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R-CHOP Improves Overall and Event-Free Survival in Patients With Aggressive or Poor Prognosis NHL

R-CHOP Improves Overall and Event-Free Survival in Patients With Aggressive or Poor Prognosis NHL

PHILADELPHIA-The addition of rituximab (Rituxan) to the standard cyclophosphamide, doxorubicin, vincristine (Oncovin), and prednisone (CHOP) regimen improves duration of response and eventfree survival in patients with aggressive non-Hodgkin's lymphoma. Although the mechanism of action of rituximab in combination with CHOP (R-CHOP) has not been fully elucidated, it has been hypothesized that rituximab-mediated apoptosis may be enhanced during chemotherapy. Two reports at the American Society of Hematology 2002 Annual Meeting examined the efficacy of RCHOP in patients with aggressive or poor-prognosis lymphoma. Overcoming Resistance Expression of the bcl-2 protein is associated with poor prognosis in patients with diffuse large B-cell lym- phoma (DLBCL) because bcl-2 protein overexpression makes cancer cells resistant to chemotherapy-induced apoptosis. In a study performed by the Groupe d'Etude des Lymphomes de l'Adulte (GELA) in France, investigators have demonstrated the efficacy and safety of R-CHOP in elderly patients with DLBCL.[1] To assess the effect of rituximab on bcl-2-associated disease failure, Nicolas Mounier, MD, PhD, and fellow GELA investigators analyzed bcl-2 expression and clinical outcome from the GELA study (ASH abstract 603).[2] Patients ranged in age from 60 to 80 years, had previously untreated DLBCL, and were randomized to receive standard CHOP or CHOP plus concurrent rituximab (375 mg/m2). The status of bcl-2 protein expression was available for 292 patients with histologically reviewed DLBCL; 193 patients (66%) were bcl-2 positive and 99 patients (34%) were bcl-2 negative. A comparison of baseline patient characteristics and prognostic factors including bcl-2 status indicated that the two groups were similar. The response rates for patients according to bcl-2 status and treatment arm are summarized in Table 1.[2] Response rates, overall survival, and event-free survival were improved with R-CHOP compared with CHOP alone in patients who were bcl-2 positive.[ 2] Furthermore, multivariate analysis confirmed that R-CHOP provided a significant survival benefit in patients who were bcl-2 positive over patients that were bcl-2 negative. These results have since been published.[ 3] The investigators concluded that rituximab overcomes bcl-2-dependent resistance to chemotherapy and recommended further evaluation of R-CHOP in younger patients with DLBCL. R-CHOP Long-Term Follow-up Long-term follow-up data on RCHOP as front-line therapy for patients with aggressive non-Hodgkin's lymphoma was reported by Julie Vose, MD, of the Nebraska University Medical Center in Omaha (ASH abstract 1396).[4] Thirty-three patients were treated. Patient characteristics are summarized in Table 2. In the initial report of this study, the overall response rate was 94% after a median follow-up of 26 months and approximately two thirds of patients achieved a complete response.[ 5] In the more recent report, after a median follow-up of 62 months, 88% of patients are alive and 82% (27 of 33 patients) have not progressed. Figure 1[4] shows time to disease progression or death at 60 months or greater following treatment. Two patients with an International Prognostic Index (IPI) score of 0 or 1 have relapsed and four patients with an IPI score greater than or equal to 2 have relapsed. Four of the relapsing patients died and two were salvaged with chemotherapy and/or stem cell transplantation. No additional long-term complications have been reported during this follow-up period. Therefore, Dr. Vose concluded that R-CHOP is a safe and effective front-line treatment for patients with aggressive non-Hodgkin's lymphoma.

References

1. Coiffier B, Lepage E, Briere J, et al: CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 346:235-242, 2002.
2. Mounier N, Briere J, Gisselbrecht C, et al: Rituximab plus CHOP (R-CHOP) in the treatment of elderly patients with diffuse large B-cell lymphoma (DLBCL) overcomes Bcl2-associated chemotherapy resistance (abstract 603). Blood 100:161a, 2002.
3. Mounier N, Briere J, Gisselbrecht C, et al: Rituximab plus CHOP (R-CHOP) overcomes Bcl-2-associated resistance to chemotherapy in elderly patients with diffuse large Bcell lymphoma (DLBCL). Blood 100 (Feb 6): 2003.
4. Vose JM, Link BK, Grossbard ML, et al: Long term follow-up of a phase II study of rituximab in combination with CHOP chemotherapy in patients with previously untreated aggressive non-Hodgkin’s lymphoma (NHL) (abstract 1396). Blood 100:361a, 2002.
5. Vose JM, Link BK, Grossbard ML, 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 19:389-397, 2001.
 
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