Generational shift of the treatment of classical Hodgkin lymphoma

Czech version

Authors: A. Sýkorová ¹; H. Móciková ²; V. Procházka ³
Authors‘ workplace: IV. interní hematologická klinika LF UK a FN Hradec Králové ¹; Hematologická klinika 3. LF UK a FNKV, Praha ²; Hemato-onkologická klinika LF UP a FN Olomouc ³
Published in: Transfuze Hematol. dnes,31, 2025, No. 4, p. 253-268.
Category: Review/Educational Papers
doi: https://doi.org/10.48095/cctahd202521

Overview

Classical Hodgkin lymphoma (cHL) has long been regarded as a model of success in modern haemato-oncology, particularly among patients younger than 60 years, where contemporary treatment strategies achieve cure rates of approximately 80–90%, depending on clinical stage. These excellent outcomes are the result of decades of clinical research and the development of highly effective chemo-radiotherapy treatments. However, significant challenges remain, including acute and late treatment-related toxicities, as well as the limited therapeutic options for older patients and those with relapsed or refractory (R/R) disease. Consequently, cHL continues to represent an evolving therapeutic landscape, with ongoing efforts focused on optimizing the balance between efficacy and long-term tolerability. In recent years, the field has undergone a paradigm shift with the advent of targeted agents and immunotherapy. Notably, the introduction of the antibody–drug conjugate brentuximab vedotin and immune checkpoint inhibitors (nivolumab, pembrolizumab) have reshaped treatment algorithms. Initially reserved for use in later lines of therapy, these agents are now being incorporated increasingly into first -⁠ and second-line of treatment. This evolution offers not only the perspective of improved efficacy in older patients and those with R/R disease, but also the potential to mitigate toxicity and enhance quality of life in younger patients. This review provides an overview of the latest evidence on integrating these novel approaches into frontline and second-line treatment of cHL. It also highlights their implications for clinical practice, with particular attention to the evolving therapeutic paradigm and the growing role of personalized medicine within the Czech healthcare context.

Keywords:

Prognosis – treatment – classical Hodgkin lymphoma – novel agents

Sources

1. Alaggio R, Amador C, Anagnostopoulos I, et al. The 5th edition of the World Health Organization classification of haematolymphoid tumours: lymphoid neoplasms. Leukemia. 2022; 36 (7): 1720–1748. doi: 10.1038/s41375 -⁠ 022-01620-2.

2. Glaser SL, Jarrett RF. The epidemiology of Hodgkin’s disease. Baillieres Clin Haematol. 1996; 9 (3): 401–416. doi: 10.1016/s0950-3536 (96) 80018-7.

3. Franceschi S, Dal Maso L, La Vecchia C. Advances in the epidemiology of HIV-associated non-Hodgkin’s lymphoma and other lymphoid neoplasms. Int J Cancer. 1999; 83 (4): 481–485. doi: 10.1002/ (sici) 1097-0215 (19991112) 83 : 4<481:: aid-ijc8>3.0.co; 2-5.

4. Küppers R. The biology of Hodgkin’s lymphoma. Nat Rev Cancer. 2009; 9 (1): 15–27. doi: 10.1038/nrc2542.

5. https: //www.uzis.cz/res/f/008447/novotvary2019-2021.pdf.

6. Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014; 32 (27): 3059–3068. doi: 10.1200/JCO.2013.54.8800.

7. Zwarthoed C, El-Galaly TC, Canepari M, et al. Prognostic value of bone marrow tracer uptake pattern in baseline PET scans in Hodgkin lymphoma: results from an international collaborative study. J Nucl Med. 2017; 58 (8): 1249–1254. doi: 10.2967/jnumed.116.184218.

8. Diehl V, Stein H, Hummel M, Zollinger R, Connors JM. Hodgkin’s lymphoma: biology and treatment strategies for primary, refractory, and relapsed disease. Hematol Am Soc Hematol Educ Program. Published online 2003 : 225–247. doi: 10.1182/asheducation-2003.1.225.

9. Hasenclever D, Diehl V. A prognostic score for advanced Hodgkin’s disease. International Prognostic Factors Project on Advanced Hodgkin’s Disease. N Engl J Med. 1998; 339 (21): 1506–1514. doi: 10.1056/NEJM199811193392104.

10. Maco M, Kupcova K, Herman V, et al. Circulating tumor DNA in Hodgkin lymphoma. Ann Hematol. 2022; 101 (11): 2393–2403. doi: 10.1007/s00277-022-04949-x.

11. Spina V, Bruscaggin A, Cuccaro A, et al. Circulating tumor DNA reveals genetics, clonal evolution, and residual disease in classical Hodgkin lymphoma. Blood. 2018; 131 (22): 2413–2425. doi: 10.1182/blood-2017-11-812073.

12. Procházka V, Gawande RS, Cayci Z, et al. Positron emission tomography-based assessment of metabolic tumor volume predicts survival after autologous hematopoietic cell transplantation for Hodgkin lymphoma. Biol Blood Marrow Transplant. 2018; 24 (1): 64–70. doi: 10.1016/j.bbmt.2017.09.006.

13. Kanoun S, Rossi C, Berriolo-Riedinger A, et al. Baseline metabolic tumour volume is an independent prognostic factor in Hodgkin lymphoma. Eur J Nucl Med Mol Imaging. 2014; 41 (9): 1735–1743. doi: 10.1007/s002 59-014-2783-x.

14. Cottereau AS, Versari A, Loft A, et al. Prognostic value of baseline metabolic tumor volume in early-stage Hodgkin lymphoma in the standard arm of the H10 trial. Blood. 2018; 131 (13): 1456–1463. doi: 10.1182/blood -⁠ 2017-07-795476.

15. Rossi C, André M, Dupuis J, et al. High-risk stage IIB Hodgkin lymphoma treated in the H10 and AHL2011 trials: TMTV is a useful risk factor to stratify patients at baseline. Haematologica. 2022; 107 (12). doi: 10.3324/ haematol.2021.280004.

16. Kredátusová A, Procházka V, Papajík T. Voľná nádorová DNA u pacientov s klasickým Hodgkinovým lymfómom. Transfuze Hematol Dnes. 2022; 28 (3): 135–142. doi: 10.48095/cctahd2022prolekare.cz9.

17. Procházka V, Móciková H, Sýkorová A. Predictive role of the Hodgkin lymphoma-associated cytokines: a prospective study of the Czech Hodgkin Study Group. Hemasphere. 2022; 3 (6 Suppl): 21. doi: 10.1097/01.HS9.0000890756.00821.02.

18. Sauer M, Plütschow A, Jachimowicz RD, et al. Baseline serum TARC levels predict therapy outcome in patients with Hodgkin lymphoma. Am J Hematol. 2013; 88 (2): 113–115. doi: 10.1002/ajh.23361.

19. Guidetti A, Mazzocchi A, Miceli R, et al. Early reduction of serum TARC levels may predict for success of ABVD as frontline treatment in patients with Hodgkin Lymphoma. Leuk Res. 2017; 62 : 91–97. doi: 10.1016/ j.leukres.2017.09.018.

20. Engert A, Diehl V, Franklin J, et al. Escalated-dose BEACOPP in the treatment of patients with advanced-stage Hodgkin’s lymphoma: 10 years of follow-up of the GHSG HD9 study. J Clin Oncol. 2009; 27 (27): 4548–4554. doi: 10.1200/JCO.2008.19.8820.

21. 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 with or without radiotherapy in patients with advanced-stage hodgkin’s lymphoma: final analysis of the HD12 trial of the German Hodgkin Study Group. J Clin Oncol. 2011; 29 (32): 4234–4242. doi: 10.1200/JCO.2010. 33.9549.

22. Engert A, Haverkamp H, Kobe C, et al. Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin’s lymphoma (HD15 trial): a randomised, open-label, phase 3 non-inferiority trial. The Lancet. 2012; 379 (9828): 1791–1799. doi: 10.1016/S0140-6736 (11) 61940-5.

23. Borchmann P, Goergen H, Kobe C, et al. PET-guided treatment in patients with advanced-stage Hodgkin’s lymphoma (HD18): final results of an open-label, international, randomised phase 3 trial by the German Hodgkin Study Group. Lancet. 2017; 390 (10114): 2790–2802. doi: 10.1016/S0140-6736 (17) 32134-7.

24. Sasse S, Bröckelmann PJ, Goergen H, et al. Long-term follow-up of contemporary treatment in early-stage Hodgkin lymphoma: updated analyses of the German Hodgkin Study Group HD7, HD8, HD10, and HD11 trials. J Clin Oncol. 2017; 35 (18): 1999–2007. doi: 10.1200/ JCO.2016.70.9410.

25. Kreissl S, Goergen H, Buehnen I, et al. PET-guided eBEACOPP treatment of advanced-stage Hodgkin lymphoma (HD18): follow-up analysis of an international, open-label, randomised, phase 3 trial. Lancet Haematol. 2021; 8 (6): e398–e409. doi: 10.1016/S2352-3026 (21) 00101-0.

26. Borchmann P, Ferdinandus J, Schneider G, et al. Assessing the efficacy and tolerability of PET-guided BrECADD versus eBEACOPP in advanced-stage, classical Hodgkin lymphoma (HD21): a randomised, multicentre, parallel, open-label, phase 3 trial. Lancet. 2024; 404 (10450): 341–352. doi: 10.1016/S0140-6736 (24) 01315-1.

27. Shbib Dabaja B, Boyce-Fappiano D, Dong W, et al. Second malignancies in patients with Hodgkin’s Lymphoma: Half a century of experience. Clin Transl Radiat Oncol. 2022; 35 : 64–69. doi: 10.1016/j.ctro.2022.04.011.

28. van Leeuwen FE, Ng AK. Late sequelae in Hodgkin lymphoma survivors. Hematol Oncol. 2017; 35 (Suppl 1): 60–66. doi: 10.1002/hon.2402.

29. André MPE, Carde P, Viviani S, et al. Long-term overall survival and toxicities of ABVD vs BEACOPP in advanced Hodgkin lymphoma: A pooled analysis of four randomized trials. Cancer Med. 2020; 9 (18): 6565–6575. doi: 10.1002/cam4.3298.

30. Kerckhove N, Collin A, Condé S, Chaleteix C, Pezet D, Balayssac D. Long-term effects, pathophysiological mechanisms, and risk factors of chemotherapy-induced peripheral neuropathies: a comprehensive literature review. Front Pharmacol. 2017; 8 : 86. doi: 10.3389/fphar.2017.00086.

31. Lu Z, Teng Y, Ning X, Wang H, Feng W, Ou C. Long-term risk of cardiovascular disease mortality among classic Hodgkin lymphoma survivors. Cancer. 2022; 128 (18): 3330–3339. doi: 10.1002/cncr.34375.

32. Behringer K, Mueller H, Goergen H, et al. Gonadal function and fertility in survivors after Hodgkin lymphoma treatment within the German Hodgkin Study Group HD13 to HD15 trials. J Clin Oncol. 2013; 31 (2): 231–239. doi: 10.1200/JCO.2012.44.3721.

33. Macklin-Doherty A, Jones M, Coulson P, et al. Risk of thyroid disorders in adult and childhood Hodgkin lymphoma survivors 40 years after treatment. Leuk Lymphoma. 2022; 63 (3): 562–572. doi: 10.1080/10428194.2021.1999445.

34. Evens AM, Helenowski I, Ramsdale E, et al. A retrospective multicenter analysis of elderly Hodgkin lymphoma: outcomes and prognostic factors in the modern era. Blood. 2012; 119 (3): 692–695. doi: 10.1182/blood-2011-09-378414.

35. Böll B, Goergen H, Behringer K, et al. Bleomycin in older early-stage favorable Hodgkin lymphoma patients: analysis of the German Hodgkin Study Group (GHSG) HD10 and HD13 trials. Blood. 2016; 127 (18): 2189–2192. doi: 10.1182/blood-2015-11-681064.

36. Fuchs M, Jacob AS, Kaul H, et al. Follow-up of the GHSG HD16 trial of PET-guided treatment in early-stage favorable Hodgkin lymphoma. Leukemia. 2024; 38 (1): 160–167. doi: 10.1038/s41375-023-02064-y.

37. Borchmann P, Plütschow A, Kobe C, et al. PET-guided omission of radiotherapy in early-stage unfavourable Hodgkin lymphoma (GHSG HD17): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2021; 22 (2): 223–234. doi: 10.1016/S1470-2045 (20) 30601-X.

38. Barrett A, Collins GP. Older patients with Hodgkin Lymphoma: Walking the tightrope of efficacy and toxicity. Front Oncol. 2022; 12 : 1017787. doi: 10.3389/fonc.2022.1017787.

39. Evens AM, Sweetenham JW, Horning SJ. Hodgkin lymphoma in older patients: an uncommon disease in need of study. Oncol Williston Park N. 2008; 22 (12): 1369–1379.

40. Engert A, Ballova V, Haverkamp H, et al. Hodgkin’s lymphoma in elderly patients: a comprehensive retrospective analysis from the German Hodgkin’s Study Group. J Clin Oncol. 2005; 23 (22): 5052–5060. doi: 10.1200/ JCO.2005.11.080.

41. Sykorova A, Mocikova H, Lukasova M, et al. Outcome of elderly patients with classical Hodgkin’s lymphoma. Leuk Res. 2020; 90 : 106311. doi: 10.1016/j.leukres.2020.106311.

42. Ansell SM, Lesokhin AM, Borrello I, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med. 2015; 372 (4): 311–319. doi: 10.1056/NEJMoa 1411087.

43. Armand P, Engert A, Younes A, 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. J Clin Oncol. 2018; 36 (14): 1428–1439. doi: 10.1200/JCO.2017.76.0793.

44. Younes A, Gopal AK, Smith SE, et al. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin’s lymphoma. J Clin Oncol. 2012; 30 (18): 2183–2189. doi: 10.1200/JCO.2011.38.0410.

45. Bröckelmann PJ, Goergen H, Keller U, et al. Efficacy of nivolumab and AVD in early-stage unfavorable classic Hodgkin lymphoma: the randomized phase 2 German Hodgkin Study Group NIVAHL trial. JAMA Oncol. 2020; 6 (6): 872–880. doi: 10.1001/jamaoncol.2020.0750.

46. Herrera AF, LeBlanc M, Castellino SM, et al. Nivolumab+AVD in advanced-stage Classic Hodgkin’s lymphoma. N Engl J Med. 2024; 391 (15): 1379–1389. doi: 10.1056/NEJMoa 2405888.

47. Bröckelmann PJ, Bühnen I, Meissner J, et al. Nivolumab and doxorubicin, vinblastine, and dacarbazine in early-stage unfavorable Hodgkin lymphoma: final analysis of the randomized German Hodgkin Study Group phase II NIVAHL trial. J Clin Oncol. 2023; 41 (6): 1193–1199. doi: 10.1200/JCO.22.02355.

48. Behringer K, Goergen H, Hitz F, et al. Omission of dacarbazine or bleomycin, or both, from the ABVD regimen in treatment of early-stage favourable Hodgkin’s lymphoma (GHSG HD13): an open-label, randomised, non-inferiority trial. Lancet. 2015; 385 (9976): 1418–1427. doi: 10.1016/S0140-6736 (14) 61469-0.

49. Fuchs M, Goergen H, Kobe C, et al. PET-guided treatment of early-stage favorable Hodgkin lymphoma: final results of the international, randomized phase 3 trial HD16 by the German Hodgkin Study Group. Blood. 2018; 132 (Suppl 1): 925–925. doi: 10.1182/blood-2018-99 -⁠ 114519.

50. André MPE, Girinsky T, Federico M, et al. Early positron emission tomography response-adapted treatment in stage I and II Hodgkin lymphoma: final results of the randomized EORTC/LYSA/FIL H10 trial. J Clin Oncol. 2017; 35 (16): 1786–1794. doi: 10.1200/JCO.2016.68.6394.

51. Radford J, Illidge T, Counsell N, et al. Results of a trial of PET-directed therapy for early-stage Hodgkin’s lymphoma. N Engl J Med. 2015; 372 (17): 1598–1607. doi: 10.1056/ NEJMoa1408648.

52. Eich HT, Diehl V, Görgen H, et al. Intensified chemotherapy and dose-reduced involved-field radiotherapy in patients with early unfavorable Hodgkin’s lymphoma: final analysis of the German Hodgkin Study Group HD11 trial. J Clin Oncol. 2010; 28 (27): 4199–4206. doi: 10.1200/JCO.2010.29.8018.

53. von Tresckow B, Plütschow A, Fuchs M, et al. Dose-intensification in early unfavorable Hodgkin’s lymphoma: final analysis of the German Hodgkin Study Group HD14 trial. J Clin Oncol. 2012; 30 (9): 907–913. doi: 10.1200/ JCO.2011.38.5807.

54. Gillessen S, Plütschow A, Fuchs M, et al. Intensified treatment of patients with early stage, unfavourable Hodgkin lymphoma: long-term follow-up of a randomised, international phase 3 trial of the German Hodgkin Study Group (GHSG HD14). Lancet Haematol. 2021; 8 (4): e278–e288. doi: 10.1016/S2352-3026 (21) 00029-6.

55. Lee HJ, Abramson JS, Bartlett NL, et al. Brentuximab vedotin, nivolumab, doxorubicin, and dacarbazine (AN+AD) for early stage classic Hodgkin lymphoma: interim efficacy and safety results from the single-arm phase 2 study (SGN35-027 Part C). Blood. 2022; 140 (Suppl 1): 9399–9401. doi: 10.1182/blood-2022-156576.

56. Radford, J, Adedayo, T, Ardavan, A. RADAR: An international phase III, PET response-adapted, randomised trial in progress, comparing ABVD±ISRT with brentuximab vedotin+AVD±ISRT in patients with previously untreated limited-stage classical Hodgkin lymphoma. Hemasphere. 2022; 6 (25): 12–13. doi: 10.1097/01.HS9.0000890668.27643.97.

57. Henderson TO, Hu B, Keller F, et al. AHOD2131: A randomized phase 3 response-adapted trial comparing standard therapy with immuno-oncology therapy for children and adults with newly diagnosed stage I and II classic Hodgkin lymphoma. Blood. 2023; 142 (Suppl 1): 3084–3084. doi: 10.1182/blood-2023-189652.

58. Abramson JS, Arnason JE, LaCasce AS, et al. Brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine for nonbulky limited-stage classical Hodgkin lymphoma. Blood. 2019; 134 (7): 606–613. doi: 10.1182/blood.2019001272.

59. Abramson JS, Bengston E, Redd R, et al. Brentuximab vedotin plus doxorubicin and dacarbazine in nonbulky limited-stage classical Hodgkin lymphoma. Blood Adv. 2023; 7 (7): 1130–1136. doi: 10.1182/bloodadvances.2022008420.

60. Kumar A, Casulo C, Advani RH, et al. Brentuximab vedotin combined with chemotherapy in patients with newly diagnosed early-stage, unfavorable-risk Hodgkin lymphoma. J Clin Oncol. 2021; 39 (20): 2257–2265. doi: 10.1200/JCO.21.00108.

61. Lynch RC, Ujjani CS, Poh C, et al. Concurrent pembrolizumab with AVD for untreated classic Hodgkin lymphoma. Blood. 2023; 141 (21): 2576–2586. doi: 10.1182/blood. 2022019254.

62. Allen PB, Savas H, Evens AM, et al. Pembrolizumab followed by AVD in untreated early unfavorable and advanced-stage classical Hodgkin lymphoma. Blood. 2021; 137 (10): 1318–1326. doi: 10.1182/blood.2020007400.

63. Bröckelmann P, Kaul H, Fuchs M. Trial in progress: individualized immunotherapy in early-stage unfavorable Hodgkin lymphoma –⁠ the investigator-initiated phase II GHSG INDIE trial. Hemasphere. 2022; 6 (Suppl): 29.

64. Santarsieri A, Mitchell E, Pham MH, et al. The genomic and clinical consequences of replacing procarbazine with dacarbazine in escalated BEACOPP for Hodgkin lymphoma: a retrospective, observational study. Lancet Oncol. 2025; 26 (1): 98–109. doi: 10.1016/S1470 -⁠ 2045 (24) 00598-9.

65. Ferdinandus J, Schneider G, Moccia A, et al. Fertility in patients with advanced-stage classic Hodgkin lymphoma treated with BrECADD versus eBEACOPP: a secondary analysis of the multicentre, randomised, parallel, open-label, phase 3 HD21 trial. Lancet Oncol. 2025; 26 (8): 1081–1090. doi: 10.1016/S1470-2045 (25) 00262-1.

66. Connors JM, Jurczak W, Straus DJ, et al. Brentuximab vedotin with chemotherapy for stage III or IV Hodgkin’s lymphoma. N Engl J Med. 2018; 378 (4): 331–344. doi: 10.1056/ NEJMoa1708984.

67. Ansell SM, Straus DJ, Connors JM, et al. Seven-year overall survival analysis from ECHELON-1 study of A+AVD versus ABVD in patients with previously untreated stage III/IV classical Hodgkin lymphoma. J Clin Oncol. 2024; 42 (16 Suppl): 7053–7053.

68. Ahmad H Li, Herrera AF, Perry A. Impact of EBV status and histology on outcomes with nivolumab-AVD versus Bv-AVD in patients enrolled on SWOG S1826. Suppl 18th Int Conf Malig Lymphoma Palazzo Dei Congr Lugano Switz 17–21 June 2025. Vol 43; (S3). doi: https: //doi.org/10.1002/hon.70093_20.

69. Belada D, Trněný M, a kolektiv autorů Kooperativní lymfomové skupiny. Diagnostické a léčebné postupy u nemocných s maligními lymfomy –⁠ XV. vydání. Published online 2025.

70. Extermann M, Hurria A. Comprehensive geriatric assessment for older patients with cancer. J Clin Oncol. 2007; 25 (14): 1824–1831. doi: 10.1200/JCO.2007.10.6559.

71. Li D, Soto-Perez-de-Celis E, Hurria A. Geriatric assessment and tools for predicting treatment toxicity in older adults with cancer. Cancer J Sudbury Mass. 2017; 23 (4): 206–210. doi: 10.1097/PPO.0000000000000269.

72. Wildiers H, Heeren P, Puts M, et al. International Society of Geriatric Oncology consensus on geriatric assessment in older patients with cancer. J Clin Oncol. 2014; 32 (24): 2595–2603. doi: 10.1200/JCO.2013.54.8347.

73. Azambuja E, Fleck JF, Batista RG, Menna Barreto SS. Bleomycin lung toxicity: who are the patients with increased risk? Pulm Pharmacol Ther. 2005; 18 (5): 363–366. doi: 10.1016/j.pupt.2005.01.007.

74. Rutherford SC, Li H, Herrera AF, et al. Nivolumab-AVD is better tolerated and improves progression-free survival compared to Bv-AVD in older patients (aged ≥60 years) with advanced stage Hodgkin lymphoma enrolled on SWOG S1826. Blood. 2023; 142 (Suppl 1): 181–181. doi: 10.1182/blood-2023-180114.

75. Rutherford SC, Li H, Herrera AF, et al. Nivolumab-AVD versus brentuximab vedotin–AVD in older patients with advanced-stage classic Hodgkin lymphoma enrolled on S1826. J Clin Oncol. 2025; 0 (0): JCO-25-00204. doi: 10.1200/ JCO-25-00204.

76. Ferdinandus J, Kaul H, Fosså A, et al. PET-guided Brecadd in older patients with advanced-stage classic Hodgkin lymphoma: results of the phase 2 part of the GHSG HD21 trial. Blood. 2024; 144 (Suppl 1): 568–568. doi: 10.1182/ blood-2024-207946.

77. Ferdinandus J, Kaul H., Fossa A. T076: feasibility and efficacy of PET-guided BRECADD in older patients with advanced-stage classical Hodgkin lymphoma: the older cohort of the international GHSG HD21 trial. 13th Int Symp Hodgkin Lymphoma Oct 2024. Published online October 2024. doi: https: //doi.org/10.1002/hem3.70012.

78. Forero-Torres A, Holkova B, Goldschmidt J, et al. Phase 2 study of frontline brentuximab vedotin monotherapy in Hodgkin lymphoma patients aged 60 years and older. Blood. 2015; 126 (26): 2798–2804. doi: 10.1182/blood -⁠ 2015-06-644336.

79. Friedberg JW, Forero-Torres A, Bordoni RE, et al. Frontline brentuximab vedotin in combination with dacarbazine or bendamustine in patients aged ≥60 years with HL. Blood. 2017; 130 (26): 2829–2837. doi: 10.1182/blood -⁠ 2017-06-787200.

80. Evens AM, Advani RH, Helenowski IB, et al. Multicenter phase II study of sequential brentuximab vedotin and doxorubicin, vinblastine, and dacarbazine chemotherapy for older patients with untreated classical Hodgkin lymphoma. J Clin Oncol. 2018; 36 (30). doi: 10.1200/JCO.2018.79.0139.

81. Cheson BD, Bartlett NL, LaPlant B, et al. Brentuximab vedotin plus nivolumab as first-line therapy in older or chemotherapy-ineligible patients with Hodgkin lymphoma (ACCRU): a multicentre, single-arm, phase 2 trial. Lancet Haematol. 2020; 7 (11): e808–e815. doi: 10.1016/S2352-3026 (20) 30275-1.

82. Boell B, Fosså A, Goergen H, et al. B-CAP (brentuximab vedotin, cyclophosphamide, doxorubicin and predniso (lo) Ne) in older patients with advanced-stage Hodgkin lymphoma: results of a phase II intergroup trial by the German Hodgkin Study Group (GHSG) and the Nordic Lymphoma Group (NLG). Blood. 2018; 132 (Suppl 1): 926–926. doi: 10.1182/blood-2018-99-119363.

83. Böll B, Plütschow A, Bürkle C, et al. Doxorubicin, vinblastine, dacarbazine and lenalidomide for older Hodgkin lymphoma patients: final results of a German Hodgkin Study Group (GHSG) phase-I trial. Br J Haematol. 2019; 185 (1): 42–52. doi: 10.1111/bjh.15741.

84. Ansell SM. Hodgkin lymphoma: 2023 update on diagnosis, risk-stratification, and management. Am J Hematol. 2022; 97 (11): 1478–1488. doi: 10.1002/ajh.26717.

85. Moskowitz CH, Nademanee A, Masszi T, et al. Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin’s lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015; 385 (9980): 1853–1862. doi: 10.1016/S0140-6736 (15) 60165-9.

86. Crump M. Management of Hodgkin lymphoma in relapse after autologous stem cell transplant. Hematol Am Soc Hematol Educ Program. Published online 2008 : 326–333. doi: 10.1182/asheducation-2008.1.326.

87. LaCasce AS, Bociek RG, Sawas A, et al. Three-year outcomes with brentuximab vedotin plus bendamustine as first salvage therapy in relapsed or refractory Hodgkin lymphoma. Br J Haematol. 2020; 189 (3): e86–e90. doi: 10.1111/bjh.16499.

88. Lynch RC, Cassaday RD, Smith SD, et al. Dose-dense brentuximab vedotin plus ifosfamide, carboplatin, and etoposide for second-line treatment of relapsed or refractory classical Hodgkin lymphoma: a single centre, phase 1/2 study. Lancet Haematol. 2021; 8 (8): e562–e571. doi: 10.1016/S2352-3026 (21) 00170-8.

89. Kersten MJ, Driessen J, Zijlstra JM, et al. Combining brentuximab vedotin with dexamethasone, high-dose cytarabine and cisplatin as salvage treatment in relapsed or refractory Hodgkin lymphoma: the phase II HOVON/LLPC Transplant BRaVE study. Haematologica. 2021; 106 (4): 1129–1137. doi: 10.3324/ haematol.2019.243238.

90. Cole PD, McCarten KM, Pei Q, et al. Brentuximab vedotin with gemcitabine for paediatric and young adult patients with relapsed or refractory Hodgkin’s lymphoma (AHOD1221): a Children’s Oncology Group, multicentre single-arm, phase 1-2 trial. Lancet Oncol. 2018; 19 (9): 1229–1238. doi: 10.1016/S1470-2045 (18) 30426-1.

91. Advani RH, Moskowitz AJ, Bartlett NL, et al. Brentuximab vedotin in combination with nivolumab in relapsed or refractory Hodgkin lymphoma: 3-year study results. Blood. 2021; 138 (6): 427–438. doi: 10.1182/blood.2020009178.

92. Bryan LJ, Casulo C, Allen PB, et al. Pembrolizumab added to ifosfamide, carboplatin, and etoposide chemotherapy for relapsed or refractory classic Hodgkin lymphoma: a multi-institutional phase 2 investigator-initiated nonrandomized clinical trial. JAMA Oncol. 2023; 9 (5): 683–691. doi: 10.1001/jamaoncol.2022.7975.

93. Moskowitz AJ, Shah G, Schöder H, et al. Phase II trial of pembrolizumab plus gemcitabine, vinorelbine, and liposomal doxorubicin as second-line therapy for relapsed or refractory classical Hodgkin lymphoma. J Clin Oncol. 2021; 39 (28): 3109–3117.

94. Mei M, Palmer J, Lee HJ, et al. Nivolumab plus ifosfamide, carboplatin, and etoposide are a highly effective first salvage regimen in high-risk relapsed/refractory Hodgkin lymphoma. HemaSphere. 2025; 9 (5): e70126. doi: 10.1002/hem3.70126.

95. Santoro A, Mazza R, Pulsoni A, et al. Five-year results of the BEGEV salvage regimen in relapsed/refractory classical Hodgkin lymphoma. Blood Adv. 2020; 4 (1): 136–140. doi: 10.1182/bloodadvances.2019000984.

96. Josting A, Müller H, Borchmann P, et al. Dose intensity of chemotherapy in patients with relapsed Hodgkin’s lymphoma. J Clin Oncol. 2010; 28 (34): 5074–5080. doi: 10.1200/ JCO.2010.30.5771.

97. Moskowitz A, Shah GL, Ganesan N, et al. Pembrolizumab maintenance instead of autologous hematopoietic cell transplantation for patients with relapsed or refractory Hodgkin lymphoma in complete response after pembrolizumab, gemcitabine, vinorelbine, and liposomal doxorubicin. Blood. 2024; 144 (Suppl 1): 569–569. doi: 10.1182/blood-2024-202537.

98. Sureda Balarí AM, Nuñez Cespedes J, Terol Castera MJ, et al. The addition of brentuximab vedotin to ESHAP significantly increases the rate of metabolic complete remissions vs chemotherapy alone in patients with relapsed/refractory classical Hodgkin’s lymphoma. Final results of a phase IIb prospective randomized clinical trial (BRESELIBET). Blood. 2024; 144 (Suppl 1): 3049–3049. doi: 10.1182/blood-2024-211527.

99. Moskowitz CH, Walewski J, Nademanee A, et al. Five-year PFS from the AETHERA trial of brentuximab vedotin for Hodgkin lymphoma at high risk of progression or relapse. Blood. 2018; 132 (25): 2639–2642. doi: 10.1182/blood -⁠ 2018-07-861641.

100. Armand P, Chen YB, Redd RA, et al. PD-1 blockade with pembrolizumab for classical Hodgkin lymphoma after autologous stem cell transplantation. Blood. 2019; 134 (1): 22–29. doi: 10.1182/blood.2019000215.

101. Aijaz P, Basharat A, Akram U, et al. Outcomes with nivolumab maintenance after autologous hematopoietic stem cell transplantation in relapsed/refractory Hodgkin lymphoma: A systematic review and meta-analysis. J Clin Oncol. 2025; 43 (16 Suppl): e19037–e19037.

102. Sureda A, García-Sanz R, Domingo-Domenech E, et al. Retreatment with brentuximab vedotin in patients with relapsed/refractory CD30+ malignancies: a retrospective medical chart review study in Spain –⁠ the BELIEVE study. Cancers. 2025; 17 (7). doi: 10.3390/cancers17071137.

103. Martinez Munoz MC, Khvedelidze I, Fekom M, et al. Outcomes of patients with Hodgkin lymphoma receiving brentuximab vedotin (BV) as maintenance therapy after ASCT according to previous exposure to BV a retrospective analysis of the EBMT Lymphoma Working Party in collaboration with Geltamo, FIL, Lysarc, and Turkish Lymphoma Group. Blood. 2024; 144 (Suppl 1): 1663–1663. doi: 10.1182/blood-2024-205007.

104. Bazarbachi A, Boumendil A, Finel H, et al. The outcome of patients with Hodgkin lymphoma and early relapse after autologous stem cell transplant has improved in recent years. Leukemia. 2022; 36 (6): 1646–1653. doi: 10.1038/s41375-022-01563-8.

105. Armand P, Zinzani PL, Lee HJ, et al. Five-year follow-up of KEYNOTE-087: pembrolizumab monotherapy for relapsed/refractory classical Hodgkin lymphoma. Blood. 2023; 142 (10): 878–886. doi: 10.1182/blood.2022019386.

106. Ansell SM, Bröckelmann PJ, von Keudell G, et al. Nivolumab for relapsed/refractory classical Hodgkin lymphoma: 5-year survival from the pivotal phase 2 CheckMate 205 study. Blood Adv. 2023; 7 (20): 6266–6274. doi: 10.1182/bloodadvances.2023010334.

107. Kuruvilla J, Ramchandren R, Santoro A, et al. Pembrolizumab versus brentuximab vedotin in relapsed or refractory classical Hodgkin lymphoma (KEYNOTE-204): an interim analysis of a multicentre, randomised, open-label, phase 3 study. Lancet Oncol. 2021; 22 (4): 512–524. doi: 10.1016/S1470-2045 (21) 00005-X.

108. Fedorova LV, Lepik KV, Mikhailova NB, et al. Nivolumab discontinuation and retreatment in patients with relapsed or refractory Hodgkin lymphoma. Ann Hematol. 2021; 100 (3): 691–698. doi: 10.1007/s00277-021-04429-8.

109. Chen R, Zinzani PL, Fanale MA, et al. Phase II study of the efficacy and safety of pembrolizumab for relapsed/refractory classic Hodgkin lymphoma. J Clin Oncol. 2017; 35 (19): 2125–2132. doi: 10.1200/JCO.2016.72.1316.

110. Diefenbach CS, Hong F, Ambinder RF, et al. Ipilimumab, nivolumab, and brentuximab vedotin combination therapies in patients with relapsed or refractory Hodgkin lymphoma: phase 1 results of an open-label, multicentre, phase 1/2 trial. Lancet Haematol. 2020; 7 (9): e660–e670. doi: 10.1016/S2352-3026 (20) 30221-0.

111. Ramos CA, Grover NS, Beaven AW, et al. Anti-CD30 CAR-T cell therapy in relapsed and refractory Hodgkin lymphoma. J Clin Oncol. 2020; 38 (32): 3794–3804. doi: 10.1200/JCO. 20.01342.

112. Nieto Y, Banerjee P, Kaur I, et al. Innate cell engager (ICE^®) AFM13 combined with preactivated and expanded (P+ E) cord blood (CB) -derived natural killer (NK) cells for patients with refractory CD30-positive lymphomas: final results. Blood. 2023; 142 (Suppl 1): 774–774.

113. Johnson P, Federico M, Kirkwood A, et al. Adapted treatment guided by interim PET-CT scan in advanced Hodgkin’s lymphoma. N Engl J Med. 2016; 374 (25): 2419–2429. doi: 10.1056/NEJMoa1510093.

114. ClinicalTrials.gov. Response adapted incorporation of tislelizumab into frontline therapy of older patients with Hodgkin lymphoma (RATiFY). Identifier: NCT05627115. Available from: https: //clinicaltrials.gov/ct2/show/NCT05627115. Accessed 4 Aug 2025.

Podíl autorů na přípravě rukopisu

Alice Sýkorová 60 %, Heidi Móciková 30 %, Vít Procházka 10 %. Celý rukopis napsala Alice Sýkorová, připomínkovala Heidi Móciková a Vít Procházka.

Prohlášení o konfliktu zájmů

AS –⁠ poradenská činnost: Takeda, Bristol-Myers Squibb, Merck Sharp & Dohme

HM –⁠ poradenská činnost: Takeda, Bristol-Myers Squibb, Merck Sharp & Dohme

VP –⁠ poradenská činnost: Takeda, Bristol-Myers Squibb, Merck Sharp & Dohme

Poděkování

Tato práce byla realizována za podpory Agentury pro zdravotnický výzkum MZ ČR –⁠ grantové číslo: NU22-03-00182, za podpory programu Cooperatio –⁠ výzkumná oblast onkologie a hematologie, dále za podpory MZČR –⁠ DRO (FNOL, 00098892).

Prohlášení o použití AI

AI byla použita k vyhledávání citací k dané problematice a překladu do anglického jazyka.