Eight cycles of escalated-dose BEACOPP compared with four cycles of escalated-dose BEACOPP followed by four cycles of baseline-dose BEACOPP: Final analysis of the HD12 trial of the German Hodgkin study group. J Clin Oncol. 2011;29(35):4497-4503. doi: 10.1200/JCO.2010.33.9549
- Johnson P, Federico M, Kirkwood A, et al. Adapted treatment guided by interim PET-CT scan in advanced Hodgkin’s lymphoma. New Engl J Med. 2016;374(25):2419-2429. doi: 10.1056/NEJMoa1510070