Hodgkin´s Lymhoma – the Treatment Aproaches Development and Current Trends

Czech version

Authors: J. Kořen; M. Trněný
Authors‘ workplace: I. interní klinika – klinika hematologie 1. LF UK a VFN v Praze
Published in: Klin Onkol 2015; 28(Supplementum 3): 87-94
doi: https://doi.org/10.14735/amko20153S87

Overview

Hodgkin’s lymphoma is a relatively rare malignant disease, mostly affecting younger adults. It represents one of the most curable disease among all lymphomas and other malignant diseases of adult age, with curability more than 80%. The progress of curability and long term survival demonstrates the development of oncologic approach during the last few decades, depicted in this article, particularly by introduction of combined modality treatment (chemotherapy and radiotherapy), progress in radiotherapy technique, implementation of high intensity regimens for advanced stages and use of novel drugs as well. Because of high curability rate and young age of most of the patients, late toxic effects are of significant relevance. The ongoing clinical research is focused on better prognostic stratification offering the patients more individualized treatment by risk and response disease evaluation, aiming to reduce toxicity while maintaining high curability and introduction of novel, less toxic drugs and their use in early phases of treatment.

Key words:
Hodgkin’s lymphoma – induction chemotherapy – salvage therapy – combined modality therapy – hematopoietic stem cell transplantation – positron-emission tomography – brentuximab vedotin – nivolumab

This study was supported by grants of Internal Grant Agency of the Czech Ministry of Health No. NT13072-4/2012 and NT12193-5/2011.

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Submitted:
27. 9. 2015

Accepted:
1. 10. 2015

Sources

1. Küppers R, Rajewsky K, Zhao M et al. Hodgkin disease: Hodgkin and Reed‑ Sternberg cells picked from histological sections show clonal immunoglobulin gene rearrangements and appear to be derived from B cellsat various stages of development. Proc Natl Acad Sci U S A 1994; 91(23): 10962– 10966.

2. Schmitz R, Stanelle J, Hansmann ML et al. Pathogenesis of classical and lymphocyte‑ predominant Hodgkin lymphoma. Annu Rev Pathol 2009; 4: 151– 174. doi: 10.1146/ annurev.pathol.4.110807.092209.

3. Engert A, Franklin J, Eich HT et al. Two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine plus extended‑ field radiotherapy is superior to radiotherapy alone in early favorable Hodgkin’s lymphoma: final results of the GHSG HD7 trial. J Clin Oncol 2007; 25(23): 3495– 3502.

4. Hagenbeek A, Eghbali H, Ferme C et al. Three cycles of MOPP/ ABV hybrid and involved‑ field irradiation is more effective than subtotal nodal irradiation in favorable supradiaphragmatic clinical stage I– II Hodgkin’s dinase. Blood 2000; 96: A575.

5. Engert A, Plütschow A, Eich HT 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.

6. Hutchings M, Loft A, Hansen M et al., FDG‑ PET after two cycles of chemotherapy predicts treatment failure and progression‑free survival in Hodgkin lymphoma. Blood 2006; 107(1): 52– 59.

7. 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; 372(17): 1598– 1607. doi: 10.1056/ NEJMoa1408648.

8. Raemaekers JM, André MP, Federico M et al. Omitting radiotherapy in early positron emission tomography‑ negative stage I/ II Hodgkin lymphoma is associated with an increased risk of early relapse: clinical results of the preplanned interim analysis of the randomized EORTC/ LYSA/ FIL H10 trial. J Clin Oncol 2014; 32(12): 1188– 1194. doi: 10.1200/ JCO.2013.51.9298.

9. Eghbali H, Raemaekers J, Carde P. The EORTC strategy in the treatment of Hodgkin‘s lymphoma. Eur J Haematol Suppl 2005; (66): 135– 140.

10. Engert A, Schiller P, Josting A et al. Involved‑ field radiotherapy is equally effective and less toxic compared with extended‑ field radiotherapy after four cycles of chemotherapy in patients with early‑stage unfavorable Hodgkin‘s lymphoma: results of the HD8 trial of the German Hodgkin‘s Lymphoma Study Group. J Clin Oncol 2003; 21(19): 3601– 3608.

11. Eich HT, Diehl V, Engert A 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.

12. Noordijk EM, Thomas J, Fermé C et al. First results of the EORTC‑ GELA H9 randomized trials: the H9- F trial (comparing 3 radiation dose levels) and H9- U trial (comparing 3 chemotherapy schemes) in patients with favorable or unfavorable early stage Hodgkin’s lymphoma (HL). J Clin Oncol 2005 ASCO Annual Meeting Proceedings 2005; 23 (part I of II): 16S.

13. von Tresckow B, Plütschow A, Engert A 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.

14. DeVita VT Jr, Simon RM, Hubbard SM et al. Curability of advanced Hodgkin‘s disease with chemotherapy. Long‑term follow‑up of MOPP‑treated patients at the National Cancer Institute. Ann Intern Med 1980; 92(5): 587– 595.

15. Santoro A, Bonadonna G, Valagussa P et al. Long‑term results of combined chemotherapy‑ radiotherapy approach in Hodgkin’s disease: superiority of ABVD plus radiotherapy versus MOPP plus radiotherapy. J Clin Oncol 1987; 5(1): 27– 37.

16. Johnson PW, Radford JA, Cullen MH et al. Comparison of ABVD and alternating or hybrid multidrug regimens for the treatment of advanced Hodgkin’s lymphoma: results of the United Kingdom Lymphoma Group LY09 Trial (ISRCTN97144519). J Clin Oncol 2005; 23(36): 9208– 9218.

17. Hoskin PJ, Lowry L, Horwich A et al. Randomized comparison of the Stanford V regimen and ABVD in the treatment of advanced Hodgkin’s lymphoma: United Kingdom National Cancer Research Institute Lymphoma Group Study ISRCTN 64141244. J Clin Oncol 2009; 27(32): 5390– 5396. doi: 10.1200/ JCO.2009.23.3239.

18. 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.

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

20. Skoetz N, Trelle S, Rancea M et al. Effect of initial treatment strategy on survival of patients with advanced‑stage Hodgkin’s lymphoma: a systematic review and network meta‑analysis. Lancet Oncol 2003; 14(10): 943– 952. doi: 10.1016/ S1470‑ 2045(13)70341‑ 3.

21. Linch DC, Winfield D, Goldstone AH et al. Dose intensification with autologous bone‑ marrow transplantation in relapsed and resistant Hodgkin‘s disease: results of a BNLI randomised trial. Lancet 1993; 341(8852): 1051– 1054.

22. Schmitz N, Pfistner B, Diehl V et al. Aggressive conventional chemotherapy compared with high‑dose chemotherapy with autologous haemopoietic stem‑ cell transplantation for relapsed chemosensitive Hodgkin‘s disease: a randomised trial. Lancet 2002; 359(9323): 2065– 2071.

23. Bartlett NL, Niedzwiecki D, Johnson JL et al. Gemcitabine, vinorelbine, and pegylated liposomal doxorubicin (GVD), a salvage regimen in relapsed Hodgkin‘s lymphoma: CALGB 59804. Ann Oncol 2007; 18(6): 1071– 1079.

24. Moskowitz AJ, Hamlin PA Jr, Perales MA. hase II study of bendamustine in relapsed and refractory Hodgkin lymphoma. J Clin Oncol 2013; 31(4): 456– 460. doi: 10.1200/ JCO.2012.45.3308.

25. Sirohi B, Cunningham D, Powles R et al. Long‑term outcome of autologous stem‑ cell transplantation in relapsed or refractory Hodgkin‘s lymphoma. Ann Oncol 2008; 19(7): 1312– 1319. doi: 10.1093/ annonc/ mdn052.

26. Mocikova H, Pytlik R, Markova J et al. Pre‑transplant positron emission tomography in patients with relapsed Hodgkin lymphoma. Leuk Lymphoma 2011; 52(9): 1668– 1674. doi: 10.3109/ 10428194.2011.573889.

27. 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.

28. Morschhauser F, Brice P, Fermé C et al. Risk‑adapted salvage treatment with single or tandem autologous stem‑ cell transplantation for first relapse/ refractory Hodgkin‘s lymphoma: results of the prospective multicenter H96 trial by the GELA/ SFGM study group. J Clin Oncol 2008; 26(36): 5980– 5987. doi: 10.1200/ JCO.2007.15.5887.

29. Peniket AJ, Ruiz de Elvira MC, Taghipour G et al. An EBMT registry matched study of allogeneic stem cell transplants for lymphoma: allogeneic transplantation is associated with a lower relapse rate but a higher procedure‑related mortality than autologous transplantation. Bone Marrow Transplant 2003; 31(8): 667– 678.

30. Sureda A, Canals C, Arranz R et al. Allogeneic stem cell transplantation after reduced intensity conditioning in patients with relapsed or refractory Hodgkin’s lymphoma. Results of the HDR‑ ALlO study – a prospective clinical trial by the Grupo Español de Linfomas/ Trasplante de Médula Osea (GEL/ TAMO) and the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. Haematologica 2012; 97(2): 310– 317. doi: 10.3324/ haematol.2011.045757.

31. 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.

32. Moskowitz C, Nadamanee A, Masszi T et al. The Aethera Trial: results of a Randomized, double‑blind, placebo‑ controlled phase 3 study of brentuximab vedotin in the treatment of patients at risk of progression following autologous stem cell transplant for Hodgkin lymphoma. Blood 2014; 124(21).

33. 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/NEJMoa1411087.