Guidelines for alemtuzumab treatment in chronic lymphocytic leukaemia (CLL)

Česká verzia

Authors: Pracovní Skupina České Cll Skupiny (čscll) České Hematologické Společnosti České Lékařské Společnosti J. E. Purkyně L. Smolej ¹; V. Procházka ² ; M. Špaček ³; P. Obrtlíková ⁴; J. Gumulec ⁵; S. Vokurka ⁶; M. Doubek ⁷
Authors place of work: Oddělení klinické hematologie II. interní kliniky Lékařské fakulty UK a FN Hradec Králové, přednosta prof. MUDr. Jaroslav Malý, CSc. ¹; Hemato-onkologická klinika Lékařské fakulty UP a FN Olomouc, přednosta prof. MUDr. Karel Indrák, DrSc. ²; Oddělení klinické hematologie FN Královské Vinohrady Praha, přednosta doc. MUDr. Tomáš Kozák, Ph. D., MBA. ³; I. interní klinika 1. lékařské fakulty UK a VFN Praha, přednosta prof. MUDr. Marek Trněný, CSc. ⁴; Ústav klinické hematologie FN Ostrava, přednosta prim. MUDr. Jaromír Gumulec ⁵; Hematologicko-onkologické oddělení FN Plzeň, přednosta prim. MUDr. Vladimír Koza ⁶; Interní hematologická a onkologická klinika Lékařské fakulty MU a FN Brno, pracoviště Bohunice, přednosta prof. MUDr. Jiří Mayer, CSc. ⁷
Published in the journal: Vnitř Lék 2012; 58(3): 232-236
Category: Guidelines

Summary

Alemtuzumab, the humanized monoclonal anti-CD52 antibody, is an effective agent in the treatment of fludarabine-refractory chronic lymphocytic leukemia (CLL). Due to many specific issues associated with alemtuzumab treatment, the Working Committee of Czech CLL Study Group developed these guidelines. Summary of recommendations: (1) The main indication of alemtuzumab is fludarabine-refractory CLL. (2) Further possible indications include first-line treatment (in patients who cannot be treated by fludarabine-containing regimens), therapy of patients with del 17p, treatment of refractory autoimmune cytopenias and management of patients with severe cytopenias due to bone marrow infiltration. (3) The treatment should last 12 weeks and should not be terminated prematurely if there are no signs of CLL progression; bone marrow aspirate/biopsy can be performed after 12 weeks of treatment. (4) Subcutaneous administration of alemtuzumab seems to be equally effective with advantageous reduction of infusion-related adverse events. (5) Patients treated with alemtuzumab must receive combined antimicrobial prophylaxis against Pneumocystis jiroveci and herpetic viruses. Cytomegalovirus viremia should be monitored using weekly PCR from peripheral blood. (6) Use of alemtuzumab in combinations and consolidation/maintenance protocols must be considered experimental and needs optimization within prospective clinical trials. (7) Alemtuzumab treatment should be conducted by an experienced hematologist within a center of intensive hematology care.

Key words:
chronic lymphocytic leukemia – alemtuzumab – p53 – fludarabin – refractory CLL – recommendations

Zdroje

1. Panovská A, Doubek M, Brychtová Y et al. Chronic lymphocytic leukemia and focusing on epidemiology and management in everyday hematologic practice: recent data from the Czech Leukemia Study Group for Life (CELL). Clin Lymphoma Myeloma Leuk 2010; 10: 297–300.

2. Stilgenbauer S, Zenz T. Understanding and managing ultra high-risk chronic lymphocytic leukemia. Hematology Am Soc Hematol Educ Program 2010; 2010: 481–488.

3. Válková V, Cetkovský P. Současná role transplantace hematopoetických kmenových buněk v léčbě chronické lymfocytární leukemie. Transf Hematol dnes 2010; 16 (Suppl 1): 81–87.

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

5. Alinari L, Lapalombella R, Andritsos L et al. Alemtuzumab (Campath-1H) in the treatment of chronic lymphocytic leukemia. Oncogene 2007; 26: 3644–3653.

6. Badoux XC, Keating MJ, Wierda WG. What is the best frontline therapy for patients with CLL and 17p deletion? Curr Hematol Malig Rep 2011; 6: 36–46.

7. Rai KR. Novel therapeutic strategies with alemtuzumab for chronic lymphocytic leukemia. Semin Oncol 2006; 33 (2 Suppl 5): S15–S22.

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

9. Osterborg A, Foa R, Bezares RF et al. Management guidelines for the use of alemtuzumab in chronic lymphocytic leukemia. Leukemia 2009; 23: 1980–1988.

10. Berková A, Michalová K. Cytogenetické nálezy u chronické lymfocytární leukemie (CLL). Trans Hemat dnes 2010; 16 (Suppl 1): 52–55.

11. Papajík T, Urbanová R, Procházka V. Monoklonální protilátky v léčbě chronické lymfocytární leukemie. Trans Hemat dnes 2010; 16 (Suppl 1): 74–80.

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

13. Hallek M, Fischer K, Fingerle-Rowson G et al. International Group of Investigators; German Chronic Lymphocytic Leukaemia Study Group. 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.

14. Dearden C. Disease-specific complications of chronic lymphocytic leukemia. Hematology Am Soc Hematol Educ Program 2008: 450–456.

15. Osterborg A, Karlsson C, Lundin J. Alemtuzumab to treat refractory autoimmune hemolytic anemia or thrombocytopenia in chronic lymphocytic leukemia. Curr Hematol Malig Rep 2009; 4: 47–53.

16. MabCampath Summary of Product Characteristics. http://www.ema.europa.eu/ docs/en_GB/document_library/EPAR_-_Product_Information/human/000353/ WC500025270.pdf. Navštíveno 20.10.2011.

17. Dearden CE, Matutes E. Alemtuzumab in T-cell lymphoproliferative disorders. Best Pract Res Clin Haematol 2006; 19: 795–810.

18. Enblad G, Hagberg H, Erlanson M et al. A pilot study of alemtuzumab (anti-CD52 monoclonal antibody) therapy for patients with relapsed or chemotherapy-refractory peripheral T-cell lymphomas. Blood 2004; 103: 2920–2924.

19. Elter T, Borchmann P, Schulz H et al. Fludarabine in combination with alemtuzumab is effective and feasible in patients with relapsed or refractory B-cell chronic lymphocytic leukemia: results of a phase II trial. J Clin Oncol 2005; 23: 7024–7031.

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

21. Letestu R, Lepretre S, Arnoulet Ch et al. CLL2007FMP, a Phase III Randomized Multicentric Trial of the French Cooperative Group On CLL and WM (FCGCLL/MW) and the “Groupe Ouest-Est D’etudes Des Leucémies Aigües Et Autres Maladies Du Sang” (GOELAMS) : Immunochemotherapy with Fludarabine (F), Cyclophosphamide (C), and Rituximab (R) (FCR) Yields a Significantly Better Response Than Fludarabine (F), Cyclophosphamide (C) and MabCampath (Cam) (FCCam) In Previously Untreated B-Chronic Lymphocytic Leukemia Patients as Evaluated by a Sensitive 6 Color Flow Cytometry MRD. Blood (Annual Meeting Abstracts) 2010; 116: abstract 698.

22. Badoux XC, Keating MJ, Wang X et al. Cyclophosphamide, fludarabine, alemtuzumab, and rituximab as salvage therapy for heavily pretreated patients with chronic lymphocytic leukemia. Blood 2011; 118: 2085–2093.

23. Parikh SA, Keating MJ, O’Brien S et al. Frontline chemoimmunotherapy with fludarabine, cyclophosphamide, alemtuzumab, and rituximab for high-risk chronic lymphocytic leukemia. Blood 2011; 118: 2062–2068.

24. Schweighofer CD, Ritgen M, Eichhorst BF et al. Consolidation with alemtuzumab improves progression-free survival in patients with chronic lymphocytic leukaemia (CLL) in first remission – long-term follow-up of a randomized phase III trial of the German CLL Study Group. Br J Haematol 2009; 144: 95–98.

25. Lin TS, Donohue KA, Lucas MS et al. Consolidation Therapy with Subcutaneous (SC) Alemtuzumab Results in Severe Infectious Toxicity in Previously Untreated CLL Patients Who Achieve a Complete Response (CR) after Fludarabine and Rituximab (FR) Induction Therapy: Interim Safety Analysis of the CALGB Study 10101. Blood (Annual Meeting Abstracts) 2007; 110: abstract 755.

26. Fiegl M, Falkner F, Steurer M et al. Austrian Collaborative Study Group on Alemtuzumab in Chronic Lymphocytic Leukemia; Czech Leukemia Study Group for Life; CELL. Successful alemtuzumab retreatment in progressive B-cell chronic lymphocytic leukemia: a multicenter survey in 30 patients. Ann Hematol 2011; 90: 1083–1091.

27. Lundin J, Kimby E, Björkholm M et al. Phase II trial of subcutaneous anti-CD52 monoclonal antibody alemtuzumab (Campath-1H) as first-line treatment for patients with B-cell chronic lymphocytic leukemia (B-CLL). Blood 2002; 100: 768–773.

28. Stilgenbauer S, Zenz T, Winkler D et al. German Chronic Lymphocytic Leukemia Study Group. 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 2009; 27: 3994–4001.

29. Karlsson C, Lundin J, Kimby E et al. Phase II study of subcutaneous alemtuzumab without dose escalation in patients with advanced-stage, relapsed chronic lymphocytic leukaemia. Br J Haematol 2009; 144: 78–85.

30. Keating M, Coutré S, Rai K et al. Management guidelines for use of alemtuzumab in B-cell chronic lymphocytic leukemia. Clin Lymphoma 2004; 4: 220–227.

31. Bokemeyer C, Aapro MS, Courdi A et al. European Organisation for Research and Treatment of Cancer (EORTC) Taskforce for the Elderly. EORTC guidelines for the use of erythropoietic proteins in anaemic patients with cancer: 2006 update. Eur J Cancer 2007; 43: 258–270.

32. Thursky KA, Worth LJ, Seymour JF et al. Spectrum of infection, risk and recommendations for prophylaxis and screening among patients with lymphoproliferative disorders treated with alemtuzumab. Br J Haematol 2006; 132: 3–12.

33. O’Brien SM, Keating MJ, Mocarski ES. Updated guidelines on the management of cytomegalovirus reactivation in patients with chronic lymphocytic leukemia treated with alemtuzumab. Clin Lymphoma Myeloma 2006; 7: 125–130.