The anti-CD79b ADC pola has shown promising activity in relapsed/refractory DLBCL and FL, and is currently FDA-approved in combination with bendamustine and rituximab in patients with relapsed/refractory DLBCL after at least two prior therapies. Myelosuppression and peripheral neuropathy are the main toxicities of pola. Pola has also shown encouraging preliminary results when combined with R-CHP in patients with previously untreated DLBCL and the results of the phase 3 trial of pola plus R-CHP vs R-CHOP will define if it has a role in the frontline treatment of DLBCL. Pola’s role in FL is less clear at this point as the combinations studied so far have failed to show a benefit over approved therapies. Given the wide expression of its target (CD79b), unique mechanism of action, and good safety profile, pola is a suitable candidate for combination studies in B-cell NHL. The results of ongoing clinical trials to confirm pola’s efficacy and investigate other potential combinations are eagerly awaited.


The authors report no conflicts of interest in this work.

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Yazeed Sawalha, Kami Maddocks

Department of Internal Medicine, Division of Hematology, Arthur G. James Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH, USA

Correspondence: Yazeed Sawalha
Department of Internal Medicine, Division of Hematology, The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital, A350B Starling-Loving Hall, 320 W. 10th Ave., Columbus, OH 43210, USA
Tel +1 614-293-0837
Fax +1 614-293-7526
Email [email protected]


1. Dornan D, Bennett F, Chen Y, et al. Therapeutic potential of an anti-CD79b antibody-drug conjugate, anti-CD79b-vc-MMAE, for the treatment of non-Hodgkin lymphoma. Blood. 2009;114(13):2721–2729. doi:10.1182/blood-2009-02-205500

2. Dal Porto JM, Gauld SB, Merrell KT, Mills D, Pugh-Bernard AE, Cambier J. B cell antigen receptor signaling 101. Mol Immunol. 2004;41(6–7):599–613. doi:10.1016/j.molimm.2004.04.008

3. Chu PG, Arber DA. CD79: a review. Appl Immunohistochem Mol Morphol. 2001;9(2):97–106. doi:10.1097/00129039-200106000-00001

4. Polson AG, Yu SF, Elkins K, et al. Antibody-drug conjugates targeted to CD79 for the treatment of non-Hodgkin lymphoma. Blood. 2007;110(2):616–623. doi:10.1182/blood-2007-01-066704

5. Busman-Sahay K, Drake L, Sitaram A, Marks M, Drake JR. Cis and trans regulatory mechanisms control AP2-mediated B cell receptor endocytosis via select tyrosine-based motifs. PLoS One. 2013;8(1):e54938. doi:10.1371/journal.pone.0054938

6. Cabezudo E, Carrara P, Morilla R, Matutes E. Quantitative analysis of CD79b, CD5 and CD19 in mature B-cell lymphoproliferative disorders. Haematologica. 1999;84(5):413–418.

7. D’Arena G, Musto P, Cascavilla N, Dell’Olio M, Di Renzo N, Carotenuto M. Quantitative flow cytometry for the differential diagnosis of leukemic B-cell chronic lymphoproliferative disorders. Am J Hematol. 2000;64(4):275–281. doi:10.1002/1096-8652(200008)64:4<275::aid-ajh7>;2-y

8. Pfeifer M, Zheng B, Erdmann T, et al. Anti-CD22 and anti-CD79B antibody drug conjugates are active in different molecular diffuse large B-cell lymphoma subtypes. Leukemia. 2015;29(7):1578–1586. doi:10.1038/leu.2015.48

9. Fuh FK, Looney C, Li D, et al. Anti-CD22 and anti-CD79b antibody-drug conjugates preferentially target proliferating B cells. Br J Pharmacol. 2017;174(8):628–640. doi:10.1111/bph.13697

10. Schmitz R, Wright GW, Huang DW, et al. Genetics and pathogenesis of diffuse large B-cell lymphoma. N Engl J Med. 2018;378(15):1396–1407. doi:10.1056/NEJMoa1801445

11. Allan JN, Bhavsar EB, Vaisitti T, et al. CD79b expression in Richter’s transformation. Blood. 2019;134(Supplement_1):4279. doi:10.1182/blood-2019-128305

12. Palanca-Wessels MCA, Czuczman M, Salles G, et al. Safety and activity of the anti-CD79B antibody-drug conjugate polatuzumab vedotin in relapsed or refractory B-cell non-Hodgkin lymphoma and chronic lymphocytic leukaemia: a phase 1 study. Lancet Oncol. 2015;16(6):704–715. doi:10.1016/S1470-2045(15)70128-2

13. Morschhauser F, Flinn IW, Advani R, et al. Polatuzumab vedotin or pinatuzumab vedotin plus rituximab in patients with relapsed or refractory non-Hodgkin lymphoma: final results from a phase 2 randomised study (ROMULUS). Lancet Haematol. 2019;6(5):e254–e265. doi:10.1016/S2352-3026(19)30026-2

14. Sehn LH, Herrera AF, Flowers CR, et al. Polatuzumab vedotin in relapsed or refractory diffuse large B-cell lymphoma. J Clin Oncol. 2019;38(2):JCO1900172. doi:10.1200/JCO.19.00172

15. Sehn LH, Kamdar M, Herrera AF, et al. Randomized phase 2 trial of polatuzumab vedotin (pola) with bendamustine and rituximab (BR) in relapsed/refractory (r/r) FL and DLBCL. J Clin Oncol. 2018;36(15_suppl):7507. doi:10.1200/JCO.2018.36.15_suppl.7507

16. Leonard JP, Trneny M, Izutsu K, et al. AUGMENT: a Phase III study of lenalidomide plus rituximab versus placebo plus rituximab in relapsed or refractory indolent lymphoma. J Clin Oncol. 2019;37(14):1188–1199. doi:10.1200/JCO.19.00010

17. Morschhauser F, Fowler NH, Feugier P, et al. Rituximab plus lenalidomide in advanced untreated follicular lymphoma. N Engl J Med. 2018;379(10):934–947. doi:10.1056/NEJMoa1805104

18. Morschhauser F, Le Gouill S, Feugier P, et al. Obinutuzumab combined with lenalidomide for relapsed or refractory follicular B-cell lymphoma (GALEN): a multicentre, single-arm, phase 2 study. Lancet Haematol. 2019;6(8):e429–e437. doi:10.1016/S2352-3026(19)30089-4

19. Fowler NH, Nastoupil LJ, Chin C, et al. A Phase I/II study of lenalidomide plus obinutuzumab in relapsed indolent lymphoma. Blood. 2019;134(Supplement_1):348. doi:10.1182/blood-2019-131045

20. Nastoupil LJ, Westin JR, Hagemeister FB, et al. Results of a Phase II study of obinutuzumab in combination with lenalidomide in previously untreated, high tumor burden follicular lymphoma (FL). Blood. 2019;134(Supplement_1):125. doi:10.1182/blood-2019-129422

21. Diefenbach C, Kahl BS, Banerjee L, et al. Polatuzumab vedotin plus obinutuzumab and lenalidomide in patients with relapsed/refractory follicular lymphoma: primary analysis of the full efficacy population in a Phase Ib/II Trial. Blood. 2019;134(Supplement_1):126. doi:10.1182/blood-2019-123669

22. Tilly H, Morschhauser F, Bartlett NL, et al. Polatuzumab vedotin in combination with immunochemotherapy in patients with previously untreated diffuse large B-cell lymphoma: an open-label, non-randomised, phase 1b–2 study. Lancet Oncol. 2019;20(7):998–1010. doi:10.1016/S1470-2045(19)30091-9

23. Vitolo U, Trneny M, Belada D, et al. Obinutuzumab or rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in previously untreated diffuse large b-cell lymphoma. J Clin Oncol. 2017;35(31):3529–3537. doi:10.1200/JCO.2017.73.3402

24. Genentech Inc. PolivyTM (Polatuzumab vedotin-piiq) for injection, for intravenous use: US Prescribing Information; 2019. Available from: Accessed February 21, 2020.

25. Audino AN, Barth MJ, Tiwari A, et al. Polatuzumab vedotin, an antibody-drug conjugate targeting CD79b, is a highly active agent against burkitt lymphoma and primary mediastinal B-cell lymphoma. Blood. 2019;134(Supplement_1):3963. doi:10.1182/blood-2019-128580

26. Herrera A, Patel M, Burke J, et al. A Phase I study of the anti-CD79b THIOMAB antibody-drug conjugate DCDS0780A in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma. Blood. 2017;130:4140.

Source: OncoTargets and Therapy.
Originally published June 8, 2020.

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