Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter to the Editor
  • Published:

Obinutuzumab as frontline treatment of chronic lymphocytic leukemia: updated results of the CLL11 study

Leukemia volume 29, pages 1602–1604 (2015)Cite this article

Subjects

Obinutuzumab is a novel glycoengineered, humanized, type II anti-CD20 antibody. In preclinical studies, obinutuzumab showed greater antileukemic activity than the type I and non-glycoengineered anti-CD20 antibodies rituximab and ofatumumab.1, 2, 3 Obinutuzumab recently became available for the treatment of patients with chronic lymphocytic leukemia (CLL). Approval of the antibody in this indication was based on primary results of the CLL11 study (NCT01010061), which compared obinutuzumab (also known as GA101) plus chlorambucil (G-Clb) with rituximab plus chlorambucil (R-Clb) and with chlorambucil alone (Clb) in patients with previously untreated CLL and comorbidities.4 In an analysis with a data cutoff in May 2013, G-Clb demonstrated superiority over R-Clb with regard to progression-free survival (PFS) and treatment response. The addition of obinutuzumab to Clb resulted in prolonged overall survival (OS) compared with treatment with Clb alone, whereas rituximab added to Clb compared with Clb alone did not result in a statistically significant OS benefit. There was also no difference in OS between G-Clb and R-Clb treatment at the time. As survival data can change with longer patient follow-up, we report here updated results on PFS and OS from an analysis with a data cutoff in April 2014.

Study methods were as previously published.4 In brief, 781 treatment-naive patients with CLL in need of therapy and with significant comorbidity burden were enrolled from April 2010 to July 2012 and randomly assigned for treatment with G-Clb, R-Clb or Clb alone. Diagnosis of CLL was according to the criteria of the International Workshop on Chronic Lymphocytic Leukemia.5 The comorbidity burden was assessed by the Cumulative Illness Rating Scale (CIRS) and by calculating creatinine clearance (CrCl) using the Cockcroft–Gault formula (with CIRS greater than 6 and/or CrCl of 30–69 ml/min used as eligibility criteria).6, 7 Obinutuzumab was infused at 1000 mg on days 1, 8 and 15 of cycle 1 and on day 1 of cycles 2–6 (each 28 days in duration). The first infusion of obinutuzumab was split over 2 days. Rituximab was administered at 375 and 500 mg/m2 body surface area on day 1 of cycle 1 and cycles 2–6, respectively. Clb was given orally at 0.5 mg/kg body weight on days 1 and 15 of cycles 1–6. PFS was the primary endpoint of the trial. Secondary endpoints included OS and time to next antileukemic treatment. Kaplan–Meier methodology and a two-sided log-rank test were used to estimate and compare survival times.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

References

  1. Patz M, Isaeva P, Forcob N, Muller B, Frenzel LP, Wendtner CM et al. Comparison of the in vitro effects of the anti-CD20 antibodies rituximab and GA101 on chronic lymphocytic leukaemia cells. Br J Haematol 2011; 152: 295–306.

    Article  CAS  Google Scholar 

  2. Mossner E, Brunker P, Moser S, Puntener U, Schmidt C, Herter S et al. Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cell-mediated B-cell cytotoxicity. Blood 2010; 115: 4393–4402.

    Article  CAS  Google Scholar 

  3. Herter S, Herting F, Mundigl O, Waldhauer I, Weinzierl T, Fauti T et al. Preclinical activity of the type II CD20 antibody GA101 (obinutuzumab) compared with rituximab and ofatumumab in vitro and in xenograft models. Mol Cancer Ther 2013; 12: 2031–2042.

    Article  CAS  Google Scholar 

  4. Goede V, Fischer K, Busch R, Engelke A, Eichhorst B, Wendtner CM et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med 2014; 370: 1101–1110.

    Article  CAS  Google Scholar 

  5. Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Dohner H et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood 2008; 111: 5446–5456.

    Article  CAS  Google Scholar 

  6. Parmelee PA, Thuras PD, Katz IR, Lawton MP . Validation of the Cumulative Illness Rating Scale in a geriatric residential population. J Am Geriatr Soc 1995; 43: 130–137.

    Article  CAS  Google Scholar 

  7. Cockcroft DW, Gault MH . Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16: 31–41.

    Article  CAS  Google Scholar 

  8. Hallek M, Fischer K, Fingerle-Rowson G, Fink AM, Busch R, Mayer J et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet 2010; 376: 1164–1174.

    Article  CAS  Google Scholar 

  9. Tam CS, O'Brien S, Wierda W, Kantarjian H, Wen S, Do KA et al. Long-term results of the fludarabine, cyclophosphamide, and rituximab regimen as initial therapy of chronic lymphocytic leukemia. Blood 2008; 112: 975–980.

    Article  CAS  Google Scholar 

  10. Hillmen P, Robak T, Janssens A, Govindbabu K, Grosicki S, Mayer J et al. Ofatumumab+chlorambucil versus chlorambucil alone in patients with untreated chronic lymphocytic leukemia (CLL): results of the phase III study complement 1 (OMB110911). Blood 2013; 122: 528.

    Google Scholar 

  11. Burger JA, Keating MJ, Wierda WG, Hartmann E, Hoellenriegel J, Rosin NY et al. Safety and activity of ibrutinib plus rituximab for patients with high-risk chronic lymphocytic leukaemia: a single-arm, phase 2 study. Lancet Oncol 2014; 15: 1090–1099.

    Article  CAS  Google Scholar 

  12. Byrd JC, Brown JR, O'Brien S, Barrientos JC, Kay NE, Reddy NM et al. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med 2014; 371: 213–223.

    Article  Google Scholar 

  13. Furman RR, Sharman JP, Coutre SE, Cheson BD, Pagel JM, Hillmen P et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med 2014; 370: 997–1007.

    Article  CAS  Google Scholar 

  14. O'Brien S, Furman RR, Coutre SE, Sharman JP, Burger JA, Blum KA et al. Ibrutinib as initial therapy for elderly patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: an open-label, multicentre, phase 1b/2 trial. Lancet Oncol 2014; 15: 48–58.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department I of Internal Medicine, German CLL Study Group (GCLLSG), Center of Integrated Oncology Cologne-Bonn, University of Cologne, Cologne, Germany

    V Goede, K Fischer, A Engelke & M Hallek

  2. Oncology Practice, Würzburg, Germany

    R Schlag

  3. Department of Hematology, Centre Henri Becquerel, Rouen, France

    S Lepretre

  4. Department of Hematology, Hospital Virgen de la Salud, Toledo, Spain

    L F C Montero

  5. Department of Hematology and Oncology, Ospedale Niguarda Ca’ Granda, Milan, Italy

    M Montillo

  6. Department of Hematology, University Hospital of Wales, Cardiff, UK

    C Fegan

  7. F. Hoffmann-La Roche Ltd, Basel, Switzerland

    E Asikanius & G Fingerle-Rowson

  8. F. Hoffmann-La Roche Ltd, Welwyn, UK

    K Humphrey

  9. Cluster of Excellence ‘Cellular Stress Responses in Aging Associated Diseases’ (CECAD), University of Cologne, Cologne, Germany

    M Hallek

Authors
  1. V Goede
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K Fischer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A Engelke
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R Schlag
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S Lepretre
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. L F C Montero
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M Montillo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. C Fegan
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. E Asikanius
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. K Humphrey
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. G Fingerle-Rowson
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. M Hallek
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to V Goede.

Ethics declarations

Competing interests

VG, MM, CF and MH received honoraria from Roche. VG, KF and MH received research funding from Roche. AE received travel grants from Roche. VG, SL, MM, CF and MH declared consultancy or board membership for Roche. EA, KH and GF are paid employees and stockholders of Roche. The other authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Goede, V., Fischer, K., Engelke, A. et al. Obinutuzumab as frontline treatment of chronic lymphocytic leukemia: updated results of the CLL11 study. Leukemia 29, 1602–1604 (2015). https://doi.org/10.1038/leu.2015.14

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2015.14

This article is cited by

Search

Advanced search

Quick links