Obinutuzumab plus Chlorambucil in Patients with CLL and Coexisting Conditions

Goede, Valentin; Fischer, Kirsten; Busch, Raymonde; Engelke, Anja; Eichhorst, Barbara; Wendtner, Clemens‐Martin; Chagorova, Tatiana; Serna, Javier de la; Dilhuydy, Marie-Sarah; Illmer, Thomas; Opat, Stephen; Owen, Carolyn; Samoylova, Olga; Kreuzer, Karl‐Anton; Stilgenbauer, Stephan; Döhner, Hartmut; Langerak, Anton W.; Ritgen, Matthias; Kneba, Michael; Asikanius, Elina; Humphrey, Kathryn; Wenger, Michael; Hallek, Michael

doi:10.1056/nejmoa1313984

Cited by 1,350 publications

(1,313 citation statements)

References 39 publications

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“…Together with the novel anti-CD20 obinutuzumab [152] and other promising agents (the BCL2 inhibitor ABT-199 [153], the XPO1 inhibitor selinexor [154], CD47 agonist [155]), these treatments may exert different pressure on CLL clonal evolution and may modify prognostic stratification and evolutionary trajectories, as evaluated until now.…”

Section: Discussionmentioning

confidence: 99%

Chronic lymphocytic leukemia: Time to go past genomics?

2016

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Recent advances in massively parallel sequencing technologies have provided a detailed picture of the mutational landscape in CLL and underscored the vast degree of interpatient and intratumor heterogeneities. These studies have led to the characterization of novel putative driver genes and recurrently affected biological pathways, and to the modeling of CLL clonal evolution. We herein review selected aspects including recent advances in the biology of CLL and present cellular and biological processes involved in the development of CLL and potentially other mature B-cell lymphoproliferative neoplasms.

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Section: Discussionmentioning

confidence: 99%

Chronic lymphocytic leukemia: Time to go past genomics?

2016

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“…Results from Phase1b/2 trials indicated that all patients with CLL experienced rapid and sustained removal of B cells in the peripheral blood. 116-119 In Phase 3 trials, GA101 in combination with chlorambucil prolonged overall survival significantly, as well as progression-free survival and increased the complete response rate 120 . In addition, this combination resulted in substantially increased time to next treatment 121 …”

Section: Therapeutic Afucosylated Antibody Drugs Approved For Market mentioning

confidence: 99%

The “less-is-more” in therapeutic antibodies: Afucosylated anti-cancer antibodies with enhanced antibody-dependent cellular cytotoxicity

Pereira

Chan

Lin

et al. 2018

mAbs

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Therapeutic monoclonal antibodies are the fastest growing class of biological therapeutics for the treatment of various cancers and inflammatory disorders. In cancer immunotherapy, some IgG1 antibodies rely on the Fc-mediated immune effector function, antibody-dependent cellular cytotoxicity (ADCC), as the major mode of action to deplete tumor cells. It is well-known that this effector function is modulated by the N-linked glycosylation in the Fc region of the antibody. In particular, absence of core fucose on the Fc N-glycan has been shown to increase IgG1 Fc binding affinity to the FcγRIIIa present on immune effector cells such as natural killer cells and lead to enhanced ADCC activity. As such, various strategies have focused on producing afucosylated antibodies to improve therapeutic efficacy. This review discusses the relevance of antibody core fucosylation to ADCC, different strategies to produce afucosylated antibodies, and an update of afucosylated antibody drugs currently undergoing clinical trials as well as those that have been approved.

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“…Although these Abs showed better activity in vitro and in xenograft models, 3 results from the present clinical trials are unclear as to whether they are better than rituximab, as these novel Abs were used at an optimized pharmacokinetic schedule, but the rituximab schedule was not pharmacokinetically optimized. 4,5 This suggests novel approaches are urgently needed to improve the efficacy of the current anti-CD20 Ab-based therapies.…”

Section: Introductionmentioning

confidence: 99%