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Chemoimmunotherapy with GA101 plus chlorambucil in patients with chronic lymphocytic leukemia and comorbidity: results of the CLL11 (BO21004) safety run-in

Leukemia volume 27, pages 1172–1174 (2013)Cite this article

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Intensive chemoimmunotherapy with fludarabine, cyclophosphamide and rituximab is the standard first line treatment in younger and physically fit patients with chronic lymphocytic leukemia (CLL).1 Older and physically less fit patients with CLL have been underrepresented in past clinical trials and, therefore, no standard of care has been established for these so far. Treating such patients with the alkylating drug chlorambucil (CLB) remains a valuable option,2, 3 but complete remissions are generally rare and disease progression mostly occurs <2 years after the start of therapy. The addition of CD20-antibodies to CLB has been proposed to improve alkylator-based therapy of CLL. Two recent phase 2 trials explored chemoimmunotherapy with CLB and rituximab and reported higher complete response rates compared with those historically observed with CLB monotherapy.4, 5 Outcome of treatments combining CLB with novel CD20-antibodies (for example, obinutuzumab, ofatumumab, veltuzumab) has not yet been published. It, therefore, has remained unclear whether such regimens are safe and feasible in patients with CLL, particularly if those patients are of advanced age and afflicted with comorbidity.

Obinutuzumab (GA101) is a glycoengineered, humanized type II CD20-antibody that has demonstrated superior activity compared with type I antibodies in preclinical studies.6, 7, 8 In phase 1/2 trials, monotherapy with GA101 in patients with relapsed or refractory CLL has been shown to be safe and with promising activity.9, 10 Therefore, a multicenter international 3-arm protocol (CLL11/BO21004) was initiated comparing GA101 plus CLB (G-CLB) with rituximab plus CLB (R-CLB) or CLB alone in previously untreated CLL patients with increased comorbidity. Before the opening of randomization, six subjects with CLL received G-CLB treatment within a safety run-in phase to investigate whether this treatment combination is feasible in a patient population characterized by an increased burden of comorbidity.

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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. Department of Geriatric Medicine and Research, St Marien Hospital and University of Cologne, Cologne, Germany

    V Goede

  3. Institute of Medical Statistics and Epidemiology (IMSE), Technical University of Munich, Munich, Germany

    R Busch

  4. Department of Internal Medicine I, Division of Hematology and Hemostaseology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria

    U Jaeger

  5. Service d’Hématologie Clinique et Thérapie Cellulaire, Pôle de Médicine, CHU de Bordeaux, Bordeaux, France

    M-S Dilhuydy

  6. Adelaide Cancer Center, University of Adelaide, Adelaide, South Australia, Australia

    N Wickham

  7. Service d’Hématologie, Pôles de Médicines Specialisées, CHU Rennes, Rennes, France

    S De Guibert

  8. Department of Medicine II, University of Schleswig-Holstein, Kiel, Germany

    M Ritgen

  9. Department of Immunology, Erasmus Medical Center, Rotterdam, The Netherlands

    A W Langerak

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

    G Bieska, K Humphrey & M Wenger

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

    M Hallek

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  1. V Goede
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Correspondence to V Goede.

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Competing interests

VG, KF and MH received honoraria and travel grants from Roche. MH declared consultancy and board membership for Roche. GB, KH and MW are paid employees of Roche. The remaining authors declare no conflict of interest.

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Goede, V., Fischer, K., Busch, R. et al. Chemoimmunotherapy with GA101 plus chlorambucil in patients with chronic lymphocytic leukemia and comorbidity: results of the CLL11 (BO21004) safety run-in. Leukemia 27, 1172–1174 (2013). https://doi.org/10.1038/leu.2012.252

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