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

PHILADELPHIA-The additionof rituximab (Rituxan) to thestandard cyclophosphamide, doxorubicin,vincristine (Oncovin), andprednisone (CHOP) regimen improvesduration of response and eventfreesurvival in patients with aggressivenon-Hodgkin's lymphoma.Although the mechanism of action ofrituximab in combination withCHOP (R-CHOP) has not been fullyelucidated, it has been hypothesizedthat rituximab-mediated apoptosismay be enhanced during chemotherapy.Two reports at the AmericanSociety of Hematology 2002 AnnualMeeting examined the efficacy of RCHOPin patients with aggressive orpoor-prognosis lymphoma.Overcoming ResistanceExpression of the bcl-2 protein isassociated with poor prognosis in patientswith diffuse large B-cell lym-phoma (DLBCL) because bcl-2 proteinoverexpression makes cancer cellsresistant to chemotherapy-inducedapoptosis. In a study performed bythe Groupe d'Etude des Lymphomesde l'Adulte (GELA) in France, investigatorshave demonstrated the efficacyand safety of R-CHOP in elderlypatients with DLBCL.[1] To assessthe effect of rituximab on bcl-2-associateddisease failure, Nicolas Mounier,MD, PhD, and fellow GELA investigatorsanalyzed bcl-2 expression andclinical outcome from the GELA study(ASH abstract 603).[2]Patients ranged in age from 60 to80 years, had previously untreatedDLBCL, and were randomized to receivestandard CHOP or CHOP plusconcurrent rituximab (375 mg/m²).The status of bcl-2 protein expressionwas available for 292 patients withhistologically reviewed DLBCL; 193patients (66%) were bcl-2 positiveand 99 patients (34%) were bcl-2 negative.A comparison of baseline patientcharacteristics and prognosticfactors including bcl-2 status indicatedthat the two groups were similar.The response rates for patients accordingto bcl-2 status and treatmentarm are summarized in Table 1.[2]Response rates, overall survival, andevent-free survival were improvedwith R-CHOP compared with CHOPalone in patients who were bcl-2 positive.[2] Furthermore, multivariateanalysis confirmed that R-CHOP provideda significant survival benefit inpatients who were bcl-2 positive overpatients that were bcl-2 negative.These results have since been published.[3]The investigators concluded thatrituximab overcomes bcl-2-dependentresistance to chemotherapy andrecommended further evaluation ofR-CHOP in younger patients withDLBCL.

R-CHOP Long-TermFollow-upLong-term follow-up data on RCHOPas front-line therapy for patientswith aggressive non-Hodgkin'slymphoma was reported by Julie Vose,MD, of the Nebraska University MedicalCenter in Omaha (ASH abstract1396).[4]

Thirty-three patients were treated.Patient characteristics are summarizedin Table 2. In the initial report of thisstudy, the overall response rate was94% after a median follow-up of 26months and approximately two thirdsof 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% (27of 33 patients) have not progressed.Figure 1[4] shows time to disease progressionor death at 60 months orgreater following treatment.

Two patients with an InternationalPrognostic Index (IPI) score of 0 or 1have relapsed and four patients withan IPI score greater than or equal to 2have relapsed. Four of the relapsingpatients died and two were salvagedwith chemotherapy and/or stem celltransplantation.No additional long-term complicationshave been reported during thisfollow-up period. Therefore, Dr. Voseconcluded that R-CHOP is a safe andeffective front-line treatment for patientswith aggressive non-Hodgkin'slymphoma.

References:

1.

Coiffier B, Lepage E, Briere J,et al: CHOP chemotherapy plusrituximab compared with CHOPalone in elderly patients with diffuselarge-B-cell lymphoma. N Engl J Med346:235-242, 2002.

2.

Mounier N, Briere J, GisselbrechtC, et al: Rituximab plus CHOP(R-CHOP) in the treatment of elderlypatients with diffuse large B-cell lymphoma(DLBCL) overcomes Bcl2-associatedchemotherapy resistance (abstract603). Blood 100:161a, 2002.

3.

Mounier N, Briere J, GisselbrechtC, et al: Rituximab plus CHOP(R-CHOP) overcomes Bcl-2-associatedresistance to chemotherapy inelderly patients with diffuse large Bcelllymphoma (DLBCL). Blood 100(Feb 6): 2003.

4.

Vose JM, Link BK, GrossbardML, et al: Long term follow-up of aphase II study of rituximab in combinationwith CHOP chemotherapy inpatients with previously untreatedaggressive non-Hodgkin’s lymphoma(NHL) (abstract 1396). Blood100:361a, 2002.

5.

Vose JM, Link BK, GrossbardML, et al: Phase II study of rituximabin combination with CHOP chemotherapyin patients with previouslyuntreated, aggressive non-Hodgkin’slymphoma. J Clin Oncol 19:389-397,2001.