Skip to main content

Advertisement

SpringerLink
Log in

Alemtuzumab in chronic lymphocytic leukemia: final results of a large observational multicenter study in mostly pretreated patients

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

This retrospective study evaluated the benefit of alemtuzumab monotherapy in unselected patients with advanced B-cell chronic lymphocytic leukemia (CLL) and prolymphocytic leukemia (B-PLL) to definitely describe the impact of this antibody in clinical routine use. Data were collected from 208 consecutive, mainly pretreated, patients with CLL (n = 202), and B-PLL (n = 6) who had received alemtuzumab. Response, progression-free survival (PFS), and overall survival (OS) in various settings were assessed, and toxicities were documented. In these routine patients, a comparably low cumulative dose of alemtuzumab (median, 403 mg) was applied. In CLL, overall response rate was 32 %, and various pre-therapeutic parameters were predictive for inferior response, among them, the prior administration of ≥3 therapy lines (P < 0.001), refractoriness to fludarabine (P = 0.002), and bulky lymphadenopathy (P = 0.003). PFS and OS after start of alemtuzumab were 6.2 and 21.0 months, respectively. Bulky lymphadenopathy was the prominent risk factor for both inferior PFS (P < 0.001) and OS (P = 0.002). In B-PLL, four patients experienced a fatal outcome, whereas two patients had some benefit with alemtuzumab. The main adverse effects were CMV reactivation (20 %) and a broad spectrum of infections, which together were the main reasons for treatment interruption and/or premature termination. In conclusion, alemtuzumab administered even at low dose levels was effective but overall considerably toxic in routine CLL patients. We emphasize that alemtuzumab remains an important therapeutic option in subsets of CLL patients.

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

Similar content being viewed by others

References

  1. Keating MJ, Flinn I, Jain V et al (2002) Therapeutic role of alemtuzumab (Campath-1H) in patients who have failed fludarabine: results of a large international study. Blood 99:3554–3561

    Article  CAS  PubMed  Google Scholar 

  2. Rai KR, Freter CE, Mercier RJ et al (2002) Alemtuzumab in previously treated chronic lymphocytic leukemia patients who also had received fludarabine. J Clin Oncol 20:3891–3897

    Article  CAS  PubMed  Google Scholar 

  3. Fiegl M, Falkner A, Hopfinger G et al (2006) Austrian Collaborative Study Group on Alemtuzumab in Chronic Lymphocytic Leukemia. Routine clinical use of alemtuzumab in patients with heavily pretreated B-cell chronic lymphocytic leukemia: a nation-wide retrospective study in Austria. Cancer 107:2408–2416

    Article  CAS  PubMed  Google Scholar 

  4. Rieger K, Von Grünhagen U, Fietz T et al (2004) Efficacy and tolerability of alemtuzumab (CAMPATH-1H) in the salvage treatment of B-cell chronic lymphocytic leukemia—change of regimen needed? Leuk Lymphoma 45:345–349

    Article  CAS  PubMed  Google Scholar 

  5. Karlsson C, Norin S, Kimby E et al (2006) Alemtuzumab as first-line therapy for B-cell chronic lymphocytic leukemia: long-term follow-up of clinical effects, infectious complications and risk of Richter transformation. Leukemia 20:2204–2207

    Article  CAS  PubMed  Google Scholar 

  6. Osterborg A, Dyer MJ, Bunjes D et al (1997) Phase II multicenter study of human CD52 antibody in previously treated chronic lymphocytic leukemia. European Study Group of CAMPATH-1H Treatment in Chronic Lymphocytic Leukemia. J Clin Oncol 15:1567–1574

    CAS  PubMed  Google Scholar 

  7. Ferrajoli A, O’Brien SM, Cortes JE et al (2003) Phase II study of alemtuzumab in chronic lymphoproliferative disorders. Cancer 98:773–778

    Article  CAS  PubMed  Google Scholar 

  8. Moreton P, Kennedy B, Lucas G et al (2005) Eradication of minimal residual disease in B-cell chronic lymphocytic leukemia after alemtuzumab therapy is associated with prolonged survival. J Clin Oncol 23:2971–2979

    Article  CAS  PubMed  Google Scholar 

  9. Stilgenbauer S, Zenz T, Winkler D et al (2009) Subcutaneous alemtuzumab in fludarabine-refractory chronic lymphocytic leukemia: clinical results and prognostic marker analyses from the CLL2H study of the German Chronic Lymphocytic Leukemia Study Group. J Clin Oncol 27:3994–4001

    Article  CAS  PubMed  Google Scholar 

  10. Hillmen P, Skotnicki AB, Robak T et al (2007) Alemtuzumab compared with chlorambucil as first-line therapy for chronic lymphocytic leukemia. J Clin Oncol 25:5616–5623

    Article  CAS  PubMed  Google Scholar 

  11. Rai K, Keating MJ, Coutre S et al (2002) Patients with refractory B-CLL and T-PLL treated with alemtuzumab (Campath) on a compassionate basis. A report on efficacy and safety of CAM511 trial. Blood 100:(Abstr 3165)

  12. Lozanski G, Heerema NA, Flinn IW et al (2004) Alemtuzumab is an effective therapy for chronic lymphocytic leukemia with p53 mutations and deletions. Blood 103:3278–3281

    Article  CAS  PubMed  Google Scholar 

  13. Osuji NC, Del Giudice I, Matutes E et al (2005) The efficacy of alemtuzumab for refractory chronic lymphocytic leukemia in relation to cytogenetic abnormalities of p53. Haematologica 90:1435–1436

    CAS  PubMed  Google Scholar 

  14. Wickramanayake PD, Köppler H, Rohrberg R et al (2005) Use of alemtuzumab (MabCampath®) is safe and effective in an outpatient setting: interim analysis of a postmarketing surveillance. Onkologie 28(suppl3): 86 (Abstract 253)

    Google Scholar 

  15. Laros-van Gorkom BA, Huisman CA, Wijermans PW, Schipperus MR (2007) Experience with alemtuzumab in treatment of chronic lymphocytic leukaemia in the Netherlands. Neth J Med 65:333–338

    CAS  PubMed  Google Scholar 

  16. Hui D, Lam W, Toze C et al (2008) Alemtuzumab in clinical practice: a British Columbia experience. Leuk Lymphoma 49:218–226

    Article  CAS  PubMed  Google Scholar 

  17. Doubek M, Jungová A, Brejcha M, Panovská A, Brychtová Y, Pospísil Z, Mayer J (2009) Alemtuzumab in chronic lymphocytic leukemia treatment: retrospective analysis of outcome according to cytogenetics. Vnitr Lek 55:549–554

    CAS  PubMed  Google Scholar 

  18. Cortelezzi A, Gritti G, Laurenti L et al (2011) An Italian retrospective study on the routine clinical use of low-dose alemtuzumab in relapsed/refractory chronic lymphocytic leukaemia patients. Br J Haematol 156:481–489

    Article  PubMed  Google Scholar 

  19. Dearden CE, Matutes E, Cazin B et al (2001) High remission rate in T-cell prolymphocytic leukemia with CAMPATH-1H. Blood 98:1721–1726

    Article  CAS  PubMed  Google Scholar 

  20. Bowen AL, Zomas A, Emmett E, Matutes E, Dyer MJ, Catovsky D (1997) Subcutaneous CAMPATH-1H in fludarabine-resistant/relapsed chronic lymphocytic and B-prolymphocytic leukaemia. Br J Haematol 96:617–619

    Article  CAS  PubMed  Google Scholar 

  21. Chaar BT, Petruska PJ (2007) Complete response to alemtuzumab in a patient with B prolymphocytic leukemia. Am J Hematol 82:417

    Article  PubMed  Google Scholar 

  22. Dearden C (2012) How I treat prolymphocytic leukemia. Blood 120:538–551

    Article  CAS  PubMed  Google Scholar 

  23. Fiegl M, Erdel M, Tinhofer I et al (2010) Clinical outcome of pretreated B-cell chronic lymphocytic leukemia following alemtuzumab therapy: a retrospective study on various cytogenetic risk categories. Ann Oncol 21:2410–2419

    Article  CAS  PubMed  Google Scholar 

  24. Fiegl M, Falkner F, Steurer M et al (2011) Successful alemtuzumab retreatment in progressive B-cell chronic lymphocytic leukemia: a multicenter survey in 30 patients. Ann Hematol 90:1083–1091

    Article  CAS  PubMed  Google Scholar 

  25. Osterborg A, Foà R, Bezares RF et al (2009) Management guidelines for the use of alemtuzumab in chronic lymphocytic leukemia. Leukemia 23:1980–1988

    Article  CAS  PubMed  Google Scholar 

  26. Cheson BD, Bennett JM, Grever M et al (1996) National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood 87:4990–4997

    CAS  PubMed  Google Scholar 

  27. Fan L, Wang L, Zhang R et al (2012) Richter transformation in 16 of 149 Chinese patients with chronic lymphocytic leukemia. Leuk Lymphoma 53:1749–1756

    Article  CAS  PubMed  Google Scholar 

  28. Rossi D, Cerri M, Capello D et al (2008) Biological and clinical risk factors of chronic lymphocytic leukaemia transformation to Richter syndrome. Br J Haematol 142:202–215

    Article  CAS  PubMed  Google Scholar 

  29. Tsimberidou AM, O’Brien S, Khouri I et al (2006) Clinical outcomes and prognostic factors in patients with Richter’s syndrome treated with chemotherapy or chemoimmunotherapy with or without stem-cell transplantation. J Clin Oncol 24:2343–2351

    Article  CAS  PubMed  Google Scholar 

  30. Cortelezzi A, Pasquini MC, Gardellini A et al (2009) Low-dose subcutaneous alemtuzumab in refractory chronic lymphocytic leukaemia (CLL): results of a prospective, single-arm multicentre study. Leukemia 23:2027–2033

    Article  CAS  PubMed  Google Scholar 

  31. Bezares RF, Stemelin G, Diaz A et al (2011) Multicenter study of subcutaneous alemtuzumab administered at reduced dose in patients with fludarabine-relapsed/refractory chronic lymphocytic leukemia: final analysis. Leuk Lymphoma 52:1936–1941

    Article  CAS  PubMed  Google Scholar 

  32. Montillo M, Tedeschi A, Petrizzi VB et al (2011) An open-label, pilot study of fludarabine, cyclophosphamide, and alemtuzumab in relapsed/refractory patients with B-cell chronic lymphocytic leukemia. Blood 118:4079–4085

    Article  CAS  PubMed  Google Scholar 

  33. Gritti G, Reda G, Maura F et al (2012) Low dose alemtuzumab in patients with fludarabine-refractory chronic lymphocytic leukemia. Leuk Lymphoma 53:424–429

    Article  CAS  PubMed  Google Scholar 

  34. Hisada M, Biggar RJ, Greene MH et al (2001) Solid tumors after chronic lymphocytic leukemia. Blood 98:1979–1981

    Article  CAS  PubMed  Google Scholar 

  35. Dalia S, Chavez JC, Domingo G et al (2012) Incidence of second and secondary malignancies in patients with CLL: a single institution experience. J Clin Oncol 30(suppl; abstr 6568)

  36. Puttarajappa C, Yabes J, Bei L et al (2013) Cancer risk with alemtuzumab following kidney transplantation. Clin Transplant 27:E264–E271

    Article  CAS  PubMed  Google Scholar 

  37. Hercher C, Robain M, Davi F et al (2001) A multicentric study of 41 cases of B-prolymphocytic leukemia: two evolutive forms. Leuk Lymphoma 42:981–987

    Article  CAS  PubMed  Google Scholar 

  38. Shvidel L, Shtalrid M, Bassous L, Klepfish A, Vorst E, Berrebi A (1999) B-cell prolymphocytic leukemia: a survey of 35 patients emphasizing heterogeneity, prognostic factors and evidence for a group with an indolent course. Leuk Lymphoma 33:169–179

    CAS  PubMed  Google Scholar 

  39. Arnason JE, Brown JR (2011) Alemtuzumab use in relapsed and refractory chronic lymphocytic leukemia. Hematology Am Soc Hematol Educ Program 2011:119–120

    Article  PubMed  Google Scholar 

  40. Pettitt AR, Jackson R, Carruthers S et al (2012) Alemtuzumab in combination with methylprednisolone is a highly effective induction regimen for patients with chronic lymphocytic leukemia and deletion of TP53: final results of the national cancer research institute CLL206 trial. J Clin Oncol 30:1647–1655

    Article  CAS  PubMed  Google Scholar 

  41. Döhner H, Stilgenbauer S, Benner A et al (2000) Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med 343:1910–1916

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

Further contributors to this work included the following (Austrian centers unless indicated): W. Willenbacher, E Gunsilius (Innsbruck); G Webersinke (Linz); Martin Erdel (Linz); D Demirtas, M Shehata, U Jäger, N Zojer, G Tatzreiter, C Ganster (Vienna); B Walla (Dornbirn); S Hojas (Fürstenfeld); G Lobmaier (Ried); W Kanatschnig (Klagenfurt); J Thaler (Wels); F Bauer, M Speicher (Graz); S Cortelazzo, C Toldo, M Svaldi (Bozen/Italy); M Mitterer (Meran/Italy); and M Notdurfter (Bruneck/Italy). The authors wish to thank Mr. Jeffrey McCabe for editorial support. Bayer Schering Pharma Vienna GmbH provided funding (travel costs, 2007).

Note added

In August 2012, Genzyme surrendered the approved license of alemtuzumab, pending regulatory approval to reintroduce it as a treatment for multiple sclerosis. The authors of this article, convinced that alemtuzumab has an important role in the therapy of subsets of CLL patients [39, 40], regret this step and raise ethical concerns on this decision.

Conflict of interest

The authors declare that they have no conflict of interest.

Statement of informed consent

Due to the retrospective nature of this study, informed consent was not needed.

Author information

Authors and Affiliations

  1. Department of Internal Medicine V (Hematology and Oncology), Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria

    M. Fiegl, R. Stauder, M. Steurer, M. Mian & G. Gastl

  2. Department of Internal Medicine III, Hanuschspital, Vienna, Austria

    G. Hopfinger

  3. Department of Internal Medicine, Hematology and Oncology, University Hospital of Brno and CEITEC, Masaryk University, Brno, Czech Republic

    Y. Brychtova & J. Mayer

  4. Department of Internal Medicine I, Hematology, Medical University of Vienna, Vienna, Austria

    C. Skrabs

  5. Department of Internal Medicine, Hospital of Kufstein, Kufstein, Austria

    A. Zabernigg

  6. Department of Internal Medicine, Hospital of Bregenz, Bregenz, Austria

    F. Schmid

  7. Department of Internal Medicine, Hospital of Vöcklabruck, Vöcklabruck, Austria

    F. Haslbaur

  8. Department of Internal Medicine, City Hospital of Dornbirn, Dornbirn, Austria

    G. Winder

  9. Department of Internal Medicine, Hospital of Lienz, Lienz, Austria

    A. Walder

  10. Department of Internal Medicine, Academic Hospital of Feldkirch, Feldkirch, Austria

    A. Lang

  11. First Department of Internal Medicine, General Hospital of Linz, Linz, Austria

    D. Voskova

  12. Department of Internal Medicine III, Private Medical University of Salzburg, Salzburg, Austria

    R. Greil

Authors
  1. M. Fiegl
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. Stauder
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Steurer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Mian
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G. Hopfinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Y. Brychtova
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. C. Skrabs
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. A. Zabernigg
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. F. Schmid
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. F. Haslbaur
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. G. Winder
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. A. Walder
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. A. Lang
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. D. Voskova
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. R. Greil
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. J. Mayer
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. G. Gastl
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

for The Austrian Collaborative Study Group on Alemtuzumab in Chronic Lymphocytic Leukemia, in cooperation with The Czech Leukemia Study Group for Life, CELL

Corresponding author

Correspondence to M. Fiegl.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fiegl, M., Stauder, R., Steurer, M. et al. Alemtuzumab in chronic lymphocytic leukemia: final results of a large observational multicenter study in mostly pretreated patients. Ann Hematol 93, 267–277 (2014). https://doi.org/10.1007/s00277-013-1966-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-013-1966-z

Keywords

Search

Navigation