Skip to main content
main-content
Erschienen in: Die Onkologie 10/2022

01.06.2022 | Hodgkin-Lymphom | Leitthema

Das Hodgkin-Lymphom in fortgeschrittenen Stadien

verfasst von: Dr. med. J. Ferdinandus, M. Oertel, D. A. Eichenauer, J. Meissner, A. Engert, P. Borchmann

Erschienen in: Die Onkologie | Ausgabe 10/2022

Einloggen, um Zugang zu erhalten

Zusammenfassung

Hintergrund

Sowohl gemäß der Positronenemissionstomographie (PET-)adaptierte Protokolle als auch neue Substanzen haben in den letzten Jahren Einzug in die Erstlinientherapie des fortgeschrittenen Hodgkin-Lymphoms (HL) gehalten.

Ziel der Arbeit

Diese Arbeit gibt eine Übersicht über die leitliniengerechte Therapie des HL in fortgeschrittenen Stadien und aktuelle Studiendaten.

Material und Methoden

Es handelt sich um eine narrative Übersichtsarbeit.

Ergebnisse

Standardtherapie für Patient*innen bis 60 Jahre mit fortgeschrittenem HL ist eine PET-2-gesteuerte (PET nach 2 Zyklen) Chemotherapie mit 4 Zyklen eBEACOPP (Bleomycin, Etoposid, Doxorubicin, Cyclophosphamid, Vincristin, Procarbazin und Prednison) für PET-2-negative und 6 Zyklen eBEACOPP für PET-2-positive Patient*innen. Diese Therapie hat ein herausragendes Nutzen-Risiko-Verhältnis mit bestmöglicher Lymphomkontrolle, hoher Sicherheit und, für die Mehrheit der Patient*innen, kurzer Therapiedauer von nur 3 Monaten. Patient*innen mit PET-positiven Restbefunden sollen konsolidierend mit 30 Gy bestrahlt werden. Für ältere Patient*innen wird eine Therapie mit 2 Zyklen ABVD (Adriamycin, Bleomycin, Vinblastin und Dacarbazin) mit anschließender Gabe von 4 Zyklen AVD und einer Bestrahlung PET-positiver Reste empfohlen.

Schlussfolgerung

Das HL in fortgeschrittenen Stadien ist in mehr als 90 % der Fälle heilbar. Ziel aktueller Studien ist die weitere individualisierte Reduktion der Toxizität bei Erhalt der Effektivität unter Einbindung von Immuncheckpointinhibitoren.
Literatur
1.
Zurück zum Zitat Allen PB, Savas H, Evens AM et al (2021) Pembrolizumab followed by AVD in untreated early unfavorable and advanced-stage classical Hodgkin lymphoma. Blood 137:1318–1326 CrossRef Allen PB, Savas H, Evens AM et al (2021) Pembrolizumab followed by AVD in untreated early unfavorable and advanced-stage classical Hodgkin lymphoma. Blood 137:1318–1326 CrossRef
2.
Zurück zum Zitat Anderson RA, Remedios R, Kirkwood AA et al (2018) Determinants of ovarian function after response-adapted therapy in patients with advanced Hodgkin’s lymphoma (RATHL): a secondary analysis of a randomised phase 3 trial. Lancet Oncol 19:1328–1337 CrossRef Anderson RA, Remedios R, Kirkwood AA et al (2018) Determinants of ovarian function after response-adapted therapy in patients with advanced Hodgkin’s lymphoma (RATHL): a secondary analysis of a randomised phase 3 trial. Lancet Oncol 19:1328–1337 CrossRef
3.
Zurück zum Zitat Boll B, Bredenfeld H, Gorgen H et al (2011) Phase 2 study of PVAG (prednisone, vinblastine, doxorubicin, gemcitabine) in elderly patients with early unfavorable or advanced stage Hodgkin lymphoma. Blood 118:6292–6298 CrossRef Boll B, Bredenfeld H, Gorgen H et al (2011) Phase 2 study of PVAG (prednisone, vinblastine, doxorubicin, gemcitabine) in elderly patients with early unfavorable or advanced stage Hodgkin lymphoma. Blood 118:6292–6298 CrossRef
4.
Zurück zum Zitat Borchmann P, Goergen H, Kobe C et al (2017) 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 390:2790–2802 CrossRef Borchmann P, Goergen H, Kobe C et al (2017) 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 390:2790–2802 CrossRef
5.
Zurück zum Zitat Borchmann P, Haverkamp H, Lohri A et al (2017) Progression-free survival of early interim PET-positive patients with advanced stage Hodgkin’s lymphoma treated with BEACOPPescalated alone or in combination with rituximab (HD18): an open-label, international, randomised phase 3 study by the German Hodgkin study group. Lancet Oncol 18:454–463 CrossRef Borchmann P, Haverkamp H, Lohri A et al (2017) Progression-free survival of early interim PET-positive patients with advanced stage Hodgkin’s lymphoma treated with BEACOPPescalated alone or in combination with rituximab (HD18): an open-label, international, randomised phase 3 study by the German Hodgkin study group. Lancet Oncol 18:454–463 CrossRef
6.
Zurück zum Zitat Calabresi A, Ferraresi A, Festa A et al (2013) Incidence of AIDS-defining cancers and virus-related and non-virus-related non-AIDS-defining cancers among HIV-infected patients compared with the general population in a large health district of Northern Italy, 1999–2009. HIV Med 14:481–490 CrossRef Calabresi A, Ferraresi A, Festa A et al (2013) Incidence of AIDS-defining cancers and virus-related and non-virus-related non-AIDS-defining cancers among HIV-infected patients compared with the general population in a large health district of Northern Italy, 1999–2009. HIV Med 14:481–490 CrossRef
7.
Zurück zum Zitat Casasnovas RO, Bouabdallah R, Brice P et al (2019) PET-adapted treatment for newly diagnosed advanced Hodgkin lymphoma (AHL2011): a randomised, multicentre, non-inferiority, phase 3 study. Lancet Oncol 20:202–215 CrossRef Casasnovas RO, Bouabdallah R, Brice P et al (2019) PET-adapted treatment for newly diagnosed advanced Hodgkin lymphoma (AHL2011): a randomised, multicentre, non-inferiority, phase 3 study. Lancet Oncol 20:202–215 CrossRef
9.
Zurück zum Zitat Connors JM, Jurczak W, Straus DJ et al (2018) Brentuximab Vedotin with chemotherapy for stage III or IV Hodgkin’s lymphoma. N Engl J Med 378:331–344 CrossRef Connors JM, Jurczak W, Straus DJ et al (2018) Brentuximab Vedotin with chemotherapy for stage III or IV Hodgkin’s lymphoma. N Engl J Med 378:331–344 CrossRef
10.
Zurück zum Zitat Damaschin C, Goergen H, Kreissl S et al (2022) Brentuximab vedotin-containing escalated BEACOPP variants for newly diagnosed advanced-stage classical Hodgkin lymphoma: follow-up analysis of a randomized phase II study from the German Hodgkin study group. Leukemia 36:580–582 CrossRef Damaschin C, Goergen H, Kreissl S et al (2022) Brentuximab vedotin-containing escalated BEACOPP variants for newly diagnosed advanced-stage classical Hodgkin lymphoma: follow-up analysis of a randomized phase II study from the German Hodgkin study group. Leukemia 36:580–582 CrossRef
11.
Zurück zum Zitat Demeestere I, Racape J, Dechene J et al (2021) Gonadal function recovery in patients with advanced Hodgkin lymphoma treated with a PET-adapted regimen: prospective analysis of a randomized phase III trial (AHL2011). J Clin Oncol 39:3251–3260 CrossRef Demeestere I, Racape J, Dechene J et al (2021) Gonadal function recovery in patients with advanced Hodgkin lymphoma treated with a PET-adapted regimen: prospective analysis of a randomized phase III trial (AHL2011). J Clin Oncol 39:3251–3260 CrossRef
12.
Zurück zum Zitat Eichenauer DA, Kreissl S, Buhnen I et al (2021) PET-2-guided escalated BEACOPP for advanced nodular lymphocyte-predominant Hodgkin lymphoma: a subgroup analysis of the randomized German Hodgkin study group HD18 study. Ann Oncol 32:807–810 CrossRef Eichenauer DA, Kreissl S, Buhnen I et al (2021) PET-2-guided escalated BEACOPP for advanced nodular lymphocyte-predominant Hodgkin lymphoma: a subgroup analysis of the randomized German Hodgkin study group HD18 study. Ann Oncol 32:807–810 CrossRef
13.
Zurück zum Zitat Eichenauer DA, Plutschow A, Kreissl S et al (2017) Incorporation of brentuximab vedotin into first-line treatment of advanced classical Hodgkin’s lymphoma: final analysis of a phase 2 randomised trial by the German Hodgkin study group. Lancet Oncol 18:1680–1687 CrossRef Eichenauer DA, Plutschow A, Kreissl S et al (2017) Incorporation of brentuximab vedotin into first-line treatment of advanced classical Hodgkin’s lymphoma: final analysis of a phase 2 randomised trial by the German Hodgkin study group. Lancet Oncol 18:1680–1687 CrossRef
14.
Zurück zum Zitat Engert A, Haverkamp H, Kobe C et al (2012) 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. Lancet 379:1791–1799 CrossRef Engert A, Haverkamp H, Kobe C et al (2012) 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. Lancet 379:1791–1799 CrossRef
15.
Zurück zum Zitat Gafter-Gvili A, Fraser A, Paul M et al (2012) Antibiotic prophylaxis for bacterial infections in afebrile neutropenic patients following chemotherapy. Cochrane Database Syst Rev 1:CD4386 PubMed Gafter-Gvili A, Fraser A, Paul M et al (2012) Antibiotic prophylaxis for bacterial infections in afebrile neutropenic patients following chemotherapy. Cochrane Database Syst Rev 1:CD4386 PubMed
16.
Zurück zum Zitat Gallamini A, Rossi A, Patti C et al (2020) Consolidation radiotherapy could be safely omitted in advanced Hodgkin lymphoma with large nodal mass in complete metabolic response after ABVD: final analysis of the randomized GITIL/FIL HD0607 trial. J Clin Oncol 38:3905–3913 CrossRef Gallamini A, Rossi A, Patti C et al (2020) Consolidation radiotherapy could be safely omitted in advanced Hodgkin lymphoma with large nodal mass in complete metabolic response after ABVD: final analysis of the randomized GITIL/FIL HD0607 trial. J Clin Oncol 38:3905–3913 CrossRef
17.
Zurück zum Zitat Gallamini A, Tarella C, Viviani S et al (2018) Early chemotherapy intensification with escalated BEACOPP in patients with advanced-stage Hodgkin lymphoma with a positive interim positron emission tomography/computed tomography scan after two ABVD cycles: long-term results of the GITIL/FIL HD 0607 trial. J Clin Oncol 36:454–462 CrossRef Gallamini A, Tarella C, Viviani S et al (2018) Early chemotherapy intensification with escalated BEACOPP in patients with advanced-stage Hodgkin lymphoma with a positive interim positron emission tomography/computed tomography scan after two ABVD cycles: long-term results of the GITIL/FIL HD 0607 trial. J Clin Oncol 36:454–462 CrossRef
18.
Zurück zum Zitat Hentrich M, Berger M, Wyen C et al (2012) Stage-adapted treatment of HIV-associated Hodgkin lymphoma: results of a prospective multicenter study. J Clin Oncol 30:4117–4123 CrossRef Hentrich M, Berger M, Wyen C et al (2012) Stage-adapted treatment of HIV-associated Hodgkin lymphoma: results of a prospective multicenter study. J Clin Oncol 30:4117–4123 CrossRef
19.
Zurück zum Zitat Hughes WT, Rivera GK, Schell MJ et al (1987) Successful intermittent chemoprophylaxis for Pneumocystis carinii pneumonitis. N Engl J Med 316:1627–1632 CrossRef Hughes WT, Rivera GK, Schell MJ et al (1987) Successful intermittent chemoprophylaxis for Pneumocystis carinii pneumonitis. N Engl J Med 316:1627–1632 CrossRef
20.
Zurück zum Zitat Johnson P, Federico M, Kirkwood A et al (2016) Adapted treatment guided by interim PET-CT scan in advanced Hodgkin’s lymphoma. N Engl J Med 374:2419–2429 CrossRef Johnson P, Federico M, Kirkwood A et al (2016) Adapted treatment guided by interim PET-CT scan in advanced Hodgkin’s lymphoma. N Engl J Med 374:2419–2429 CrossRef
21.
Zurück zum Zitat Kreissl S, Goergen H, Buehnen I et al (2021) PET-guided eBEACOPP treatment of advanced-stage Hodgkin lymphoma (HD18): follow-up analysis of an international, open-label, randomised, phase 3 trial. Lancet Haematol 8:e398–e409 CrossRef Kreissl S, Goergen H, Buehnen I et al (2021) PET-guided eBEACOPP treatment of advanced-stage Hodgkin lymphoma (HD18): follow-up analysis of an international, open-label, randomised, phase 3 trial. Lancet Haematol 8:e398–e409 CrossRef
22.
Zurück zum Zitat Kriz J, Reinartz G, Dietlein M et al (2015) Relapse analysis of irradiated patients within the HD15 trial of the German Hodgkin study group. Int J Radiat Oncol Biol Phys 92:46–53 CrossRef Kriz J, Reinartz G, Dietlein M et al (2015) Relapse analysis of irradiated patients within the HD15 trial of the German Hodgkin study group. Int J Radiat Oncol Biol Phys 92:46–53 CrossRef
23.
Zurück zum Zitat Kuruvilla J, Ramchandren R, Santoro A et al (2021) 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 22:512–524 CrossRef Kuruvilla J, Ramchandren R, Santoro A et al (2021) 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 22:512–524 CrossRef
24.
Zurück zum Zitat Lynch RC, Ujjani CS, Poh C et al (2021) Concurrent Pembrolizumab with AVD for Untreated Classical Hodgkin Lymphoma. Blood 138:233–233 CrossRef Lynch RC, Ujjani CS, Poh C et al (2021) Concurrent Pembrolizumab with AVD for Untreated Classical Hodgkin Lymphoma. Blood 138:233–233 CrossRef
25.
Zurück zum Zitat Montoto S, Shaw K, Okosun J et al (2012) HIV status does not influence outcome in patients with classical Hodgkin lymphoma treated with chemotherapy using doxorubicin, bleomycin, vinblastine, and dacarbazine in the highly active antiretroviral therapy era. J Clin Oncol 30:4111–4116 CrossRef Montoto S, Shaw K, Okosun J et al (2012) HIV status does not influence outcome in patients with classical Hodgkin lymphoma treated with chemotherapy using doxorubicin, bleomycin, vinblastine, and dacarbazine in the highly active antiretroviral therapy era. J Clin Oncol 30:4111–4116 CrossRef
26.
Zurück zum Zitat Skoetz N, Trelle S, Rancea M et al (2013) Effect of initial treatment strategy on survival of patients with advanced-stage Hodgkin’s lymphoma: a systematic review and network meta-analysis. Lancet Oncol 14:943–952 CrossRef Skoetz N, Trelle S, Rancea M et al (2013) Effect of initial treatment strategy on survival of patients with advanced-stage Hodgkin’s lymphoma: a systematic review and network meta-analysis. Lancet Oncol 14:943–952 CrossRef
27.
Zurück zum Zitat Skoetz N, Will A, Monsef I et al (2017) Comparison of first-line chemotherapy including escalated BEACOPP versus chemotherapy including ABVD for people with early unfavourable or advanced stage Hodgkin lymphoma. Cochrane Database Syst Rev 5:CD7941 PubMed Skoetz N, Will A, Monsef I et al (2017) Comparison of first-line chemotherapy including escalated BEACOPP versus chemotherapy including ABVD for people with early unfavourable or advanced stage Hodgkin lymphoma. Cochrane Database Syst Rev 5:CD7941 PubMed
28.
Zurück zum Zitat Specht L, Yahalom J, Illidge T et al (2014) Modern radiation therapy for Hodgkin lymphoma: field and dose guidelines from the international lymphoma radiation oncology group (ILROG). Int J Radiat Oncol Biol Phys 89:854–862 CrossRef Specht L, Yahalom J, Illidge T et al (2014) Modern radiation therapy for Hodgkin lymphoma: field and dose guidelines from the international lymphoma radiation oncology group (ILROG). Int J Radiat Oncol Biol Phys 89:854–862 CrossRef
30.
Zurück zum Zitat Stephens DM, Li H, Schoder H et al (2019) Five-year follow-up of SWOG S0816: limitations and values of a PET-adapted approach with stage III/IV Hodgkin lymphoma. Blood 134:1238–1246 CrossRef Stephens DM, Li H, Schoder H et al (2019) Five-year follow-up of SWOG S0816: limitations and values of a PET-adapted approach with stage III/IV Hodgkin lymphoma. Blood 134:1238–1246 CrossRef
31.
Zurück zum Zitat Straus DJ, Dlugosz-Danecka M, Connors JM et al (2021) Brentuximab vedotin with chemotherapy for stage III or IV classical Hodgkin lymphoma (ECHELON-1): 5‑year update of an international, open-label, randomised, phase 3 trial. Lancet Haematol 8:e410–e421 CrossRef Straus DJ, Dlugosz-Danecka M, Connors JM et al (2021) Brentuximab vedotin with chemotherapy for stage III or IV classical Hodgkin lymphoma (ECHELON-1): 5‑year update of an international, open-label, randomised, phase 3 trial. Lancet Haematol 8:e410–e421 CrossRef
32.
Zurück zum Zitat Viviani S, Zinzani PL, Rambaldi A et al (2011) ABVD versus BEACOPP for Hodgkin’s lymphoma when high-dose salvage is planned. N Engl J Med 365:203–212 CrossRef Viviani S, Zinzani PL, Rambaldi A et al (2011) ABVD versus BEACOPP for Hodgkin’s lymphoma when high-dose salvage is planned. N Engl J Med 365:203–212 CrossRef
33.
Zurück zum Zitat Von Tresckow B, Kreissl S, Goergen H et al (2018) Intensive treatment strategies in advanced-stage Hodgkin’s lymphoma (HD9 and HD12): analysis of long-term survival in two randomised trials. Lancet Haematol 5:e462–e473 CrossRef Von Tresckow B, Kreissl S, Goergen H et al (2018) Intensive treatment strategies in advanced-stage Hodgkin’s lymphoma (HD9 and HD12): analysis of long-term survival in two randomised trials. Lancet Haematol 5:e462–e473 CrossRef
34.
Zurück zum Zitat Younes A, Santoro A, Shipp M et al (2016) Nivolumab for classical Hodgkin’s lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin: a multicentre, multicohort, single-arm phase 2 trial. Lancet Oncol 17:1283–1294 CrossRef Younes A, Santoro A, Shipp M et al (2016) Nivolumab for classical Hodgkin’s lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin: a multicentre, multicohort, single-arm phase 2 trial. Lancet Oncol 17:1283–1294 CrossRef
Metadaten
Titel
Das Hodgkin-Lymphom in fortgeschrittenen Stadien
verfasst von
Dr. med. J. Ferdinandus
M. Oertel
D. A. Eichenauer
J. Meissner
A. Engert
P. Borchmann
Publikationsdatum
01.06.2022
Verlag
Springer Medizin
Erschienen in
Die Onkologie / Ausgabe 10/2022
Print ISSN: 2731-7226
Elektronische ISSN: 2731-7234
DOI
https://doi.org/10.1007/s00761-022-01186-9