Exploring the Value
of Rituximab in
Non-Hodgkin Lymphoma

S. Vincent Rajkumar, M.D.,

At a time when R-CHOP has quickly become standard induction therapy for diffuse large cell lymphoma, results of a Phase III Intergroup Study presented at the meeting have stirred controversy and discussion. During yesterday’s Plenary Session, Dr. Thomas Habermann presented the findings of this study comparing rituximab/CHOP (R-CHOP) versus CHOP alone, with a second randomization to maintenance rituximab or observation in patients 60 years of age or older with diffuse large cell lymphoma. Six hundred thirty two patients were randomized to R-CHOP (318 patients) or CHOP (314 patients). After completion of the initial treatment, patients were then randomized to maintenance therapy with rituximab weekly x 4 every 6 months (207 patients) versus observation (208 patients).

There was no statistically significant difference in response rate, time to treatment failure, or overall survival between R-CHOP and CHOP given as initial therapy. However, an unplanned weighted analysis performed to remove the confounding effect of maintenance therapy demonstrated improvement in time to failure and overall survival with R-CHOP. On the question of maintenance, the study demonstrated a benefit with rituximab in time to treatment failure only among patients who did not receive the drug during induction therapy, but no significant difference in overall survival was seen.

The results of this study are quite different from an earlier study published last year by Dr.Bertrand Coiffier and colleagues. In that study, event-free and overall survival were significantly better with R-CHOP compared to CHOP alone, with two-year survival rates of 70% versus 57% respectively. Dr. Thomas Habermann, the principal investigator of the Intergroup Study, notes that while the study he led supports the role of rituximab in the treatment of diffuse large cell lymphoma, “more research is needed to determine which patients best benefit from this therapy, and the timing of rituximab administration during induction therapy.”

Interestingly, at yesterday’s Simultaneous Session on Chemotherapy/Rituximab Combinations and Radioimmunotherapy, results from a non-randomized study presented by Dr. Laurie Sehn showed significant improvement in outcome with R-CHOP compared to CHOP alone in diffuse large cell lymphoma. This study compared outcomes in British Columbia, Canada, between patients with large cell lymphoma treated before and after a policy change to use routine R-CHOP for the initial treatment of this disease.

Several other abstracts are being presented at the meeting looking at the role of rituximab in the treatment of Non-Hodgkin lymphoma. At a Simultaneous Session today on Non-Hodgkin Lymphoma: Treatment I (11:00 a.m. - 12:30 p.m.), results of a prospective German Lymphoma Study Group (GLSG) will be presented. In this trial, previously untreated patients with follicular lymphoma were randomized to receive six courses of CHOP or R-CHOP. Time to treatment failure was significantly better with R-CHOP. At the same session the GLSG also presents the results of a randomized trial comparing FCM (fludarabine, cyclophosphamide, mitoxantrone) to FCM plus rituximab (R-FCM) in recurrent follicular or mantle cell lymphoma. Results of trials combining rituximab with other active agents including epratuzumab (anti CD22) and thalidomide analogs (CC-5013, CC-4047) will be presented at today’s Simultaneous Session on Rituximab and Biological Combinations (7:30 a.m. – 9:00 a.m.).