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Review
. 2022 Aug;18(26):2943-2966.
doi: 10.2217/fon-2022-0112. Epub 2022 Jul 20.

Obinutuzumab in the treatment of B-cell malignancies: a comprehensive review

Andrew Davies  1 , Arnon P Kater  2 , Jeff P Sharman  3 , Stephan Stilgenbauer  4 , Umberto Vitolo  5 , Christian Klein  6 , Joana Parreira  7 , Gilles Salles  8
Affiliations
Review

Obinutuzumab in the treatment of B-cell malignancies: a comprehensive review

Andrew Davies et al. Future Oncol. 2022 Aug.

Abstract

The type II anti-CD20 antibody obinutuzumab has structural and mechanistic features that distinguish it from the first anti-CD20 antibody, rituximab, which have translated into improved efficacy in phase III trials in indolent non-Hodgkin lymphoma and chronic lymphocytic leukemia (CLL). These gains have been shown through improvements in, and/or increased durability of, tumor response, and increases in progression-free survival in patients with CLL or follicular lymphoma (FL). Ongoing research is focusing on the use of biomarkers and the development of chemotherapy-free regimens involving obinutuzumab. phase II trials of such treatment regimens have shown promise for CLL, FL and mantle cell lymphoma, while phase III trials have highlighted obinutuzumab as the antibody partner of choice for novel agents in first-line CLL treatment.

Keywords: B-cell malignancies; CLL; DLBCL; FL; anti-CD20; antibody; obinutuzumab.

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Conflict of interest statement

A Davies declares Celgene (Research Funding, Advisory Board, Honorarium, Other: travel to scientific conferences); Roche (Advisory Board, Honorarium, Research Support, Other: travel to scientific conferences); Gilead/Kite Pharma (Advisory Boards, Honorarium, Research Support); Takeda (Advisory Boards, Honorarium, Research Support); Janssen (Honorarium, Research Support); Kayropharma (Advisory Board, Research Support); Acerta Pharma (Research Support, Honorarium); AstraZeneca (Research Support, Honorarium); ADC Therapeutics (Research Support, Honorarium); Incyte (Advisory Board attendance, Honorarium); VelosBio (Advisory Board attendance, Honorarium). AP Kater declares personal fees and research support from Genentech, Roche, and AbbVie; Research Support from Janssen; Consultancy fees from AbbVie, Genentech, Roche, BMS, Astra Zeneca, Janssen, and Lava; Teaching Support from AbbVie. JP Sharman declares personal fees from AbbVie, Acerta Pharma (a member of the AstraZeneca Group), AstraZeneca, Genentech, Pharmacyclics, Sunesis, and TG Therapeutics. S Stilgenbauer declares Advisory Board fees, Research Support, Travel Support, and Speaker fees from AbbVie, Amgen, AstraZeneca, BeiGene, BMS, Celgene, Gilead, GSK, Roche, Janssen, Novartis, Sunesis. U Vitolo declares Roche (Honorarium, Advisory role, Speakers’ bureau); Janssen (Honorarium, Advisory role, Speakers’ bureau); Celgene (Honorarium, Advisory role, Speakers’ bureau, Research Support); Mundipharma (Honorarium, Speakers’ bureau). C Klein declares employment, patents & royalties and stock ownership with Roche. J Parreira declares employment, honorarium and stock ownership with Roche. G Salles research was funded in part through the NIH/NCI Cancer Center support grant P30 CA008748; G Salles declares consulting fees from Morphosys, Incyte, Novartis, Epizyme; honorarium from Abbvie, BMS/Celgene, Epizyme, Janssen, Regeneron, Bayer; Advisory Board fees from Beigene, Epizyme, Genentech/Roche, Genmab, Janssen, Incyte, Gilead/Kite, Miltenyi, Morphosys, Novartis, Velosbio, Takeda, Rapt, Loxo. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Third-party medical writing assistance, under the direction of the authors was provided by A Lynch and E Lynch of Ashfield MedComms, an Inizio company, and was funded by F Hoffmann-La Roche Ltd.

Figures

Figure 1.
Figure 1.. Mechanism of action of type I and type II anti-CD20 monoclonal antibodies.
Adapted from [22,25] with permission from Taylor & Francis Group. ADCC: Antibody-dependent cell-mediated cytotoxicity; ADCP: Antibody-dependent cell-mediated phagocytosis; CDC: Complement-dependent cytotoxicity.
Figure 2.
Figure 2.. Progression-free survival with obinutuzumab-chlorambucil versus chlorambucil, andobinutuzumab-chlorambucil versus rituximab-chlorambucil, in the phase III CLL11 study in patients with previously untreated chronic lymphocytic leukemia.
(A) G-Clb versus Clb. (B) G-Clb versus R-Clb. Clb: Chlorambucil; CLL: Chronic lymphocytic leukemia; G: Obinutuzumab; HR: Hazard ratio; PFS: Progression-free survival; R: Rituximab.
Figure 3.
Figure 3.. Progression-free survival with obinutuzumab-venetoclax versus obinutuzumab-chlorambucil in the phase III CLL14 study in patients with previously untreated chronic lymphocytic leukemia.
HR: Hazard ratio; PFS: Progression-free survival.
Figure 4.
Figure 4.. Progression-free survival with rituximab-chemotherapy versus obinutuzumab-chemotherapy in the phase III GALLIUM study in patients with previously untreated advanced follicular lymphoma.
HR: Hazard ratio; PFS: Progression-free surviva.
Figure 5.
Figure 5.. Progression-free survival with rituximab-cyclophosphamide, doxorubicin, vincristine and prednisone chemotherapyversus obinutuzumab-cyclophosphamide, doxorubicin, vincristine and prednisone chemotherapyin the phase III GOYA study in patients with previously untreated diffuse large B-cell lymphoma.
CHOP: Cyclophosphamide, doxorubicin, vincristine and prednisone chemotherapy; HR: Hazard ratio; PFS: Progression-free survival.
See this image and copyright information in PMC

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