OBINUTUZUMAB FOR THE TREATMENT OF CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS: SINGLE CENTER EXPERIENCE
TREATMENT OF CHRONIC LYMPHOCYTIC LEUKEMIA
Keywords:
chronic lymphocytic leukemia, anti-CD20 monoclonal antibody, obinutuzumab, treatmentAbstract
Monoclonal antibodies (mAbs) targeting CD20 molecule on B lymphocyte are of great importance in the treatment of B-cell malignancies. In recent years a great effort has been put in developing novel mAbs that can provide greater efficacy than the well-known rituximab. A second class of mAbs obinutuzumab has been presented as a more powerful tool in the treatment of this group of patients. In this retrospective study 70 patients with symptomatic CLL were included. CLL patients were diagnosed and treated at the University Clinic for Hematology between January 2018 and January 2022. All patients were evaluated for traditional clinical and laboratory prognostic factors and newer prognostic factors including IGHV mutation status and CLL prognostic and predictive genetic abnormalities. Most of the patients treated with obinutuzumab had Binet B stage (56%). Mutational status of the immunoglobulin variable region heavy chain (IGHV) in most of CLL patients treated with obinutuzumab was unmated IGHV gene. The most frequently encountered adverse events were tumor lysis syndrome and leukopenia. The analysis of the initial results of the application of obinutuzumab-based therapy allows us to conclude that this therapeutical modality is not associated with severe adverse events that would limit the administration of therapy.
References
Glennie M, French R, Cragg M, Taylor R. Mechanisms of killing by anti-CD20 monoclonal antibodies. Mol Immunol 2007; 44: 3823-3837. doi: 10.1016/j.molimm. 2007.06.151.
Hallek M, Fischer K, Fingerle-Rowson G, Fink A, 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. doi: 10.1016/S0140-6736(10)61381-5.
Hainsworth J, Litchy S, Barton J, Houston G, Hermann R, Bradof J, et al. Single-agent rituximab as first-line and maintenance treatment for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma: a phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol 2003; 21: 1746-1751. doi: 10.1200/JCO.2003.09.027.
Dalle S, Reslan L, Besseyre de Horts T, Herveau S, Herting F, Plesa A, et al. Preclinical studies on the mechanism of action and the anti-lymphoma activity of the novel anti-CD20 antibody GA101. Mol Cancer Ther 2011; 10: 178-185. doi: 10.1158/1535-7163. MCT-10-0385.
Niederfellner G, Lammens A, Mundigl O, Georges G, Schaefer W, Schwaiger M, et al. Epitope characterization and crystal structure of GA101 provide insights into the molecular basis for type I/II distinction of CD20 antibodies. Blood 2011; 118: 358-367. doi: 10.1182/blood-2010-09-305847.
Golay J, Da Roit F, Bologna L, Ferrara C, Leusen J, Rambaldi A, et al. Glycoengineered CD20 antibody obinutuzumab activates neutrophils and mediates phagocytosis through CD16B more efficiently than rituximab. Blood 2013; 122: 3482-3491. doi: 10.1182/blood- 2013-05-504043.
Alduaij W, Ivanov A, Honeychurch J, Cheadle E, Potluri S, Lim S, et al. Novel type II anti-CD20 monoclonal antibody (GA101) evokes homotypic adhesion and actin-dependent, lysosome-mediated cell death in B-cell malignancies. Blood 2011; 117: 4519-4529. doi: 10.1182/blood-2010-07-296913.
Reslan L, Dalle S, Herveau S, Perrial E, Dumontet C. Apoptotic induction by anti-CD20 antibodies in chronic lymphocytic leukemia: comparison of rituximab and obinutuzumab. Leuk Lymphoma 2014; 55: 188-190. doi: 10.3109/10428194. 2013.788175.
Pedersen A, Jungersen M, Pedersen C. Monocytes mediate shaving of B-cell-bound anti-CD20 antibodies. Immunology 2011; 133: 239-245. doi: 10.1111/j.1365-2567.2011. 03434.x.
Klepfish A, Gilles L, Ioannis K, Rachmilewitz E, Schattner A. Enhancing the action of rituximab in chronic lymphocytic leukemia by adding fresh frozen plasma: complement/ rituximab interactions & clinical results in refractory CLL. Ann NY Acad Sci 2009; 1173: 865-873. doi: 10.1111/j.1749-6632.2009.04803.x.
Hiraga J, Tomita A, Sugimoto T, Shimada K, Ito M, Nakamura S, et al. Down-regulation of CD20 expression in B-cell lymphoma cells after treatment with rituximab-containing combination chemotherapies: its prevalence and clinical significance. Blood 2009; 113: 4885-4893. doi: 10.1182/blood-2008-08-175208.
Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Döhner H, et al. iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL. Blood 2018; 131(25): 2745-2760. doi: 10.1182/blood-2017-09-806398.
Brown J, O’Brien S, Kingsley C, Eradat H, Pagel J, Lymp J, et al. Safety and efficacy of obinutuzumab (GA101) with fludarabine/cyclophosphamide (G-FC) or bendamustine (G-B) in the initial therapy of patients with chronic lymphocytic leukemia (CLL): results from the phase 1b galton trial (GAO4779g). Blood 2013; 122: 523a. doi: 10.1182/blood-2014-12-613570.
Goede V, Fischer K, Busch R, Engelke A, Eichhorst B, Wendtner C, et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med 2014; 370: 1101-1110. doi: 10.1056/NEJMoa1313984. Epub 2014 Jan 8.
Cartron G, de Guibert S, Dilhuydy M, Morschhauser F, Leblond V, Dupuis J, et al. Obinutuzumab (GA101) in relapsed/refractory chronic lymphocytic leukemia: final data from the phase 1/2 GAUGUIN study. Blood 2014; 124: 2196-2202. doi: 10.1182/blood-2014-07-586610.
Shafat T, Grupel D, Porges T, Levi I, Yagel Y, Nesher L. Treatment with obinutuzumab leads to worse outcomes in haematological patients diagnosed with Omicron variant COVID-19. Br J Haematol 2022; 198(5): 826-829. doi: 10.1111/bjh.18315.