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

May 1, 2003
Julie M. Vose, MD, MBA

Oncology NEWS International, Oncology NEWS International Vol 12 No 5, Volume 12, Issue 5

This special supplement to Oncology NewsInternational includes updated results ofstudies with anti-CD20 therapy and othertargeted therapies in the treatment oflymphomas, chronic lymphocytic leukemia,and immune thrombocytopenic purpura. Theresults were presented at the American Societyof Hematology 44th Annual Meeting inPhiladelphia, December 6 to 10, 2002.

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.