Clinical significance of the loss of CD20 antigen on tumor cells in patients with relapsed or refractory follicular lymphoma

Jean-Marie Michot , Alice Buet-Elfassy , Maxime Annereau , Julien Lazarovici , Alina Danu , Clémentine Sarkozy , Claude Chahine , Camille Bigenwald , Jacques Bosq , Julien Rossignol , Patricia Romano-Martin , Capucine Baldini , David Ghez , Peggy Dartigues , Christophe Massard , Vincent Ribrag

Cancer Drug Resistance ›› 2021, Vol. 4 ›› Issue (3) : 710 -8.

PDF
Cancer Drug Resistance ›› 2021, Vol. 4 ›› Issue (3) :710 -8. DOI: 10.20517/cdr.2020.109
review-article

Clinical significance of the loss of CD20 antigen on tumor cells in patients with relapsed or refractory follicular lymphoma

Author information +
History +
PDF

Abstract

Aim: Anti-CD20 monoclonal antibody is a cornerstone therapy for follicular lymphoma. Following anti-CD20 therapy, a potential decrease in CD20 antigen, and therefore a loss of the tumor target might be expected. However, the incidence and clinical significance of CD20 loss on tumor cells in patients with relapsed or refractory follicular lymphoma are unknown. This study aims to investigate the incidence and outcome of patients with relapsed or refractory follicular lymphoma patients harboring the loss of the tumor target, CD20.

Methods: All consecutive adult patients with relapsed or refractory follicular lymphoma referred to the Early Drug Department at Gustave Roussy were included. The main objectives were to assess the incidence and prognosis of the loss in expression of CD20 antigen on the surface of tumor cells on patient outcome.

Results: Over the study period 2013-2018, 131 patients were screened for clinical trials with B-cell malignancies in the early drug department of Gustave Roussy in France. Forty-four patients presented with relapsed or refractory follicular lymphoma and 32 had tumor biopsies at the time of relapse that were retained for analysis. The median (range) age was 67.5 years (55.3-75.3) and the median number of prior anti-cancer systemic therapies was 3 (2-4). At the time of relapse, CD20 expression was positive in 84% of tumors (n = 27) and negative in 16% of tumors (n = 5). At a median follow-up of 18.3 (0.6-83.3) months, CD20 negativity was associated with a poorer prognosis with a median overall survival of 8.9 months (95%CI: 2.4-19.1) in comparison to CD20 positive patients (28.3 months, 95%CI: 25.1-75.3 months, P = 0.019).

Conclusion: The loss of the tumor target antigen, CD20, occurred in 16% of patients with relapse or refractory follicular lymphoma. Due to confounding factors in patients who received anti-CD20 immunotherapy, it was not possible to formally establish the prognostic significance of CD20 negativity. However, we suggest that a check for CD20 antigen positivity nevertheless be performed to adapt subsequent therapies for patients with relapsed or refractory follicular lymphoma.

Keywords

Follicular lymphoma / CD20 tumor antigen / anti-CD20 monoclonal antibody / cancer drug resistance

Cite this article

Download citation ▾
Jean-Marie Michot, Alice Buet-Elfassy, Maxime Annereau, Julien Lazarovici, Alina Danu, Clémentine Sarkozy, Claude Chahine, Camille Bigenwald, Jacques Bosq, Julien Rossignol, Patricia Romano-Martin, Capucine Baldini, David Ghez, Peggy Dartigues, Christophe Massard, Vincent Ribrag. Clinical significance of the loss of CD20 antigen on tumor cells in patients with relapsed or refractory follicular lymphoma. Cancer Drug Resistance, 2021, 4(3): 710-8 DOI:10.20517/cdr.2020.109

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Molina A.A decade of Rituximab: Improving survival outcomes in non-Hodgkin’s lymphoma.Annu Rev Med2008;59:237-50

[2]

Morschhauser F,Feugier P.Rituximab plus Lenalidomide in advanced untreated follicular lymphoma.N Engl J Med2018;379:934-47

[3]

Salles G,Offner F.Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial.Lancet2011;377:42-51

[4]

Singh V,Almasan A.Development of novel anti-Cd20 monoclonal antibodies and modulation in Cd20 levels on cell surface: Looking to improve immunotherapy response.J Cancer Sci Ther2015;7:347-58 PMCID:PMC4939752

[5]

Hiraga J,Sugimoto T.Down-regulation of CD20 expression in B-cell lymphoma cells after treatment with rituximab-containing combination chemotherapies: its prevalence and clinical significance.Blood2009;113:4885-93

[6]

Jilani I.Transient down-modulation of CD20 by rituximab in patients with chronic lymphocytic leukemia.Blood2003;102:3514-20

[7]

Cartron G,Salles G.Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcgammaRIIIa gene.Blood2002;99:754-8

[8]

Haidar JH,Salem Z.Loss of CD20 expression in relapsed lymphomas after rituximab therapy.Eur J Haematol2003;70:330-2

[9]

Bagacean C,Ianotto JC.CD20 negative relapse of a follicular lymphoma after chemoimmunotherapy.HVM Bioflux 2015;7:302-5

[10]

Álvaro-Naranjo T,Gumá-Padró J.CD20-negative DLBCL transformation after rituximab treatment in follicular lymphoma: a new case report and review of the literature.Ann Hematol2003;82:585-8

[11]

Davis TA,Levy R.Therapy of B-cell lymphoma with anti-CD20 antibodies can result in the loss of CD20 antigen expression.Clin Cancer Res1999;5:611-5

[12]

Swerdlow SH,Pileri SA.The 2016 revision of the World Health Organization classification of lymphoid neoplasms.Blood2016;127:2375-90 PMCID:PMC4874220

[13]

Foran JM,Micallef INM.Loss of CD20 expression following treatment with rituximab (chimaeric monoclonal anti-CD20): a retrospective cohort analysis.Br J Haematol2001;114:881-3

[14]

Maeshima A,Fukuhara S.Follow-up data of 10 patients with B-cell non-Hodgkin lymphoma with a CD20-negative phenotypic change after rituximab-containing therapy.Am J Surg Pathol2013;37:563-70

[15]

Czuczman MS,Gowda A.Acquirement of rituximab resistance in lymphoma cell lines is associated with both global CD20 gene and protein down-regulation regulated at the pretranscriptional and posttranscriptional levels.Clin Cancer Res2008;14:1561-70

[16]

Johnson NA,Woolcock B.CD20 mutations involving the rituximab epitope are rare in diffuse large B-cell lymphomas and are not a significant cause of R-CHOP failure.Haematologica2009;94:423-7 PMCID:PMC2649361

[17]

Tsutsumi Y,Ito S.5-Azacytidine partially restores CD20 expression in follicular lymphoma that lost CD20 expression after rituximab treatment: a case report.J Med Case Reports2016;10:27 PMCID:PMC4739428

[18]

Chow VA,Gopal AK.Translating anti-CD19 CAR T-cell therapy into clinical practice for relapsed/refractory diffuse large B-cell lymphoma.Blood2018;132:777-81 PMCID:PMC6107879

[19]

Morschhauser F,Advani R.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 Haematol2019;6:e254-65

[20]

Bukhari A.Blinatumomab: a novel therapy for the treatment of non-Hodgkin’s lymphoma.Expert Rev Hematol2019;12:909-18

[21]

Hiddemann W,Canales MA.Immunochemotherapy with Obinutuzumab or Rituximab for previously untreated follicular lymphoma in the GALLIUM study: influence of chemotherapy on efficacy and safety.J Clin Oncol2018;36:2395-404

[22]

Morschhauser F,Feugier P.Obinutuzumab combined with lenalidomide for relapsed or refractory follicular B-cell lymphoma (GALEN): a multicentre, single-arm, phase 2 study.Lancet Haematol2019;6:e429-37

AI Summary AI Mindmap
PDF

108

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/