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Das Hodgkin-Lymphom in fortgeschrittenen Stadien

Advanced-stage Hodgkin lymphoma

  • Leitthema
  • Published:
Die Onkologie Aims and scope

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.

Abstract

Background

In recent years, positron emission tomography (PET)-adapted protocols and new agents such as brentuximab vedotin are increasingly used as part of first-line protocols of advanced-stage Hodgkin lymphoma (HL).

Objectives

This manuscript reviews guideline-based therapy and available trial data in advanced-stage HL.

Materials and methods

This is a narrative review.

Results

The German HL guideline recommends interim PET2-guided (PET after 2 cycles) chemotherapy using 4 cycles of eBEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone) for PET2-negative patients up to 60 years of age with advanced HL and 6 cycles eBEACOPP for PET2-positive patients. Furthermore, patients with PET-positive residual lymphoma should receive consolidation radiotherapy with 30 Gy. This is based on effective tumor control and short duration of therapy of 3 months in most patients. For elderly patients, treatment with 2 cycles of ABVD (adriamycin, bleomycin, vinblastine and dacarbazine) followed by 4 cycles of AVD and irradiation of PET-positive residuals is recommended.

Conclusions

Advanced-stage HL is curable in more than 90% of cases. The goal of current scientific efforts is to reduce toxicity while maintaining efficacy by including immune checkpoint inhibitors.

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Literatur

  1. 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

    Article  CAS  Google Scholar 

  2. 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

    Article  CAS  Google Scholar 

  3. 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

    Article  Google Scholar 

  4. 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

    Article  Google Scholar 

  5. 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

    Article  CAS  Google Scholar 

  6. 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

    Article  CAS  Google Scholar 

  7. 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

    Article  Google Scholar 

  8. Casasnovas RO, Bouabdallah R, Brice P et al (2022) Positron emission tomography-driven strategy in advanced Hodgkin lymphoma: prolonged follow-up of the AHL2011 phase III lymphoma study association study. J Clin Oncol. https://doi.org/10.1200/JCO.21.01777

    Article  PubMed  Google Scholar 

  9. 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

    Article  CAS  Google Scholar 

  10. 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

    Article  CAS  Google Scholar 

  11. 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

    Article  CAS  Google Scholar 

  12. 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

    Article  CAS  Google Scholar 

  13. 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

    Article  CAS  Google Scholar 

  14. 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

    Article  CAS  Google Scholar 

  15. 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  Google Scholar 

  16. 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

    Article  CAS  Google Scholar 

  17. 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

    Article  CAS  Google Scholar 

  18. 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

    Article  Google Scholar 

  19. Hughes WT, Rivera GK, Schell MJ et al (1987) Successful intermittent chemoprophylaxis for Pneumocystis carinii pneumonitis. N Engl J Med 316:1627–1632

    Article  CAS  Google Scholar 

  20. 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

    Article  Google Scholar 

  21. 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

    Article  Google Scholar 

  22. 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

    Article  Google Scholar 

  23. 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

    Article  CAS  Google Scholar 

  24. Lynch RC, Ujjani CS, Poh C et al (2021) Concurrent Pembrolizumab with AVD for Untreated Classical Hodgkin Lymphoma. Blood 138:233–233

    Article  Google Scholar 

  25. 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

    Article  Google Scholar 

  26. 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

    Article  Google Scholar 

  27. 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  Google Scholar 

  28. 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

    Article  Google Scholar 

  29. Spina M, Carbone A, Gloghini A et al (2011) Hodgkin’s Disease in Patients with HIV Infection. Adv Hematol. https://doi.org/10.1155/2011/402682

    Article  PubMed  Google Scholar 

  30. 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

    Article  Google Scholar 

  31. 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

    Article  Google Scholar 

  32. 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

    Article  CAS  Google Scholar 

  33. 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

    Article  Google Scholar 

  34. 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

    Article  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Deutsche Hodgkin Studiengruppe, Medizinische Fakultät und Universitätsklinikum Köln, Universität Köln, Köln, Deutschland

    J. Ferdinandus, D. A. Eichenauer, A. Engert & P. Borchmann

  2. Klinik I für Innere Medizin, Universitätsklinikum Köln, Kerpener Str. 62, 50937, Köln, Deutschland

    J. Ferdinandus, D. A. Eichenauer, A. Engert & P. Borchmann

  3. Klinik für Strahlentherapie – Radioonkologie, Universitätsklinikum Münster, Münster, Deutschland

    M. Oertel

  4. Medizinische Klinik V, Universitätsklinikum Heidelberg, Heidelberg, Deutschland

    J. Meissner

Authors
  1. J. Ferdinandus
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  2. M. Oertel
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  3. D. A. Eichenauer
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  4. J. Meissner
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  5. A. Engert
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  6. P. Borchmann
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Corresponding author

Correspondence to J. Ferdinandus.

Ethics declarations

Interessenkonflikt

M. Oertel verwaltet Gelder der Deutschen Krebshilfe zur Qualitätsanalyse der Radiotherapie in der HD16/17-Studie. J. Meissner gibt Reisekostenübernahmen durch MSD, BMS und Takeda an. A. Engert erklärt Beratertätigkeiten (AstraZeneca, Merck Sharpe & Dohme, Takeda, Tessa Pharma), Studienunterstützung (Bristol-Myers Squibb) und Vortragshonorare (AstraZeneca, Hexal AG, Innovent, Janssen, Takeda, TS Oncology). P. Borchmann erklärt Beratertätigkeiten (Takeda Oncology, Bristol-Myers Squibb, Merck Sharp & Dohme, Roche, Novartis, Amgen, Miltenyi Biotech), Vortragshonorare (Takeda Oncology, Novartis, Bristol-Myers Squibb, Roche, Merck Sharp & Dohme, Miltenyi Biotech, Incyte, Abbvie) und Studienunterstützung (Takeda Oncology, Roche, Novartis, Merck Sharp & Dohme, Amgen). J. Ferdinandus und D.A. Eichenauer geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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Ferdinandus, J., Oertel, M., Eichenauer, D.A. et al. Das Hodgkin-Lymphom in fortgeschrittenen Stadien. Onkologie 28, 889–900 (2022). https://doi.org/10.1007/s00761-022-01186-9

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  • DOI: https://doi.org/10.1007/s00761-022-01186-9

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