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Neue Entwicklungen in der Therapie des fortgeschrittenen Hodgkin-Lymphoms

New developments in the treatment of advanced Hodgkin’s lymphoma

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Zusammenfassung

Hintergrund

Das Gesamtüberleben von Patienten mit fortgeschrittenem Hodgkin-Lymphom (HL) unter dem aktuellen Standard der German Hodgkin Study Group (GHSG) „6 Zyklen BEACOPPeskaliert + Bestrahlung PET-positiver Reste ≥ 2,5 cm“ liegt bei 95 %. Großer Bedarf besteht nach wie vor in der Optimierung der Primärtherapie hinsichtlich der therapieassoziierten Akut- und Langzeittoxizitäten. Langfristiges Ziel ist die Reduktion von Nebenwirkungen bei gleichbleibend gutem Therapieerfolg.

Ziel

Evidenzbasierte Zusammenfassung des aktuellen Therapiestandards sowie neuer Entwicklungen in der Therapie des fortgeschrittenen HL.

Material und Methode

Mittels systematischer und manueller Literaturrecherche wurden relevante Publikationen sowie im Rahmen derzeit laufender Studien getestete neue Therapieansätze zusammengefasst.

Ergebnisse

Aktuelle Vergleiche von BEACOPPeskaliert und ABVD zeigen einen hoch signifikanten und klinisch bedeutenden Überlebensvorteil für BEACOPPeskaliert sowohl im Sinne des progressionsfreien Überlebens (PFS, Vorteil um 20 %) als auch des Gesamtüberlebens (OS, Vorteil um 10 %). In Kombination mit begleitenden Maßnahmen wie einer obligaten Dexamethason-Vorphase für Patienten > 40 Jahre und einer Antibiotika-Prophylaxe in der Aplasiephase stellt dieser Standard eine sichere Therapie dar. Dementsprechend liegt die aktuell größte Herausforderung in der Reduktion therapieassoziierter Nebenwirkungen bei gleichbleibend gutem Therapieerfolg. Hierzu testet die laufende HD18-Studie der GHSG die Reduktion der Therapie von 6 auf 4 Zyklen BEACOPPeskaliert für Patienten mit gutem, PET-definiertem, frühem Therapieansprechen. Eine weitere Strategie zur Verbesserung der Nebenwirkungsrate stellt die Implementierung neuer, zielgerichteter Substanzen wie Brentuximab Vedotin in die First-Line-Therapie dar. Dieser Ansatz der „targeted therapy“ wird aktuell in der Targeted-BEACOPP-Studie der GHSG mit zwei unterschiedlich stark modifizierten BEACOPP-Varianten in Kombination mit Brentuximab Vedotin untersucht.

Schlussfolgerungen

Langfristiges Ziel in der Behandlung des HL ist die Implementierung zielgerichteter Substanzen in die Primätherapie. Seit 2012 ist Brentuximab Vedotin europaweit für die Behandlung des rezidivierten bzw. refraktären HL zugelassen. Die laufende Targeted-BEACOPP-Studie testet aktuell die Effektivität und Verträglichkeit zweier unterschiedlich stark modifizierter BACOPP-Varianten in Kombination mit Brentuximab Vedotin. Ziel ist der Erhalt der Effektivität des klassichen BEACOPP-Schemas bei Reduktion der therapieassoziierten Nebenwirkungen.

Abstract

Context

With the current standard of care of the German Hodgkin Study Group (GHSG) consisting of 6 cycles of the BEACOPPescalated regimen and radiotherapy of residual lymphomas ≥ 2.5 cm, the overall survival (OS) of patients with advanced Hodgkin’s lymphoma (HL) is 95 %. However, minimizing acute and late toxicities without compromising the tumor-specific outcome of patients is the major goal of current clinical research. Defining the correct balance between efficacy and toxicity remains the most important challenge in treatment of HL.

Objective

This article presents an evidence-based systematic review of the current status of therapy as well as new developments in the treatment of advanced HL.

Material and methods

A systematic literature search was carried out and relevant publications as well as new developments in the treatment of advanced HL tested in current trials are summarized.

Results

Recent comparisons of the BEACOPPescalated and ABVD regimens showed a substantial benefit of BEACOPPescalated in terms of progression-free survival (PFS) and OS. In combination with supportive treatment measures, such as obligatory prephase treatment with dexamethasone for patients older than 40 years and prophylactic antibiotic treatment during the time of aplasia, 6 cycles of BEACOPPescalated can be considered a safe and feasible therapy. Thus, minimizing acute and late toxicities without compromising the tumor-specific outcome of patients is the major goal of current clinical research. The recruiting GHSG HD18 trial investigates the reduction from 6 to 4 cycles of BEACOPPescalated for patients with good, early tumor response as defined by positron emission tomography (PET). Another strategy might be the implementation of targeted drugs into the first-line therapy. This approach is currently being evaluated in the GHSG targeted BEACOPP study (NCT01569204) with the implementation of brentuximab vedotin into two modified BEACOPP regimens.

Conclusions

The major goal in the treatment of advanced HL is the implementation of targeted drugs into the first-line therapy. Targeted drugs might replace unspecific cytotoxic drugs, which cause systemic toxicity. Brentuximab vedotin was approved for use in Europe in November 2012 for the treatment of relapsed or refractory HL and is currently being investigated in combination with two modified escalated BEACOPP regimens in advanced stage HL patients in the targeted BEACOPP trial. Hopefully, these new combinations will improve the current standard of care in the treatment of HL regarding both efficacy and tolerability.

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Literatur

  1. Engert A 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(9828):1791–1799

    Article  CAS  PubMed  Google Scholar 

  2. Connors JM (2011) Hodgkin’s lymphoma – the great teacher. N Engl J Med 365(3):264–265

    Article  CAS  PubMed  Google Scholar 

  3. Diehl V et al (2003) Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin’s disease. N Engl J Med 348(24):2386–2395

    Article  CAS  PubMed  Google Scholar 

  4. Skoetz N et al (2013) First line treatment of advanced stage Hodgkin lymphoma with six cycles of BEACOP pescalated results in superior overall survival compared to ABVD: results of a network meta-analysis including 10,011 patients. Lancet Oncol (accepted, 2013)

  5. Wongso D et al (2012) Treatment-related mortality in patients with advanced-stage Hodgkin lymphoma: an analysis of the German Hodgkin Study Group (GHSG). Haematologica abs 1111:457.(17)

    Google Scholar 

  6. Behringer K et al (2013) Gonadal function and fertility in survivors after Hodgkin lymphoma treatment within the German Hodgkin Study Group HD13 to HD15 trials. J Clin Oncol 31(2):231–239

    Article  CAS  PubMed  Google Scholar 

  7. Behringer K et al (2012) Fertility and gonadal function in female survivors after treatment of early unfavorable Hodgkin lymphoma (HL) within the German Hodgkin Study Group HD14 trial. Ann Oncol 23(7):1818–1825

    Article  CAS  PubMed  Google Scholar 

  8. Gordon LI et al (2013) Randomized phase III trial of ABVD versus Stanford V with or without radiation therapy in locally extensive and advanced-stage Hodgkin lymphoma: an intergroup study coordinated by the Eastern Cooperative Oncology Group (E2496). J Clin Oncol 31(6):684–691

    Article  PubMed Central  PubMed  Google Scholar 

  9. Hoskin PJ (2009) 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 27(32):5390–5396

    Article  PubMed  Google Scholar 

  10. Viviani S et al (2011) ABVD versus BEACOPP for Hodgkin’s lymphoma when high-dose salvage is planned. N Engl J Med 365(3):203–212

    Article  CAS  PubMed  Google Scholar 

  11. Carde P, Mounier N (2012) ABVD (8 cycles) versus BEACOPP (4 escalated cycles =>(4 baseline) in stage III–IV high-risk Hodgkin lymphoma (HL): first results of EORTC 20012 intergroup randomized phase III clinical trial. in annual meeting of the Amercian Society of Clinical Oncology. Chicago, Il

  12. Mounier N et al (2013) ABVD (eight cycles) versus BEACOPP (4 escalated cycles to 4 baseline) in stages III–IV low risk Hodgkin lymphoma (IPS 0–2): final results of the LYSA H34 trial. Hematol Oncol 31((Suppl 1) abs 127):96–150

    Google Scholar 

  13. Federico M et al (2009) ABVD compared with BEACOPP compared with CEC for the initial treatment of patients with advanced Hodgkin’s lymphoma: results from the HD2000 Gruppo Italiano per lo Studio dei Linfomi Trial. J Clin Oncol 27(5):805–811

    Article  PubMed  Google Scholar 

  14. Borchmann P et al (2012) First line treatment of advanced stage Hodgkin lymphoma with six cycles of BEACOPPescalated results in superior overall survival compared to ABVD: results of a network meta-analysis including 10,011 patients. 54th ASH Annual Meeting Abstracts

  15. Johnson P et al (2013) Response rates and toxicity of response-adapted therapy in advanced Hodgkin Lymphoma: Initial results from the international RATHL study. Haematologica 98(s2):9

    Article  Google Scholar 

  16. Younes A et al (2010) Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. N Engl J Med 363(19):1812–1821

    Article  CAS  PubMed  Google Scholar 

  17. Okeley NM et al (2010) Intracellular activation of SGN-35, a potent anti-CD30 antibody-drug conjugate. Clin Cancer Res 16(3):888–897

    Article  CAS  PubMed  Google Scholar 

  18. Younes A et al (2012) Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin’s lymphoma. J Clin Oncol 30(18):2183–2189

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Ansell SM et al (2012) Frontline therapy with brentuximab vedotin combined with ABVD or AVD in patients with newly diagnosed advanced stage Hodgkin Lymphoma. ASH Annual Meeting Abstracts 120(21):798

    Google Scholar 

  20. Borchmann P et al (2012) First line treatment of advanced stage Hodgkin lymphoma with six cycles of BEACOPPescalated results in superior overall survival compared to ABVD: results of a network meta-analysis including 10,011 Patients. 54th ASH Annual Meeting Abstracts.

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Einhaltung ethischer Richtlinien

Interessenkonflikt. Frau Kreissl: kein Interessenkonflikt. Herr Prof. Borchmann: Forschungsförderung durch TAKEDA. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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Authors and Affiliations

  1. Klinik I für Innere Medizin, Universitätsklinik Köln, German Hodgkin Study Group, Kerpener Straße 62, 50924, Köln, Deutschland

    S. Kreissl, D. Eichenauer & P. Borchmann

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  1. S. Kreissl
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  2. D. Eichenauer
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  3. P. Borchmann
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Correspondence to S. Kreissl.

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Kreissl, S., Eichenauer, D. & Borchmann, P. Neue Entwicklungen in der Therapie des fortgeschrittenen Hodgkin-Lymphoms. Onkologe 20, 457–463 (2014). https://doi.org/10.1007/s00761-013-2637-3

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  • DOI: https://doi.org/10.1007/s00761-013-2637-3

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