What is the status of novel anti-CD20 antibodies for chronic lymphocytic leukemia and are they set to leave rituximab in the shadows?

References

• Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer. J Clin 2015;65(1):5-29
   Google Scholar
• Hallek M, Fischer K, Fingerle-Rowson G, 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(9747):1164-74
   PubMed Web of Science ®Google Scholar
• Köhler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 1975;256(5517):495-7
   PubMed Web of Science ®Google Scholar
• Stashenko P, Nadler LM, Hardy R, Schlossman SF. Characterization of a human B lymphocyte-specific antigen. J Immunol Baltim Md 1950;125(4):1678-85
   Google Scholar
• Tedder TF, Engel P. CD20: a regulator of cell-cycle progression of B lymphocytes. Immunol Today 1994;15(9):450-4
   PubMedGoogle Scholar
• Teeling JL, Mackus WJM, Wiegman LJJM, et al. The biological activity of human CD20 monoclonal antibodies is linked to unique epitopes on CD20. J Immunol Baltim Md 1950;177(1):362-71
   Google Scholar
• Cragg MS, Walshe CA, Ivanov AO, Glennie MJ. The biology of CD20 and its potential as a target for mAb therapy. Curr Dir Autoimmun 2005;8:140-74
   PubMedGoogle Scholar
• Li H, Ayer LM, Polyak MJ, et al. The CD20 calcium channel is localized to microvilli and constitutively associated with membrane rafts: antibody binding increases the affinity of the association through an epitope-dependent cross-linking-independent mechanism. J Biol Chem 2004;279(19):19893-901
   PubMed Web of Science ®Google Scholar
• McLaughlin P, Grillo-López AJ, Link BK, et al. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol 1998;16(8):2825-33
   PubMed Web of Science ®Google Scholar
• Huhn D, von Schilling C, Wilhelm M, et al. Rituximab therapy of patients with B-cell chronic lymphocytic leukemia. Blood 2001;98(5):1326-31
   PubMed Web of Science ®Google Scholar
• O’Brien SM, Kantarjian H, Thomas DA, et al.Rituximab dose-escalation trial in chronic lymphocytic leukemia. J Clin Oncol 2001;19(8):2165-70
   PubMed Web of Science ®Google Scholar
• Byrd JC, Murphy T, Howard RS, et al. Rituximab using a thrice weekly dosing schedule in B-cell chronic lymphocytic leukemia and small lymphocytic lymphoma demonstrates clinical activity and acceptable toxicity. J Clin Oncol 2001;19(8):2153-64
   PubMed Web of Science ®Google Scholar
• Robinson KS, Williams ME, van der Jagt RH, et al. Phase II multicenter study of bendamustine plus rituximab in patients with relapsed indolent B-cell and mantle cell non-Hodgkin’s lymphoma. J Clin Oncol 2008;26(27):4473-9
   PubMed Web of Science ®Google Scholar
• Fischer K, Cramer P, Busch R, et al. Bendamustine combined with rituximab in patients with relapsed and/or refractory chronic lymphocytic leukemia: a multicenter phase II trial of the German Chronic Lymphocytic Leukemia Study Group. J Clin Oncol 2011;29(26):3559-66
   PubMed Web of Science ®Google Scholar
• Fischer K, Cramer P, Busch R, et al. Bendamustine in combination with rituximab for previously untreated patients with chronic lymphocytic leukemia: a multicenter phase II trial of the German Chronic Lymphocytic Leukemia Study Group. J Clin Oncol 2012;30(26):3209-16
   PubMed Web of Science ®Google Scholar
• Byrd JC, Peterson BL, Morrison VA, et al. Randomized phase 2 study of fludarabine with concurrent versus sequential treatment with rituximab in symptomatic, untreated patients with B-cell chronic lymphocytic leukemia: results from Cancer and Leukemia Group B 9712 (CALGB 9712). Blood 2003;101(1):6-14
   PubMed Web of Science ®Google Scholar
• Faderl S, Thomas DA, O’Brien S, et al. Experience with alemtuzumab plus rituximab in patients with relapsed and refractory lymphoid malignancies. Blood 2003;101(9):3413-15
   PubMed Web of Science ®Google Scholar
• Frankfurt O, Ma S, Gordon L, et al. Phase II study of alemtuzumab-rituximab therapy in previously untreated patients with chronic lymphocytic leukemia: short- and long-term outcomes. Leuk Lymphoma 2015;56(2):315-23
   PubMed Web of Science ®Google Scholar
• Cragg MS, Morgan SM, Chan HTC, et al. Complement-mediated lysis by anti-CD20 mAb correlates with segregation into lipid rafts. Blood 2003;101(3):1045-52
   PubMed Web of Science ®Google Scholar
• Cheson BD. Ofatumumab, a novel anti-CD20 monoclonal antibody for the treatment of B-cell malignancies. J Clin Oncol 2010;28(21):3525-30
   PubMed Web of Science ®Google Scholar
• Coiffier B, Lepretre S, Pedersen LM, et al. 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):1094-100
   PubMed Web of Science ®Google Scholar
• Wierda WG, Kipps TJ, Mayer J, et al. Ofatumumab as single-agent CD20 immunotherapy in fludarabine-refractory chronic lymphocytic leukemia. J Clin Oncol 2010;28(10):1749-55
   PubMed Web of Science ®Google Scholar
• Cheson BD, Bennett JM, Grever M, et al. National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood 1996;87(12):4990-7
   PubMed Web of Science ®Google Scholar
• Wierda WG, Kipps TJ, Dürig J, et al. Chemoimmunotherapy with O-FC in previously untreated patients with chronic lymphocytic leukemia. Blood 2011;117(24):6450-8
   PubMed Web of Science ®Google Scholar
• Hillmen P, Robak T, Janssens A, et al. Chlorambucil plus ofatumumab versus chlorambucil alone in previously untreated patients with chronic lymphocytic leukaemia (COMPLEMENT 1): a randomised, multicentre, open-label phase 3 trial. Lancet 2015;385(9980):1873-83
   PubMed Web of Science ®Google Scholar
• Byrd JC, Furman RR, Coutre SE, et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med 2013;369(1):32-42
   PubMed Web of Science ®Google Scholar
• Byrd JC, Brown JR, O’Brien S, et al. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med 2014;371(3):213-23
   PubMed Web of Science ®Google Scholar
• Ujjani C, Ramzi P, Gehan E, et al. Ofatumumab and bendamustine in previously treated chronic lymphocytic leukemia and small lymphocytic lymphoma. Leuk Lymphoma 2015;56(4):915-20
   PubMed Web of Science ®Google Scholar
• Cortelezzi A, Sciumè M, Liberati AM, et al. Bendamustine in combination with ofatumumab in relapsed or refractory chronic lymphocytic leukemia: a GIMEMA Multicenter Phase II Trial. Leukemia 2014;28(3):642-8
   PubMed Web of Science ®Google Scholar
• Teeling JL, French RR, Cragg MS, et al. Characterization of new human CD20 monoclonal antibodies with potent cytolytic activity against non-Hodgkin lymphomas. Blood 2004;104(6):1793-800
   PubMed Web of Science ®Google Scholar
• Pawluczkowycz AW, Beurskens FJ, Beum PV, et al. Binding of submaximal C1q promotes complement-dependent cytotoxicity (CDC) of B cells opsonized with anti-CD20 mAbs ofatumumab (OFA) or rituximab (RTX): considerably higher levels of CDC are induced by OFA than by RTX. J Immunol Baltim Md 1950;183(1):749-58
   Google Scholar
• Wierda WG, Padmanabhan S, Chan GW, et al. Ofatumumab is active in patients with fludarabine-refractory CLL irrespective of prior rituximab: results from the phase 2 international study. Blood 2011;118(19):5126-9
   PubMed Web of Science ®Google Scholar
• Research C for DE and. Approved drugs - ofatumumab [Internet]. Available from: www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm393823.htm [Last accessed 11 June 2015]
   Google Scholar
• Press announcements - FDA approves new treatment for chronic lymphocytic leukemia [Internet]. Available from: www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm187966.htm [Last accessed 11 June 2015]
   Google Scholar
• Mössner E, Brünker P, Moser S, et al. Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cell-mediated B-cell cytotoxicity. Blood 2010;115(22):4393-402
   PubMed Web of Science ®Google Scholar
• Alduaij W, Ivanov A, Honeychurch J, 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(17):4519-29
   PubMed Web of Science ®Google Scholar
• Patz M, Isaeva P, Forcob N, et al. Comparison of the in vitro effects of the anti-CD20 antibodies rituximab and GA101 on chronic lymphocytic leukaemia cells. Br J Haematol 2011;152(3):295-306
   PubMed Web of Science ®Google Scholar
• Cartron G, de Guibert S, Dilhuydy MS, et al. Obinutuzumab (GA101) in relapsed/refractory chronic lymphocytic leukemia: final data from the phase 1/2 GAUGUIN study. Blood 2014;124(14):2196-202
   PubMed Web of Science ®Google Scholar
• Obinutuzumab (GA101) 1,000 mg versus 2,000 mg in patients with chronic lymphocytic leukemia (CLL): Results of the phase II GAGE (GAO4768g) trial. 2014 ASCO Annual Meeting Abstracts Meeting Library [Internet]. Available from: http://meetinglibrary.asco.org/content/132812-144 [Last Accessed 10 August 2015]
   Google Scholar
• Brown JR, O’Brien S, Kingsley CD, et al. Obinutuzumab plus fludarabine/cyclophosphamide or bendamustine in the initial therapy of CLL patients: the phase 1b GALTON trial. Blood 2015;125(18):2779-85
   PubMed Web of Science ®Google Scholar
• Press announcements-FDA approves Gazyva for chronic lymphocytic leukemia [Internet]. Available from: www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm373209.htm [Last accessed 11 June 2015]
   Google Scholar
• Goede V, Fischer K, Busch R, et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med 2014;370(12):1101-10
   PubMed Web of Science ®Google Scholar
• Goede V, Fischer K, Engelke A, et al. Obinutuzumab as frontline treatment of chronic lymphocytic leukemia: updated results of the CLL11 study. Leukemia 2015;29(7):1602-4
   PubMed Web of Science ®Google Scholar
• Paper: Preliminary safety results from the phase IIIb GREEN study of obinutuzumab (GA101) alone or in combination with chemotherapy for previously untreated or relapsed/refractory chronic lymphocytic leukemia (CLL) [Internet]. Available from: https://ash.confex.com/ash/2014/webprogram/Paper69476.html [Last accessed 10 Aug 2015]
   Google Scholar
• Cheson BD, Rummel MJ. Bendamustine: rebirth of an old drug. J Clin Oncol 2009;27(9):1492-501
   PubMed Web of Science ®Google Scholar
• Cheson BD, Chua N, Mayer J, et al. Primary results from the Phase III FADOLIN study of obinutuzumab plus bendamustine versus bendamustine alone in rituximab-refractory indolent non-Hodgkin lymphoma. Hematol Oncol 2015;33(suppl 1):167. abstract 123
   Google Scholar
• A study of obinutuzumab + bendamustine in patients with previously untreated chronic lymphocytic leukemia - full text view - clinicaltrials.gov [Internet]. Available from: https://clinicaltrials.gov/ct2/show/NCT02320487
   Google Scholar
• A study evaluating the efficacy of obinutuzumab and bendamustine treatment in patients with refractory or relapsed chronic lymphocytic leukemia - full text view - ClinicalTrials.gov [Internet]. Available from: https://clinicaltrials.gov/ct2/show/NCT02071225 [Last accessed 29 June 2015]
   Google Scholar
• De Romeuf C, Dutertre CA, Le Garff-Tavernier M, et al. Chronic lymphocytic leukaemia cells are efficiently killed by an anti-CD20 monoclonal antibody selected for improved engagement of FcgammaRIIIA/CD16. Br J Haematol 2008;140(6):635-43
   PubMed Web of Science ®Google Scholar
• Le Garff-Tavernier M, Decocq J, de Romeuf C, et al. Analysis of CD16+CD56dim NK cells from CLL patients: evidence supporting a therapeutic strategy with optimized anti-CD20 monoclonal antibodies. Leukemia 2011;25(1):101-9
   PubMed Web of Science ®Google Scholar
• A Phase I trial of ublituximab (TG-1101), a novel glycoengineered anti-CD20 monoclonal antibody (mAb) in B-cell non-Hodgkin lymphoma patients with prior exposure to rituximab. J Clin Oncol [Internet]. Available from: http://meetinglibrary.asco.org/content/132641-144 [Last accessed 2 Jun 2015]
   Google Scholar
• Sharman JP, Farber CM, Mahadevan D, et al. Ublituximab (TG-1101), a Novel Glycoengineered Anti-CD20 Monoclonal Antibody, in Combination with Ibr. 56th ASH annual meeting and exposition. CA, USA, 2014
   Google Scholar
• Ublituximab in combination with ibrutinib versus ibrutinib alone in patients with previously treated high-risk chronic lymphocytic leukemia (CLL) - Full Text View - ClinicalTrials.gov [Internet]. Available from: https://clinicaltrials.gov/ct2/show/NCT02301156 [Last accessed 29 June 2015]
   Google Scholar
• Wiestner A. Emerging role of kinase-targeted strategies in chronic lymphocytic leukemia. Hematology Am Soc Hematol Educ Program 2012;2012:88-96
   PubMedGoogle Scholar
• Chao DT, Korsmeyer SJ. BCL-2 family: regulators of cell death. Annu Rev Immunol 1998;16:395-419
   PubMed Web of Science ®Google Scholar
• Souers AJ, Leverson JD, Boghaert ER, et al. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med 2013;19(2):202-8
   PubMed Web of Science ®Google Scholar
• O’Brien S, Furman RR, Coutre SE, et al. Ibrutinib as initial therapy for elderly patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: an open-label, multicentre, phase 1b/2 trial. Lancet Oncol 2014;15(1):48-58
   PubMed Web of Science ®Google Scholar
• Byrd JC, Furman RR, Coutre SE, et al. Three-year follow-up of treatment-naïve and previously treated patients with CLL and SLL receiving single-agent ibrutinib. Blood 2015;125(16):2497-506
   PubMed Web of Science ®Google Scholar
• Burger JA, Keating MJ, Wierda WG, et al. Safety and activity of ibrutinib plus rituximab for patients with high-risk chronic lymphocytic leukaemia: a single-arm, phase 2 study. Lancet Oncol 2014;15(10):1090-9
   PubMed Web of Science ®Google Scholar
• Furman RR, Sharman JP, Coutre SE, et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med 2014;370(11):997-1007
   PubMed Web of Science ®Google Scholar
• Badoux XC, Keating MJ, Wen S, et al. Phase II study of lenalidomide and rituximab as salvage therapy for patients with relapsed or refractory chronic lymphocytic leukemia. J Clin Oncol 2013;31(5):584-91
   PubMed Web of Science ®Google Scholar
• ABT-199 (GDC-0199) in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL): High complete- response rate and durable disease control. J Clin Oncol [Internet]. Available from: http://meetinglibrary.asco.org/content/134145-144 [Last accessed 13 August 2015]
   Google Scholar
• ABT-199 (GDC-0199) combined with rituximab (R) in patients (pts) with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL): Interim results of a phase 1b study. J Clin Oncol [Internet]. Available from: http://meetinglibrary.asco.org/content/132375-144 [Last accessed 13 August 2015]
   Google Scholar
• Kohrt HE, Sagiv-Barfi I, Rafiq S, et al. Ibrutinib antagonizes rituximab-dependent NK cell–mediated cytotoxicity. Blood 2014;123(12):1957-60
   PubMed Web of Science ®Google Scholar
• Borge M, Belén Almejún M, et al. Ibrutinib impairs the phagocytosis of rituximab-coated leukemic cells from chronic lymphocytic leukemia patients by human macrophages. Haematologica 2015;100(4):e140-2
   PubMed Web of Science ®Google Scholar
• Ibrutinib and rituximab compared with fludarabine phosphate, cyclophosphamide, and rituximab in treating patients with untreated chronic lymphocytic leukemia or small lymphocytic lymphoma - full text view-clinicaltrials.gov [Internet]. Available from: https://clinicaltrials.gov/ct2/show/NCT02048813 [Last accessed 29 June 2015]
   Google Scholar
• Rituximab and bendamustine hydrochloride, rituximab and ibrutinib, or ibrutinib alone in treating older patients with previously untreated chronic lymphocytic leukemia - full text view - clinicaltrials.gov [Internet]. Available from: https://clinicaltrials.gov/ct2/show/NCT01886872 [Last accessed 29 June 2015]
   Google Scholar
• A randomized, double-blind and placebo-controlled study of idelalisib in combination with bendamustine and rituximab for previously treated chronic lymphocytic leukemia (CLL) - Full Text View-ClinicalTrials.gov [Internet]. Available from: https://clinicaltrials.gov/ct2/show/NCT01569295 [Last accessed 29 June 2015]
   Google Scholar
• Press Announcements - FDA issues draft guidance on biosimilar product development [Internet]. Available from: www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm291232.htm [Last accessed 28 June 2015]
   Google Scholar
• Böttcher S, Ritgen M, Fischer K, et al. Minimal residual disease quantification is an independent predictor of progression-free and overall survival in chronic lymphocytic leukemia: a multivariate analysis from the randomized GCLLSG CLL8 trial. J Clin Oncol 2012;30(9):980-8
   PubMed Web of Science ®Google Scholar
• Strati P, Keating MJ, O’Brien SM, et al. Eradication of bone marrow minimal residual disease may prompt early treatment discontinuation in CLL. Blood 2014;123(24):3727-32
   PubMed Web of Science ®Google Scholar