COMPARISON IMMUNOCHEMOTHERAPY AND CHEMOTHERAPY EFFICASY IN FOLLICULAR LYMPHOMA

Introduction. Immunochemotherapy is an obligate component in treatment of follicular lymphoma (FL). Monoclonal antibodies to CD20 antigen is the most well studied and frequently used drug. Chemotherapy department of Russian Cancer Research Center has a very good experience in FL treatment using rituximab. In the article we characterize and compare two methods of treatment of FL - polychemotherapy vs chemotherapy. Materials and methods. 286 patients with FL were included into analysis. In 125 (44 %) from 286 patients polychemotherapy was used as a first line of FL treatment. In 161 (56 %) patients rituximab was added to chemothrepy regimens. Analysis of survival and disease-free survival was done according to Kaplan-Meier. Analysis of treatment results has been done according to international criteria of treatment response in non-Hodgkin’s lymphomas. In statistical calculations SPSS program for Windows was used. Results. Responses to treatment were significantly better in immunochemotherapy group of patients, p = 0,002. In unifactorial analysis rituximab significantly improved both overall and disease-free sirvival. Taking in mind that groups of patients receiving chemotherapy and immunochemotherapy were not completely identical we performed multifactorial analysis, Coxs regression analysis. In that case (Cox regression analysis) significant advantages of immunochemotherapy were noted in improving disease-free survival in FL patients (р = 0,000); significant influence on overall survival was not noted (p = 0,44). Addition of rituximab did not improved overall and disease-free survival in a group (n = 88; 31 %) of refractory and early relapsing FL. Conclusion. Addition of rituximab to polychemotherapy in FL patients significantly improved treatment results. In multifactorial analysis immunochemotherapy was the most important prognostic factors of favourable prognosis of disease-free survival. In that analysis rituximab did not influenced on overall survival and on survival in refractory and early relapsing FL.

ритуксимаб, фолликулярная лимфома, полихимиотерапия, иммунохимиотерапия, rituximab, follicular lymphoma, polychemotherapy, immunochemotherapy

1. Singh V., Gupta D., 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 Ther 2015; 7(11): 347-58. DOI: 10.4172/1948-5956.1000373. PMID: 27413424. PMCID: PMC4939752.

2. Pfreundschuh M., Trumper L., Osterborg A. et al. MabThera International Trial, CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. The Lancet. Oncology 2006; 7(5): 379-91. DOI: 10.1016/S1470-2045(06)70664-7. PMID: 16648042.

3. McLaughlin P., Grillo Lopez A.J., Link B.K. et al. 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. PMID: 9704735.

4. Davis T.A., White C.A., Grillo-López A.J. et al. Single-agent monoclonal antibody efficacy in bulky non-Hodgkin’s lymphoma: results of a phase II trial of rituximab. J Clin Oncol 1999; 17(6): 1851-7. DOI: 10.1200/jco.1999.17.6.1851. PMID: 10561225.

5. Foran J.M., Gupta R.K., Cunningham D. et al. A UK multicentre phase II study of rituximab (chimaeric anti-CD20 monoclonal antibody) in patients with follicular lymphoma, with PCR monitoring of molecular response. Br J Haematol 2000; 109(1): 81-8. PMID: 10848785.

6. Hainsworth J.D., Litchy S., Shaffer D.W. et al. Maximizing therapeutic benefit of rituximab: maintenance therapy versus re-treatment at progression in patients with indolent non-Hodgkin’s lymphoma a randomized phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol 2005; 23(6): 1088-95. DOI: 10.1200/JCO.2005.12.191. PMID: 15657401.

7. Hiddemann W., Kneba M., Dreyling M. et al. Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood 2005; 106(12): 3725-32. DOI: 10.1182/blood-2005-01-0016. PMID: 16123223.

8. Herold M., Haas A., Srock S. et al. Rituximab added to first-line mitoxantrone, chlorambucil, and prednisolone chemotherapy followed by interferon maintenance prolongs survival in patients with advanced follicular lymphoma: an East German Study Group Hematology and Oncology Study. J Clin Oncol 2007; 25(15): 1986-92. DOI: 10.1200/JCO.2006.06.4618. PMID: 17420513.

9. Marcus R., Imrie K., Solal-Celigny P. et al. Phase III study of R-CVP compared with cyclophosphamide, vincristine, and prednisone alone in patients with previously untreated advanced follicular lymphoma. J Clin Oncol 2008; 26(28): 4579-86. DOI: 10.1200/JCO.2007.13.5376. PMID: 18662969.

10. Salles G., Mounier N., De Guibert S. et al. Rituximab combined with chemotherapy and interferon in follicular lymphoma patients: results of the GELA-GOELAMS FL2000 study. Blood 2008; 112(13): 4824-31. DOI: 10.1182/blood-2008-04-153189. PMID: 18799723.

11. Swerdlow S.H., Campo E., Harris N.L. et al. (Eds.) WHO classification of tumours of haematopoietic and lymphoid tissues. WHO Press, 2008.

12. Cheson B.D., Horning S.J., Coiffier B. et al. Report of an international workshop to standardize response criteria for non-Hodgkin’s lymphomas. NCI Sponsored International Working Group. J Clin Oncol 1999; 17(4): 1244. DOI: 10.1200/jco.1999.17.4.1244. PMID: 10561185.

13. Armitage J.O., Weisenburger D.D. New approach to classifying non-Hodgkin’s lymphomas: clinical features of the major histologic subtypes. Non-Hodgkin’s Lymphoma Classification Project. J Clin Oncol 1998; 16: 2780-95. DOI: 10.1200/jco.1998.16.8.2780. PMID: 9704731.

14. Horning S.J., Rosenberg S.A. The natural history of initially untreated low-grade non-Hodgkin’s lymphomas. N Engl J Med 1984; 311(23): 1471-75. DOI: 10.1056/NEJM198412063112303. PMID: 6548796.

15. Friedberg J.W., Taylor M.D., Cerhan J.R. et al. Follicular lymphoma in the United States: first report of the national LymphoCare study. J Clin Oncol 2009; 27(8): 1202-08. DOI: 10.1200/JCO.2008.18.1495. PMID: 19204203. PMCID: PMC2738614.

16. Marcus R., Imrie K., Belch A. et al. CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Blood 2005; 105(4): 1417-23. DOI: 10.1182/blood-2004-08-3175. PMID: 15494430.

17. Forstpointner R., Dreyling M., Repp R. et al. The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone [FCM] significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood 2004; 104(10): 3064-71. DOI: 10.1182/blood-2004-04-1323. PMID: 15284112.

18. Murakami S., Kato H., Higuchi Y. et al. Prediction of high risk for death in patients with follicular lymphoma receiving rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in first-line chemotherapy. J Ann Hematol 2016; 95(8): 1259-69. DOI: 10.1007/s00277-016-2690-2. PMID: 27220639.

19. Rummel M.J., Niederle N., Maschmeyer G. et al. Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: An open-label, multicentre, randomised, phase 3 non-inferiority trial. Lancet 2013; 381(9873): 1203-10. DOI: 10.1016/S0140-6736(12)61763-2. PMID: 23433739.

20. Salles G., Seymour J.F., Offner F. et al. 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. Lancet 2011; 377 (9759): 42-51. DOI: 10.1016/S0140-6736(10)62175-7. PMID: 21176949.

21. Fisher R.I., LeBlanc M., Press O.W. et al. New treatment options have changed the survival of patients with follicular lymphoma. J Clin Oncol 2005; 23(33): 8447-52. DOI: 10.1200/JCO.2005.03.1674. PMID: 16230674.

22. Dave S.S., Wright G., Tan B. et al. Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells. N Engl J Med 2004; 351: 2159-69. DOI: 10.1056/NEJMoa041869. PMID: 15548776.