Abstract
We conducted a retrospective analysis to evaluate the impact on clinical outcomes of adding rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) treatment for diffuse large B-cell lymphoma (DLBCL) patients in Japan. A propensity score method was used to compensate for the non-randomized study design. From January 2000 to December 2004, 378 patients who were newly diagnosed with DLBCL at 13 institutes were enrolled: 123 in the rituximab plus CHOP-based chemotherapy (R+) group, and 255 in the CHOP-based chemotherapy only (R−) group. The complete response rate was significantly higher in the R+ group than in the R− group (77.7 vs. 69.4%, P < 0.001). The progression-free survival (PFS) at 2 years was 62.4% in the R+ group and 57.0% in the R− group. The 2-year overall survival (OS) was 76.9% for the R+ group and 70.5% for the R− group. A multivariate analysis revealed that the addition of rituximab was a strong independent prognostic factor for PFS (hazard ratio 0.64, 95% CI 0.43–0.96, P = 0.031). A subgroup analysis revealed that R+ particularly benefited younger patients (hazard ratio 0.25, 95% CI 0.08–0.75, P = 0.013). IPI also showed significant impact for PFS (hazard ratio 1.82, 95% CI 1.55–2.14 for one score increase, P < 0.001) as well as OS (hazard ratio 2.10, 95% CI 1.71–2.57, P < 0.001). In summary, the addition of rituximab to CHOP-based chemotherapy results in better outcomes for Japanese DLBCL patients, particularly younger patients.
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References
A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin’s lymphoma. The Non-Hodgkin’s Lymphoma Classification Project. Blood. 1997;89:3909–18.
McKelvey EM, Gottlieb JA, Wilson HE, Haut A, Talley RW, Stephens R, et al. Hydroxyldaunomycin (Adriamycin) combination chemotherapy in malignant lymphoma. Cancer. 1976;38:1484–93. doi:10.1002/1097-0142(197610)38:4<1484::AID-CNCR2820380407>3.0.CO;2-I.
Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, et al. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin’s lymphoma. N Engl J Med. 1993;328:1002–6. doi:10.1056/NEJM199304083281404.
Gordon LI, Harrington D, Andersen J, Colgan J, Glick J, Neiman R, et al. Comparison of a second-generation combination chemotherapeutic regimen (m-BACOD) with a standard regimen (CHOP) for advanced diffuse non-Hodgkin’s lymphoma. N Engl J Med. 1992;327:1342–9.
Reff ME, Carner K, Chambers KS, Chinn PC, Leonard JE, Raab R, et al. Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood. 1994;83:435–45.
Tobinai K, Igarashi T, Itoh K, Kobayashi Y, Taniwaki M, Ogura M, et al. Japanese multicenter phase II and pharmacokinetic study of rituximab in relapsed or refractory patients with aggressive B-cell lymphoma. Ann Oncol. 2004;15:821–30. doi:10.1093/annonc/mdh176.
McLaughlin P, Grillo-Lopez AJ, Link BK, Levy R, Czuczman MS, Williams ME, 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;16:2825–33.
Vose JM, Link BK, Grossbard ML, Czuczman M, Grillo-Lopez A, Gilman P, et al. Phase II study of rituximab in combination with chop chemotherapy in patients with previously untreated, aggressive non-Hodgkin’s lymphoma. J Clin Oncol. 2001;19:389–97.
Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002;346:235–42. doi:10.1056/NEJMoa011795.
Pfreundschuh M, Trumper L, Osterborg A, Pettengell R, Trneny M, Imrie K, et al. 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. Lancet Oncol. 2006;7:379–91. doi:10.1016/S1470-2045(06)70664-7.
Feugier P, Van Hoof A, Sebban C, Solal-Celigny P, Bouabdallah R, Ferme C, et al. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d’Etude des Lymphomes de l’Adulte. J Clin Oncol. 2005;23:4117–26. doi:10.1200/JCO.2005.09.131.
Matsuyama F, Fukuhara S, Oguma S, Amakawa R, Tanabe S, Kato I, et al. Geographical aspects of bcl-2 gene involvement in Japanese patients with non-Hodgkin’s B-cell lymphomas. Int J Hematol. 1992;55:71–9.
Yasukawa M, Bando S, Dolken G, Sada E, Yakushijin Y, Fujita S, et al. Low frequency of BCL-2/J(H) translocation in peripheral blood lymphocytes of healthy Japanese individuals. Blood. 2001;98:486–8. doi:10.1182/blood.V98.2.486.
Hirose Y, Masaki Y, Karasawa H, Shimoyama K, Fukushima T, Kawabata H, et al. Incidence of diffuse large B-cell lymphoma of germinal center B-cell origin in whole diffuse large B-cell lymphoma: tissue fluorescence in situ hybridization using t(14;18) compared with immunohistochemistry. Int J Hematol. 2005;81:48–57. doi:10.1532/IJH97.04102.
Paik JH, Jeon YK, Park SS, Kim YA, Kim JE, Huh J, et al. Expression and prognostic implications of cell cycle regulatory molecules, p16, p21, p27, p14 and p53 in germinal centre and non-germinal centre B-like diffuse large B-cell lymphomas. Histopathology. 2005;47:281–91. doi:10.1111/j.1365-2559.2005.02222.x.
Rojnuckarin P, Assanasen T, Chotipuech A, Ruangvejvorachai P, Tansatit M, Wannakrairot P, et al. High frequency of BCL2 translocation in Thai patients with follicular lymphomas. Int J Hematol. 2007;86:352–7. doi:10.1532/IJH97.A20709.
A predictive model for aggressive non-Hodgkin’s lymphoma. The International Non-Hodgkin’s Lymphoma Prognostic Factors Project. N Engl J Med. 1993;329:987–94. doi:10.1056/NEJM199309303291402.
Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, 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;17:1244.
Rosenbaum PR, Rubin DB. The central role of the propensity score in observational studies for causal effects. Biometrika. 1983;70:41–55. doi:10.1093/biomet/70.1.41.
Joffe MM, Rosenbaum PR. Invited commentary: propensity scores. Am J Epidemiol. 1999;150:327–33.
Becker SO, Ichino A. Estimation of average treatment effects based on propensity score. Stata J. 2002;2:358–77.
Kaplan E, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457–81. doi:10.2307/2281868.
Mantel N. Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep. 1966;50:163–70.
Sehn LH, Donaldson J, Chhanabhai M, Fitzgerald C, Gill K, Klasa R, et al. Introduction of combined CHOP plus rituximab therapy dramatically improved outcome of diffuse large B-cell lymphoma in British Columbia. J Clin Oncol. 2005;23:5027–33. doi:10.1200/JCO.2005.09.137.
Park YH, Lee JJ, Ryu MH, Kim SY, Kim DH, Do YR, et al. Improved therapeutic outcomes of DLBCL after introduction of rituximab in Korean patients. Ann Hematol. 2006;85:257–62. doi:10.1007/s00277-005-0050-8.
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Nishimori, H., Matsuo, K., Maeda, Y. et al. 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, 326–331 (2009). https://doi.org/10.1007/s12185-009-0259-8
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DOI: https://doi.org/10.1007/s12185-009-0259-8