Skip to main content
SpringerLink
Log in

Long-term follow-up of rituximab plus first-line mitoxantrone, chlorambucil, prednisolone and interferon-alpha as maintenance therapy in follicular lymphoma

  • Original Article – Clinical Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

The randomised, controlled OSHO#39 study showed promising results using first-line mitoxantrone, chlorambucil and prednisolone (MCP) chemotherapy plus rituximab in patients with advanced symptomatic follicular lymphoma (FL) in need of therapy. The aim of this long-term follow-up was to investigate whether clinical benefits are maintained after up to 9 years of observation.

Methods

Following the 4-year follow-up of OSHO#39, 77 FL patients who received rituximab plus MCP (R-MCP) and 52 patients who received MCP (129 patients alive and not previously censored in total) were followed for 5 additional years in this prospective, non-interventional, observational study. For the efficacy analysis, data were jointly analysed with OSHO#39 data (FL intention-to-treat population: 105 patients R-MCP, 96 MCP). Patients not included in the 5-year follow-up were censored.

Results

For surviving patients, median follow-up was 102 months (R-MCP) and 87 months (MCP). Although median overall survival (OS) was not yet reached, OS was longer for patients with R-MCP compared with MCP (p = 0.0057), with 8-year-survival rates of 76.1 versus 55.9 %. Further time-to-event data were substantially longer for the R-MCP group than for MCP alone: median progression-free survival (PFS) was 93.4 versus 34.9 months, and median event-free survival (EFS) 89.6 versus 26.5 months. Unplanned subanalyses of patients with and without interferon maintenance showed improved PFS and EFS without an impact on OS.

Conclusions

The addition of rituximab to first-line MCP chemotherapy improves clinical outcomes in advanced FL patients and translates into long-term OS benefits. R-MCP remains a promising standard option for this patient group.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Buske C et al (2008) Rituximab in combination with CHOP in patients with follicular lymphoma: analysis of treatment outcome of 552 patients treated in a randomized trial of the German Low Grade Lymphoma Study Group (GLSG) after a follow up of 58 months Blood (ASH Annual Meeting Abstracts) 112:Abstract 2599

  • Bachy E et al (2013) Long-term follow up of the FL2000 study comparing CHVP-interferon to CHVP-interferon plus rituximab in follicular lymphoma. Haematologica 98:1107–1114. doi:10.3324/haematol.2012.082412

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Buske C, Herold M, Willenbacher W, Dreyling M (2012) Follikuläres Lymphom (FL). DGHO-Onkopedia-Leitlinie. http://www.dgho-onkopedia.de/de/onkopedia/leitlinien/follikulaeres-lymphom#medikamentose-tumortherapie-protokolle. Zugriff am 2.9.2013

  • Dreyling M, Ghielmini M, Marcus R, Salles G, Vitolo U, Group EGW (2011) Newly diagnosed and relapsed follicular lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 22(Suppl 6):vi59–vi63. doi:10.1093/annonc/mdr388

    PubMed  Google Scholar 

  • Forstpointner R et al (2004) The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood 104:3064–3071. doi:10.1182/blood-2004-04-1323

    Article  CAS  PubMed  Google Scholar 

  • Griffin MM, Morley N (2013) Rituximab in the treatment of non-Hodgkin’s lymphoma—a critical evaluation of randomized controlled trials. Expert Opin Biol Ther 13:803–811. doi:10.1517/14712598.2013.786698

    Article  CAS  PubMed  Google Scholar 

  • Groves FD, Linet MS, Travis LB, Devesa SS (2000) Cancer surveillance series: non-Hodgkin’s lymphoma incidence by histologic subtype in the United States from 1978 through. J Natl Cancer Inst 92:1240–1251

    Article  CAS  PubMed  Google Scholar 

  • Herold M et al (2007) Rituximab added to first-line mitoxantrone, chlorambucil, and prednisolone chemotherapy followed by interferon maintenance prolongs survival in patients with advanced follicular lymphoma: an East German Study Group Hematology and Oncology Study. J Clin Oncol 25:1986–1992. doi:10.1200/JCO.2006.06.4618

    Article  CAS  PubMed  Google Scholar 

  • Hiddemann W et al (2005) Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood 106:3725–3732. doi:10.1182/blood-2005-01-0016

    Article  CAS  PubMed  Google Scholar 

  • Li ZM, Ghielmini M, Moccia AA (2013) Managing newly diagnosed follicular lymphoma: state of the art and future perspectives. Expert Rev Anticancer Ther 13:313–325. doi:10.1586/era.13.6

    Article  CAS  PubMed  Google Scholar 

  • Lister TA (2005) Improved survival for patients with follicular lymphoma. J Clin Oncol 23:4830–4831. doi:10.1200/JCO.2005.03.911

    Article  PubMed  Google Scholar 

  • Liu Q et al (2006) Improvement of overall and failure-free survival in stage IV follicular lymphoma: 25 years of treatment experience at The University of Texas M.D. Anderson Cancer Center. J Clin Oncol 24:1582–1589. doi:10.1200/JCO.2005.03.3696

    Article  PubMed  Google Scholar 

  • Luminari S, Bellei M, Biasoli I, Federico M (2012) Follicular lymphoma—treatment and prognostic factors. Rev Bras Hematol Hemoter 34:54–59. doi:10.5581/1516-8484.20120015

    Article  PubMed Central  PubMed  Google Scholar 

  • Marcus R et al (2008) Phase III study of R-CVP compared with cyclophosphamide, vincristine, and prednisone alone in patients with previously untreated advanced follicular lymphoma. J Clin Oncol 26:4579–4586. doi:10.1200/JCO.2007.13.5376

    Article  CAS  PubMed  Google Scholar 

  • Morton LM, Wang SS, Devesa SS, Hartge P, Weisenburger DD, Linet MS (2006) Lymphoma incidence patterns by WHO subtype in the United States, 1992–2001. Blood 107:265–276. doi:10.1182/blood-2005-06-2508

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Rohatiner AZ et al (2005) Meta-analysis to evaluate the role of interferon in follicular lymphoma. J Clin Oncol 23:2215–2223. doi:10.1200/JCO.2005.06.146

    Article  CAS  PubMed  Google Scholar 

  • Rummel MJ et al (2013) Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Lancet 381:1203–1210. doi:10.1016/S0140-6736(12)61763-2

    Article  CAS  PubMed  Google Scholar 

  • Salles G et al (2008) Rituximab combined with chemotherapy and interferon in follicular lymphoma patients: results of the GELA-GOELAMS FL2000 study. Blood 112:4824–4831. doi:10.1182/blood-2008-04-153189

    Article  CAS  PubMed  Google Scholar 

  • Salles G et al (2011) Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet 377:42–51. doi:10.1016/S0140-6736(10)62175-7

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank the members of the East German Study Group (OSHO) for their commitment: Dirk Behringer, Augusta-Kranken-Anstalt GmbH, Bochum; Mathias Hänel, Klinikum Chemnitz GmbH, Chemnitz; Ulrich von Grünhagen, Onkologische Schwerpunktpraxis, Cottbus; Thomas Illmer, Onkologische Schwerpunktpraxis, Dresden; Henning Eschenburg, Onkologische Schwerpunktpraxis, Güstrow; Robert Rohrberg, onkomedic GmbH, Halle; Hans-Heinrich Wolf, Martin-Luther-Universität Halle-Wittenberg, Halle; Andreas Hochhaus, Friedrich-Schiller-Universität, Jena; Sabine Hahnfeld, Onkologische Schwerpunktpraxis, Jena; Franz Albert Hoffmann, Onkologische Schwerpunktpraxis, Leipzig; Dietger Niederwieser, Kliniken der Universität Leipzig, Leipzig; Matthias Wußling, Onkologische Praxis, Nordhausen; Lars Fischer, Charité, Berlin; Wolfgang Stein, Klinikum Frankfurt (Oder) GmbH, Frankfurt (Oder); Karsten Ridwelski, Städtisches Klinikum Magdeburg, Magdeburg; Andreas Neubauer, Universitätsklinikum Marburg, Marburg; Norbert Grobe, Klinikum Neubrandenburg, Neubrandenburg; Detlev Hähling, HELIOS Kliniken Schwerin, Schwerin. Statistical analyses were conducted by the contract research organisation Ecron Acunova GmbH, Frankfurt, Germany, who also checked the documentation of serious adverse drug reactions for completeness and plausibility. This research was funded by Roche Pharma AG, Grenzach-Whylen, Germany. Medical writing assistance was provided by Physicians World Europe, Mannheim, Germany, supported by Roche Pharma AG, Grenzach-Wyhlen, Germany.

Conflict of interest

Michael Herold: Honoraria, advisory board, research support from Roche Pharma AG. Christian Scholz: Roche speaker fees, advisory board, travel support. Frank Rothmann: No conflict of interest. Carsten Hirt: Travel and research funding from Roche Pharma AG. Volker Lakner: No conflict of interest. Ralph Naumann: No conflict of interest.

Ethical standard

The observational plan was reviewed by the Landesärztekammer Thüringen local ethics committee. The study has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All patients gave their informed consent prior to their inclusion in the study.

Author information

Authors and Affiliations

  1. Onkologisches Zentrum, HELIOS-Klinikum Erfurt, Nordhäuserstr. 74, 99089, Erfurt, Germany

    Michael Herold

  2. Klinik für Innere Medizin, Hämatologie und Onkologie, Vivantes Klinikum Am Urban, Dieffenbachstrasse 1, 10967, Berlin, Germany

    Christian W. Scholz

  3. Klinik für Hämatologie, Onkologie und Palliativmedizin, Klinikum Ernst von Bergmann, Charlottenstraße 72, 14467, Potsdam, Germany

    Frank Rothmann

  4. Klinik und Poliklinik für Innere Medizin C, Hämatologie und Onkologie, Universitätsmedizin Greifswald, Sauerbruchstraße, 17475, Greifswald, Germany

    Carsten Hirt

  5. Onkologische Gemeinschaftspraxis, Wismarsche Str. 32, 18057, Rostock, Germany

    Volker Lakner

  6. Zentrum für Innere Medizin, Gemeinschaftsklinikum Mittelrhein, Johannes-Müller-Str. 7, 56068, Koblenz, Germany

    Ralph Naumann

Authors
  1. Michael Herold
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christian W. Scholz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Frank Rothmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Carsten Hirt
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Volker Lakner
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ralph Naumann
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael Herold.

Additional information

For the East German Study Group (OSHO).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Herold, M., Scholz, C.W., Rothmann, F. et al. Long-term follow-up of rituximab plus first-line mitoxantrone, chlorambucil, prednisolone and interferon-alpha as maintenance therapy in follicular lymphoma. J Cancer Res Clin Oncol 141, 1689–1695 (2015). https://doi.org/10.1007/s00432-015-1963-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-015-1963-9

Keywords

Search

Navigation