Online first

Assessment of the efficacy of ofatumumab in patients with chronic lymphocytic leukaemia treated in the Department of Haematooncology and Bone Marrow Transplantation of the Medical University in Lublin – Prelimary results

Agnieszka Szymczyk 1, 2  ,  
Adam Nogalski 3,  
Department of Haematooncology and Bone Marrow Transplantation, Medical University
Independent Transplantology Unit, Medical University of Lublin, Lublin
Department of Trauma Surgery and Emergency Medicine, Medical University of Lublin, Poland
Despite significant recent advances in the treatment of chronic lymphocytic leukaemia (CLL), most cases of the disease are still incurable. Treatment with monoclonal antibodies, such as ofatumumab, is one of the new therapeutic options.

Retrospective analysis of the efficacy of ofatumumab in patients with chronic lymphocytic leukaemia (CLL) treated in the Haematooncology and Bone Marrow Transplantation Department of the Medical University of Lublin, Poland, during 2011–2013.

Material and Methods:
The analysis included 5 patients (3 women and 2 men), aged 47–65, with Rai stage II-IV CLL, after a few lines of treatment. Three patients received ofatumumab in monotherapy and 2 patients received ofatumumab in combination with cyclophosphamide (50 mg/day) and dexamethasone (40 mg/day). All patients included in the study were diagnosed with an active form of leukaemia with symptoms such as lymphocytosis or massive lymphadenopathy.

All patients responded to the treatment. Within the first 8 weeks of the treatment, levels of white blood cells returned to normal in patients with baseline lymphocytosis (3 patients). An increase in platelet levels was reported in 3 patients. Haemoglobin levels were higher or comparable to the baseline values in all studied patients after the completion of immunotherapy. In the patient with massive lymphadenopathy and hepato- and splenomegaly, the size of the lymph nodes, spleen and liver decreased and neutrophil levels increased. Time of progression was 5–12 months, and in one patient partial remission has been maintained. The treatment was well-tolerated in most cases. Asymptomatic neutropenia and an infection with Candida glabrata were observed.

Ofatumumab may be a new and safe therapeutic option for patients with CLL after a few lines of treatment.

Agnieszka Szymczyk   
Department of Haematooncology and Bone Marrow Transplantation, Medical University
1. Gupta IV, Jewell RC. Ofatumumab, the first human anti-CD20 monoclonal antibody for the treatment of B cell hematologic malignancies. Ann N Y Acad Sci. 2012; 1263: 43–56.
2. Dyer MJ. Safety and efficacy of ofatumumab in patients with fludarabine and alemtuzumab refractory chronic lymphocytic leukaemia. Ther Adv Hematol. 2012; 3(4): 199–207.
3. Dudziński M. Miejsce ofatumumabu w terapii chłoniaków B-komórkowych. Hematologia 2011; 2(3): 246–255.
4. Keating MJ, O’Brien S, Kontoyiannis D, Plunkett W, Koller C, Beran M, Lerner S, Kantarjian H. Results of first salvage therapy for patients refractory to a fludarabine regimen in chronic lymphocytic leukemia. Leuk Lymphoma. 2002; 43(9): 1755–1762.
5. Tam CS, O’Brien S, Lerner S, Khouri I, Ferrajoli A, Faderl S, Browning M, Tsimberidou AM, Kantarjian H, Wierda WG. The natural history of fludarabine-refractory chronic lymphocytic leukemia patients who fail alemtuzumab or have bulky lymphadenopathy. Leuk Lymphoma. 2007; 48(10): 1931–1939.
6. Teeling JL, French RR, Cragg MS, van den Brakel J, Pluyter M, Huang H, Chan C, Parren PW, Hack CE, Dechant M, Valerius T, van de Winkel JG, Glennie MJ. Characterization of new human CD20 monoclonal antibodies with potent cytolytic activity against non-Hodgkin lymphomas. Blood. 2004; 104(6): 1793–1800.
7. Teeling JL, Mackus WJ, Wiegman LJ, van den Brakel JH, Beers SA, French RR, van Meerten T, Ebeling S, Vink T, Slootstra JW, Parren PW, Glennie MJ, van de Winkel JG. The biological activity of human CD20 monoclonal antibodies is linked to unique epitopes on CD20. J Immunol. 2006; 177(1): 362–371.
8. Coiffier B, Lepretre S, Pedersen LM, Gadeberg O, Fredriksen H, van Oers MH, Wooldridge J, Kloczko J, Holowiecki J, Hellmann A, Walewski J, Flensburg M, Petersen J, Robak T. Safety and efficacy of ofatumumab, a fully human monoclonal anti-CD20 antibody, in patients with relapsed or refractory B-cell chronic lymphocytic leukemia: a phase 1–2 study. Blood. 2008; 111(3): 1094–1100.
9. Wierda WG, Kipps TJ, Mayer J, Stilgenbauer S, Williams CD, Hellmann A, Robak T, Furman RR, Hillmen P, Trneny M, Dyer MJ, Padmanabhan S, Piotrowska M, Kozak T, Chan G, Davis R, Losic N, Wilms J, Russell CA, Osterborg A. Ofatumumab as single-agent CD20 immunotherapy in fludarabine-refractory chronic lymphocytic leukemia. J Clin Oncol. 2010; 28(10): 1749–1755.
10. Moreno C, Montillo M, Panayiotidis P, Dimou M, Bloor A, Dupuis J, Schuh A, Norin S, Geisler C, Hillmen P, Doubek M, Trněný M, Obrtlikova P, Laurenti L, Stilgenbauer S, Smolej L, Ghia P, Cymbalista F, Jaeger U, Stamatopoulos K, Stavroyianni N, Carrington P, Zouabi H, Leblond V, Gomez-Garcia JC, Rubio M, Marasca R, Musuraca G, Rigacci L, Farina L, Paolini R, Pospisilova S, Kimby E, Bradley C, Montserrat E. Ofatumumab in poor-prognosis chronic lymphocytic leukemia: a phase IV, non-interventional, observational study from the European Research Initiative on Chronic Lymphocytic Leukemia. Haematologica. 2015; 100(4): 511–516.
11. Castro JE, Choi MY, Carvajal T, Almahasnah E, Chang J, James DF, Kipps TJ. Ofatumumab and high-dose methylprednisolone for the treatment of patients with relapsed or refractory chronic lymphocytic leukemia. Blood Cancer J. 2014; 4: e258.
12. Doubek M, Brychtova Y, Panovska A, Sebejova L, Stehlikova O, Chovancova J, Malcikova J, Smardova J, Plevova K, Volfova P, Trbusek M, Mraz M, Bakesova D, Trizuljak J, Hadrabova M, Obrtlikova P, Karban J, Smolej L, Oltova A, Jelinkova E, Pospisilova S, Mayer J. Ofatumumab added to dexamethasone in patients with relapsed or refractory chronic lymphocytic leukemia: Results from a phase II study. Am J Hematol. 2015; 90(5): 417–421.
13. Cortelezzi A, Sciumè M, Liberati AM, Vincenti D, Cuneo A, Reda G, Laurenti L, Zaja F, Marasca R, Chiarenza A, Gritti G, Orsucci L, Storti S, Angelucci E, Cascavilla N, Gobbi M, Mauro FR, Morabito F, Fabris S, Piciocchi A, Vignetti M, Neri A, Rossi D, Giannarelli D, Guarini A, Foà R. Bendamustine in combination with ofatumumab in relapsed or refractory chronic lymphocytic leukemia: a GIMEMA Multicenter Phase II Trial. Leukemia. 2014; 28(3): 642–648.
14. Costa LJ, Fanning SR, Stephenson J Jr, Afrin LB, Kistner-Griffin E, Bentz TA, Stuart RK. Sequential ofatumumab and lenalidomide for the treatment of relapsed and refractory chronic lymphocytic leukemia and small lymphocytic lymphoma. Leuk Lymphoma. 2015; 56(3): 645–649.
Copy url