Obinutuzumab in the Treatment of B-cell Malignancies: a Comprehensive Review

Overview

Journal Future Oncol

Specialty Oncology

Date 2022 Jul 20

PMID 35856239

Authors

Andrew Davies

Arnon P Kater

Jeff P Sharman

Stephan Stilgenbauer

Umberto Vitolo

Christian Klein

Joana Parreira

Gilles Salles

Affiliations

Soon will be listed here.

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.

Citing Articles

Obinutuzumab in membranous nephropathy: a potential game-changer in treatment.

Sessa C, Galeano D, Zanoli L, Delsante M, Rossi G, Morale W Drugs Context. 2025; 14.

PMID: 40017729 PMC: 11867167. DOI: 10.7573/dic.2024-9-1.

Efficacy, safety and cost-effectiveness of obinutuzumab in patients with follicular lymphoma: a rapid review.

Wang C, Dong Y, Men P, Zhang R, Xiao Y, Bu Y Front Pharmacol. 2025; 15():1426772.

PMID: 39830356 PMC: 11738910. DOI: 10.3389/fphar.2024.1426772.

Antibody-Based Immunotherapies for the Treatment of Hematologic Malignancies.

Jureczek J, Kalwak K, Dziegiel P Cancers (Basel). 2025; 16(24.

PMID: 39766080 PMC: 11674729. DOI: 10.3390/cancers16244181.

Persistent SARS-CoV-2 infection resolved after B-cell recovery in a patient with follicular lymphoma treated with B-cell depletion therapy.

Sueda Y, Tokuyasu H, Atsuta M, Sakai H, Arai K, Esumi C Respir Med Case Rep. 2024; 52:102131.

PMID: 39507269 PMC: 11538806. DOI: 10.1016/j.rmcr.2024.102131.

Obinutuzumab-Induced Inflammatory Bowel Disease-Like Pancolitis: A First Case Report.

Mendes R, Figueiredo P, Andrade I GE Port J Gastroenterol. 2024; 31(4):278-282.

PMID: 39114324 PMC: 11305687. DOI: 10.1159/000533499.

References

Pavlasova G, Mraz M . The regulation and function of CD20: an "enigma" of B-cell biology and targeted therapy. Haematologica. 2020; 105(6):1494-1506. PMC: 7271567. DOI: 10.3324/haematol.2019.243543. View

Patz M, Isaeva P, Forcob N, Muller B, Frenzel L, Wendtner C . Comparison of the in vitro effects of the anti-CD20 antibodies rituximab and GA101 on chronic lymphocytic leukaemia cells. Br J Haematol. 2010; 152(3):295-306. DOI: 10.1111/j.1365-2141.2010.08428.x. View

Davis T, Czerwinski D, Levy R . Therapy of B-cell lymphoma with anti-CD20 antibodies can result in the loss of CD20 antigen expression. Clin Cancer Res. 1999; 5(3):611-5. View

Leblond V, Aktan M, Ferra Coll C, Dartigeas C, Kisro J, Montillo M . Safety of obinutuzumab alone or combined with chemotherapy for previously untreated or relapsed/refractory chronic lymphocytic leukemia in the phase IIIb GREEN study. Haematologica. 2018; 103(11):1889-1898. PMC: 6278964. DOI: 10.3324/haematol.2017.186387. View

McLaughlin P, Grillo-Lopez A, Link B, Levy R, Czuczman M, Williams M . 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. DOI: 10.1200/JCO.1998.16.8.2825. View

Kos I, Balensiefer B, Roth S, Ahlgrimm M, Sester M, Schmidt T . Prolonged Course of COVID-19-Associated Pneumonia in a B-Cell Depleted Patient After Rituximab. Front Oncol. 2020; 10:1578. PMC: 7493633. DOI: 10.3389/fonc.2020.01578. View

Soumerai J, Mato A, Dogan A, Seshan V, Joffe E, Flaherty K . Zanubrutinib, obinutuzumab, and venetoclax with minimal residual disease-driven discontinuation in previously untreated patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: a multicentre, single-arm, phase 2 trial. Lancet Haematol. 2021; 8(12):e879-e890. PMC: 9326222. DOI: 10.1016/S2352-3026(21)00307-0. View

Polyak M, Li H, Shariat N, Deans J . CD20 homo-oligomers physically associate with the B cell antigen receptor. Dissociation upon receptor engagement and recruitment of phosphoproteins and calmodulin-binding proteins. J Biol Chem. 2008; 283(27):18545-52. DOI: 10.1074/jbc.M800784200. View

Hallek M, Fischer K, Fingerle-Rowson G, Fink A, Busch R, Mayer J . 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. DOI: 10.1016/S0140-6736(10)61381-5. View

10.

Huber H, Edenhofer S, von Tresckow J, Robrecht S, Zhang C, Tausch E . Obinutuzumab (GA-101), ibrutinib, and venetoclax (GIVe) frontline treatment for high-risk chronic lymphocytic leukemia. Blood. 2022; 139(9):1318-1329. DOI: 10.1182/blood.2021013208. View

11.

Woyach J, Ruppert A, Heerema N, Zhao W, Booth A, Ding W . Ibrutinib Regimens versus Chemoimmunotherapy in Older Patients with Untreated CLL. N Engl J Med. 2018; 379(26):2517-2528. PMC: 6325637. DOI: 10.1056/NEJMoa1812836. View

12.

Zappasodi R, De Braud F, Di Nicola M . Lymphoma Immunotherapy: Current Status. Front Immunol. 2015; 6:448. PMC: 4555084. DOI: 10.3389/fimmu.2015.00448. View

13.

Rouge L, Chiang N, Steffek M, Kugel C, Croll T, Tam C . Structure of CD20 in complex with the therapeutic monoclonal antibody rituximab. Science. 2020; 367(6483):1224-1230. DOI: 10.1126/science.aaz9356. View

14.

Sehn L, Chua N, Mayer J, Dueck G, Trneny M, Bouabdallah K . Obinutuzumab plus bendamustine versus bendamustine monotherapy in patients with rituximab-refractory indolent non-Hodgkin lymphoma (GADOLIN): a randomised, controlled, open-label, multicentre, phase 3 trial. Lancet Oncol. 2016; 17(8):1081-1093. DOI: 10.1016/S1470-2045(16)30097-3. View

15.

Herter S, Herting F, Mundigl O, Waldhauer I, Weinzierl T, Fauti T . Preclinical activity of the type II CD20 antibody GA101 (obinutuzumab) compared with rituximab and ofatumumab in vitro and in xenograft models. Mol Cancer Ther. 2013; 12(10):2031-42. DOI: 10.1158/1535-7163.MCT-12-1182. View

16.

Sharman J, Egyed M, Jurczak W, Skarbnik A, Pagel J, Flinn I . Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzmab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): a randomised, controlled, phase 3 trial. Lancet. 2020; 395(10232):1278-1291. PMC: 8151619. DOI: 10.1016/S0140-6736(20)30262-2. View

17.

Seymour J, Kipps T, Eichhorst B, Hillmen P, DRozario J, Assouline S . Venetoclax-Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia. N Engl J Med. 2018; 378(12):1107-1120. DOI: 10.1056/NEJMoa1713976. View

18.

Pott C, Sehn L, Belada D, Gribben J, Hoster E, Kahl B . MRD response in relapsed/refractory FL after obinutuzumab plus bendamustine or bendamustine alone in the GADOLIN trial. Leukemia. 2019; 34(2):522-532. PMC: 7214251. DOI: 10.1038/s41375-019-0559-9. View

19.

Burger J, Sivina M, Jain N, Kim E, Kadia T, Estrov Z . Randomized trial of ibrutinib vs ibrutinib plus rituximab in patients with chronic lymphocytic leukemia. Blood. 2018; 133(10):1011-1019. PMC: 6405333. DOI: 10.1182/blood-2018-10-879429. View

20.

Robak T, Robak E . New anti-CD20 monoclonal antibodies for the treatment of B-cell lymphoid malignancies. BioDrugs. 2010; 25(1):13-25. DOI: 10.2165/11539590-000000000-00000. View