Léčba pacientů s Hodgkinovým lymfomem po relapsu nebo progresi onemocnění – chemosenzitivita, transplantace a cílená léčba

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Autoři: O. Novosad; T. Rudiuk
Působiště autorů: Oncohaematology Department, National Cancer Institute, Kyiv, Ukraine
Vyšlo v časopise: Transfuze Hematol. dnes,29, 2023, No. 2, p. 100-105.
Kategorie: Souhrnné/edukační práce
doi: https://doi.org/10.48095/cctahd2023prolekare.cz8

Souhrn

Dnes se Hodgkinův lymfom (HL) považuje za vyléčitelnou nemoc, protože až 90 % pacientů v časném stadiu a 70–80 % v pokročilých stadiích onemocnění dosáhne po léčbě první linie dlouhodobé remise. Přibližně 15–25 % pacientů s HL má primárně refrakterní nemoc nebo zrelabuje poté, co dosáhne odpověď po léčbě první linie. Přibližně polovina těchto nemocných je chemozenzitivních a/nebo zrelabuje po transplantaci. Vysocedávkovaná chemoterapie s autologní transplantací kmenových buněk má u pacientů s refrakterním onemocněním nebo relapsem vysokou účinnost a přispívá k dlouhodobému přežívání u významného počtu nemocných. Pacienti s vysoce rizikovým onemocněním, kteří byli léčeni načas a nedosáhli dostatečnou odpověď po standardní léčbě první linie nebo pacienti s chemozenzitivním relapsem mají dobrou prognózu. Na druhé straně, vysocedávkovaná chemoterapie následovaná autologní transplantací kmenových buněk není optimální možností u pacientů s primárně refrakterním onemocněním nebo s chemorezistentním relapsem. Alogenní transplantace krvetvorných buněk a/nebo cílená imunoterapie reprezentují léčebné možnosti pro tuto skupinu nemocných.

Klíčová slova:

transplantace – Hodgkinův lymfom – relaps – cílená léčba – chemosensitivita

Zdroje

novosad.o.ua@gmail.com1. Viviani S, Zinzani PL, Rambaldi A, et al. ABVD versus BEACOPP for Hodgkin’s lymphoma when high -⁠ dose salvage is planned. New Engl J Med. 2011; 365 (3): 203–212. doi: 10.1056/NEJMoa1100340.

2. Novosad O, Skrypets T, Pastushenko I, et al. A Ukrainian multicenter prospective study of the value of PET/ CT prognostic role in primary patients with Hodgkins lymphoma in a real-life cohort. Klin Onkol. 2020; 33 (6): 450–457.

3. Johnson P, Federico M, Kirkwood A, et al. (2016). 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/NEJMoa1510093.

4. Novosad OI, Kriachok IA, Grabovyy OM, Antonuk SA. Prognostic risk factors for newly diagnosed patients with advanced stages classical Hodgkin`s lymphoma. Lik Sprava. 2014; (9-10): 88–94. doi: 10.1056/NEJMoa1408648.

5. Федоренко ЗП, Гулак ЛО, Михайлович ЮЙ, Горох ЄЛ, Рижов АЮ, Сумкіна ОВ, Куценко ЛБ. Рак в Україні, 2020–2021. Захворюваність, смертність, показники діяльності онкологічної служби. Бюлетень Національного Канцер-реєстру України. 2022; 22 : 101.

6. Schmitz N, Pfistner B, Sextro M, 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. doi: 10.1016/S0140-6736 (02) 08938-9.

7. 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. doi: 10.1016/0140-6736 (93) 92411 -⁠ l.

8. Moskowitz CH, Kewalramani T, Nimer SD, Gonzalez M, Zelenetz AD, Yahalom J. Effectiveness of high dose chemoradiotherapy and autologous stem cell transplantation for patients with biopsy-proven primary refractory Hodgkin’s disease. Br J Haematol. 2004; 124 : 645–652. doi: 10.1111/j.1365-2141.2003.04828.x.

9. Sirohi B, Cunningham D, Powles R, Murphy F, Arkenau T, Norman A. Long-term outcome of autologous stem-cell transplantation in re -⁠ lapsed or refractory Hodgkin’s lymphoma. Ann Oncol. 2008; 19 : 1312–1319. doi: 10.1093/annonc/ mdn052.

10. Moskowitz CH, Nimer SD, Zelenetz AD, et al. A 2-step comprehensive high-dose chemoradio -⁠ therapy second-line program for relapsed and refractory Hodgkin disease: analysis by intent to treat and development of a prognostic model. Blood. 2001; 97 : 616–623. doi: 10.1182/ blood.v97.3.616.

11. Moskowitz AJ, Schöder H, Gavane S, et al. Baseline metabolic tumor volume is an independent prognostic factor for relapsed and refractory Hodgkin lymphoma patients receiving PET -⁠ adapted salvage therapy with brentuximab vedotin and augmented ICE. Hematol Oncol. 2017; 35 (suppl 2): 36–37. doi: 10.1182/blood-2017-06-788877.

12. Moskowitz CH, Matasar MJ, Zelenetz AD, et al. (2012). Normalization of pre-ASCT, FDG-PET imaging with second-line, non -⁠ cross-resistant, chemotherapy programs improves event-free survival in patients with Hodgkin lymphoma. Blood. 2012; 119 : 1665–1670. doi: 10.1182/blood-2011-10-388058.

13. Gentzler RD, Evens AM, Rademaker AW, et al. F-18 FDG-PET predicts outcomes for patients receiving total lymphoid irradiation and autologous blood stem-cell transplantation for relapsed and refractory Hodgkin lymphoma. Br J Haematol. 2014; 165 : 793–800. doi: 10.1111/bjh.12824.

14. Akhtar S, Al-Sugair AS, Abouzied M, et al. Pre-transplant FDG-PET-based survival model in relapsed and refractory Hodgkin’s lymphoma: outcome after high -⁠ dose chemotherapy and auto -⁠ SCT. Bone Marrow Transplant. 2013; 48 : 1530–1536. doi: 10.1038/bmt.2013.88.

15. Martínez C, Canals C, Sarina B, et al. Identification of prognostic factors predicting outcome in Hodgkin’s lymphoma patients relapsing after autologous stem cell transplantation. Ann Oncol. 2013; 24 (9): 2430–2434. doi: 10.1093/annonc/mdt206.

16. Hagenbeek A, Zijlstra J M, Plattel WJ, et al. Combining brentuximab vedotin with DHAP as salvage treatment in relapsed/refractory Hodgkin lymphoma: the phase II HOVON/LLPC transplant BRaVE study. Blood. 2021; 106 (4): 1129–1137. doi: 10.3324/haematol.2019.243238.

17. Garcia-Sanz R, Sureda A, De La Cruz F, et al. Brentuximab vedotin and ESHAP is highly effective as second-line therapy for Hodgkin lymphoma patients (long-term results of a trial by the Spanish GELTAMO group). Ann Oncol. 2019; 30 : 612–620. doi: 10.1093/annonc/mdz009.

18. Lacasce AS, Bociek R G, Sawas A, et al. Brentuximab vedotin plus bendamustine: a highly active first salvage regimen for relapsed or refractory Hodgkin lymphoma. Blood. 2018; 132 : 40–48. doi: 10.1182/blood-2017-11-815183.

19. Herrera AF, Moskowitz AJ, Bartlett NL, et al. Interim results of brentuximab vedotin in combina -⁠ tion with nivolumab in patients with relapsed or refractory Hodgkin lymphoma. Blood. 2018; 131 : 1183–1194. doi: 10.1182/blood -⁠ 2017-10-811224.

20. Takeda Pharmaceuticals. (Adcetris) summary of product characteristics. (2018). Retrieved from https: //www.ema.europa.eu/ en/documents/productinforma -⁠ tion/adcetris -⁠ epar-product-information_ en.pdf. Accessed 1 Jan 2020.

21. 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 : 2183–2189. doi: 10.1200/JCO.2011.38.0410.

22. Chen R, Gopal AK, Smith SE, et al. Five-year survival and durability results of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma. Blood. 2016; 28 : 1562–1566. doi: 10.1182/blood-2016-02-699850.

23. Walewski J, Hellmann A, Siritanaratkul N, et al. Prospective study of brentuximab ve -⁠ dotin in relapsed/refractory Hodgkin lymphoma patients who are not suitable for stem cell transplant or multi-agent chemotherapy. Br J Haematol. 2018; 183 : 400–410. doi: 10.1111/bjh. 15539.

24. Chen R, Palmer JM, Martin P, et al. Results of a multicenter phase II trial of brentuximab vedotin as second-line therapy before autologous transplantation in relapsed/refractory Hodgkin lymphoma. Biol Blood Marrow Transplant. 2015; 21 : 2136–2140. doi: 10.1016/j.bbmt.2015.07.018.

25. Perales M-A, Ceberio I, Armand P, et al. Role of cytotoxic therapy with hematopoietic cell transplanta -⁠ tion in the treatment of Hodgkin lymphoma: guidelines from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2015; 21 (6): 971–983. doi: 10.1016/j.bbmt.2015.02.022.

26. Ghosh N, Karmali R, Rocha V, et al. Reduced-intensity transplantation for lymphomas using haploidentical related donors versus HLA-matched sibling donors: a Center for International Blood and Marrow Transplant research analysis. J Clin Oncol. 2016; 34 (26): 3141–3149. doi: 10.1200/JCO.2015.66.3476.

27. Martínez C, Gayoso J, Canals C, et al. Post-transplantation cyclophosphamide-based haploidentical transplantation as alternative to matched sibling or unrelated donor transplantation for Hodgkin lymphoma: a registry study of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation. J Clin Oncol. 2017; 35 (30): 3425–3432. doi: 10.1200/JCO.2017.72.6869.

28. Castagna L, Bramanti S, Devillier R, et al. Haploidentical transplantation with post-infusion cyclophosphamide in advanced Hodgkin lymphoma. Bone Marrow Transplant. 2017; 52 (5): 683–688. doi: 10.1038/bmt.2016.348.

29. Messer M, Steinzen A, Vervölgyi E, et al. Unrelated and alternative donor allogeneic stem cell trans -⁠ plant in patients with relapsed or refractory Hodgkin lymphoma: a systematic review. Leuk Lymphoma. 2014; 55 (2): 296–306. doi: 10.3109/10428194.2013.802780.

30. Majhail NS, Weisdorf DJ, Wagner JE, et al. Comparable results of umbilical cord blood and HLA-matched sibling donor hematopoietic stem cell transplantation after reduced-intensity pre -⁠ parative regimen for advanced Hodgkin lymphoma. Blood. 2006; 107 (9): 3804–3807. doi: 10.1182/blood-2005-09-3827.

31. Karantanos T, Politikos I, Boussiotis VA. Advances in the patho -⁠ physiology and treatment of relapsed/refractory Hodgkin’s lymphoma with an emphasis on targeted therapies and transplantation strategies. Blood Lymphatic Cancer. 2017; 7 : 37–52. doi: 10.2147/BLCTT.S105458.

32. Thompson PA, Perera T, Marin D, et al. Double umbilical cord blood transplant is effective therapy for relapsed or refractory Hodgkin lymphoma. Leuk Lymphoma. 2016; 57 (7): 1607–1615. doi: 10.3109/10428194.2015.1105370.

33. Moskowitz AJ, Perales M-A, Kewalramani T, et al. Outcomes for patients who fail high dose chemoradiotherapy and autologous stem cell rescue for relapsed and primary refractory Hodgkin lymphoma. Br J Haematol. 2009; 146 (2): 158–163. doi: 10.1111/j.1365-2141.2009.077 27.x.

34. Khan N, Moskowitz AJ. Where do the new drugs fit in for re -⁠ lapsed/refractory Hodgkin lymphoma? Curr Hematol Malign Rep. 2017; 12 (3): 227–233. doi: 10.1007/s11899-017 -⁠ 0384-z.

35. Borchmann S, von Tresckow B. Novel agents in classical Hodgkin lymphoma. Leuk Lymphoma. 2017; 58 (10): 2275–2286. doi: 10.1111/bjh.15695.

36. Jethava Y, Guru Murthy GS, Hamadani M. Relapse of Hodgkin lymphoma after autologous transplantation: Time to rethink treatment? Hematol Oncol Stem Cell Ther. 2017; 10 (2): 47–56. doi: 10.1016/j.hemonc.2016.12.002.

37. Fanale M, Engert A, Younes A, et al. Nivolumab for relapsed/refractory classical Hodgkin lymphoma after autologous transplant: full results after extended follow-up of the phase 2 Check-mate 205 trial. Hematol Oncol. 2017; 35 (2): 135–136. doi: 10.1200/JCO.2017.76. 0793.

38. Timmerman JM, Engert A, Younes A, et al. Checkmate 205 update with minimum 12-month follow up: a phase 2 study of nivolumab in patients with relapsed/refractory classical Hodgkin lymphoma. Blood. 2016; 128 (22): 1110. doi.org/10.1182/blood.V128.22.1110.1110.

39. Armand P, Shipp MA, Ribrag V, et al. Programmed death-1 blockade with pembrolizumab in patients with classical Hodgkin lymphoma after brentuximab vedotin failure. J Clin Oncol. 2016; 34 (31): 3733–3739. doi: 10.1200/JCO. 2016.67.3467.

40. 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.

41. Chen R, Gibb AL, Collins GP, et al. Blockade of the PD-1 checkpoint with anti-PD-L1 antibody avelumab is sufficient for clinical activity in relapsed/refractory classical Hodgkin lymphoma (CHL). Hematol Oncol. 2017; 35 (2): 67. doi.org/10.1002/hon.2437.

42. Kirschbaum MH, Goldman BH, Zain JM, et al. A phase 2 study of vorinostat for treatment of relapsed or refractory Hodgkin lymphoma: Southwest Oncology Group Study S0517. Leuk Lymphoma. 2012; 53 (2): 259–262. doi: 10.3109/10428194.2011.608448.

43. Younes A, Sureda A, Ben-Yehuda D, et al. Panobinostat in patients with relapsed/refractory Hodgkin’s lymphoma after autologous stem-cell transplantation: results of a phase II study. J Clin Oncol. 2012; 30 (18): 2197–2203. doi: 10.1200/JCO.2011.38.1350.

44. DeAngelo DJ, Spencer A, Bhalla KN, et al. Phase Ia/II, two-arm, open-label, dose-escalation study of oral panobinostat administered via two dosing schedules in patients with advanced hematologic malignancies. Leukemia. 2013; 27 (8): 1628–1636. doi: 10.1038/leu.2013.38.

45. Younes A, Oki Y, Bociek RG, et al. Mocetinostat for relapsed classical Hodgkin’s lymphoma: an open-label, single-arm, phase 2 trial. Lancet Oncol. 2011; 12 (13): 1222–1228. doi: 10.1016/ S1470-2045 (11) 70265-0.

46. Shah GL, Moskowitz CH. Transplant strategies in relapsed/refractory Hodgkin lymphoma. Blood. 2018; 131 (15): 1689–1697. doi: 10.1182/blood-2017-09-772673.