Impact of Inadequate Doses of Rituximab in the Treatment of Diffuse Large B Cell Lymphoma in Malaysian Patients

  • Published : 2014.02.28


Background: The current standard treatment for patients with newly diagnosed diffuse large B cell lymphoma (DLBCL) is rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP). A significant number of patients were not treated with recommended dose of rituximab due to limited financial resources in Malaysia. This study evaluates the efficacy of R-CHOP like chemotherapy in Malaysian patients with DLBCL. Materials and Methods: The study comprised a retrospective analysis of patients with DLBCL treated at a single centre. The outcome was compared with patients who were treated with R-CHOP like and CHOP like chemotherapy. Patients who were treated with lower dose of rituximab was subanalysed for outcome. Results: A total of 86 patients who had CHOP-like chemotherapy were included. Only 39 (45%) patients had rituximab and only 12 (29%) patients had the recommended dose. The overall response (OR) and complete response (CR) rates were 88% and 81% respectively. There was no significant difference in OR and CR in patients who had rituximab and those without rituxmab. Those with International Prognostic Index (IPI) score of ${\leq}2$ had significant higher CR rate, progression free survival (PFS) and overall survival (p<0.001). Conclusions: The lack of significant improvement in CR and DFS in our patients may be due to an inadequate dose of rituximab.


  1. Shiozawa E, Yamochi-Onizuka T, Takimoto M, et al ( 2007). The GCB subtype of diffuse large B-cell lymphoma is less frequent in Asian countries. Leuk Res, 31, 1579-83.
  2. Sehn LH, Donalson J, Chhanabhai M, et al (2005), Introduction of combined CHOP plus rituximab therapy dramatically improved outcome of diffuse large B cell lymphoma in British Columbia. J Clin Oncol, 23, 5027-33.
  3. Seiki R, Ohshima K, Nagafuji K, et al (2010). Rituximab in combination with CHOP chemotherapy for the treatment of diffuse large B cell lymphoma in Japan: a retrospective analysis of 1,057 cases from Kyushu Lymphoma Study Group. Int J Hematol, 91, 258-66.
  4. Shia AKH, Gan GG, Jairaman S, Peh SC, et al (2005). High frequency of germinal centre derivation n diffuse large B cell lymphoma from Asian patients. J Clin Pathol, 58, 962-7.
  5. Teo MC, Soo KC (2013) Cancer trends and incidences in Singapore. Jpn J Clin Oncol, 43, 219-24.
  6. Visco C, Tzankov A, Xu-Manoette ZY, et al (2013). Patients with diffuse large B cell lymphoma of germinal centre with BCL2 translocation have poor outcome; irrespective of MYC status: a report from an international DLBCL rituximab- CHOP consortium program study. Haematologica, 98, 255-63.
  7. Vose JM, Link BK, Grossbard ML, et al (2001). Phase II study of rituximab in combination of CHOP chemotherapy in patients with previously, untreated aggressive non-Hodgkin lymphoma. J Clin Oncol, 19, 387-97.
  8. Ngo L, Hee SW, Lim LC, et al (2008). Prognostic factors in patients with diffuse large B cell lymphoma: before and after introduction of rituximab. Leukemia Lymphoma, 49, 462-9.
  9. Lenz G, Wright DH, Dave SS, et al (2007). Gene expression signatures predict overall survival in diffuse large B cell lymphoma treated with rituximab and CHOP-like chemotherapy. Blood, 110, 109.
  10. Li JM, Wang L, Shen Y, et al (2007). Rituximab in combination with CHOP chemotherapy for the treatment of diffuse large B cell lymphoma in Chinese patients. Ann Hematol, 86, 639-45.
  11. Li Y, Yimamu M, Wang X, et al (2014). Addition of rituximab to a CEOP regimen improved the outcome in the treatment of non-germinal center immunophenotype diffuse large B-cell lymphoma cells with high Bcl-2 expression. Int J Hematol, 99, 79-86.
  12. Nishimori H, Matsua K, Maeda Y, et al (2009). The effect of adding rituximab to CHOP based therapy on clinical outcomes for Japanese patients with diffuse large b cell lymphoma: a propensity score matching analysis. Int J Hematol, 89, 326-31.
  13. Park YH, Lee JJ, Ryu MH, et al (2006). Improved therapeutic outcomes of DLBCL after introduction of rituximab in Korean patients. Int J Haem, 85, 257-2.
  14. Pfreundschuh M, Trumper L, Ostenberg A, et al (2006). CHOP like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good prognosis diffuse large B cell lymphoma: a randomized controlled trial by the MabThera international trial (MInT) group. Lancet Oncol, 7, 379-91.
  15. Rosenwald A, Wright G, Chan WC, et al (2002). The use of molecular profiling to predict survival after chemotherapy for diffuse large B-cell lymphoma. New Eng J Med, 346, 1937-47.
  16. Chihara D, Ito H, Matsuda T, et al (2013). Differences in incidence and trends of hematological malignancies in Japan and United States. Br J Haematol, 164, 536-45.
  17. Armitage JO (2012). My treatment approach to patients with Diffuse Large B cell Lymphoma. Mayo Clin Pro, 87, 161-71.
  18. Blay J, Gomez F, Sebban C, et al (1998). The International Prognostic Index correlates to survival in patients with aggressive lymphoma in relapse: analysis of the PARMA trial. Blood, 92, 3562-8.
  19. Castillo JJ, Sinclair N, Beltran BE, et al (2013). Similar outcomes in Asian and Western patients with diffuse large B cell lymphoma treated witn R-CHOP. Leukemia res, 37, 386-91.
  20. Coiffer B, Lepage E, Briere J, et al (2002). CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large B cell lymphoma. New Eng J Med, 346, 235-42.
  21. Feugier P, Van Hoof A, Sebban C, et al (2005). Long term results of the R-CHOP study in the treatment of elderly patients with diffuse large B cell lymphoma, a study by European Groupe D'Estude des Lymphomes des L'Adulte (GELA). J Clin Oncol, 23, 4117-26.
  22. Fu K, Weisinburger DD, Choi WW, et al (2008). Addition of rituximab to standard chemotherapy improves the survival of germinal centre B-cell like and non germinal centre B-cell like subtypes of diffuse large B cell lymphoma. J Clin Oncol, 26, 4587-94.
  23. Huh J (2012). Epidemiologic overview of malignant lymphoma. Korean J Hematol, 47, 92-104.
  24. Intragumthornchai T, BunwarosateU, Siritanaratkul N, et al (2013). Inferior progression free survival for Thai patients with diffuse largeB-cell lymphoma treated under Universal Coverage Scheme, the impact of rituximab inaccessibility. Leuk Lymp, 54, 83-9.

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