Rituximab (Rituxan) maintenance therapy reduced the risk of recurrence by 50% in patients with follicular lymphoma (FL) who responded to induction therapy with rituximab plus chemotherapy, according to an interim analysis of the Primary Rituximab and Maintenance (PRIMA) phase III study, which compared rituximab maintenance therapy vs observation alone. Maintenance therapy was well tolerated, with little toxicity.

New Standard of Care

"Rituximab maintenance after induction with rituximab plus chemotherapy significantly improved outcomes for FL patients. This study provides evidence for a new standard of care for patients with FL who need treatment," stated Gilles Salles, MD, who is Professor of Medicine at the University of Lyon in Lyon, France. These results were presented at the 2010 ASCO Annual Meeting.¹

FL is the second most common type of lymphoma, and it is usually incurable despite treatment with rituximab plus chemotherapy (chemoimmunotherapy), Dr. Salles explained. FL is typically characterized by recurrence, and the length of remission is shorter with each recurrence. The PRIMA trial was initiated because previous studies suggested that rituximab maintenance might benefit patients with relapsed or previously untreated FL.

The study enrolled 1,217 patients with untreated FL and high tumor burden, primarily stage III or IV, who were age 18 or older and in need of immediate treatment. Patients were initially treated with rituximab plus CHOP (75%), CVP (22%), or FCM (3%).* Responders to initial therapy (n = 1,018) were randomized to observation alone or maintenance rituximab infusions every 2 months for 2 years.

Study Results

At a median follow-up of 25 months, which was the first preplanned interim analysis, the rate of progression-free survival (PFS) was 82% in the rituximab maintenance therapy arm vs 66% of those in the observation arm, which was a highly significant difference (P < .0001).

"This means that the recurrence rate was 18% with rituximab maintenance and 34% with observation alone," Dr. Salles stated.

A consistent benefit was observed for rituximab maintenance therapy for secondary endpoints. The risk of requiring a new round of lymphoma treatment was reduced by 39% (P < .0003 vs observation). Benefits of rituximab maintenance therapy were observed across all subgroups, including age, disease severity, and type of induction chemotherapy received.

"More patients had a complete response or unconfirmed complete response in the group treated with rituximab maintenance therapy," Dr. Salles said.

Rituximab maintenance therapy was well tolerated. Grade 3 and 4 events were more frequent in the maintenance arm (23% vs 16%, respectively) and grade 2 infections were also more frequent (37% vs 22%, respectively). Quality of life was similar in both arms.

"Very few patients withdrew from the trial for toxicity-related reasons-10 in the rituximab arm and 1 in the observation arm," Dr. Salles noted.

Survival Benefit?

This study, conducted by the Groupe d'Etude des Lymphomes de l'Adulte (GELA)-sponsored intergroup, suggests that lymphoma is a chronic disease that is likely to need chronic therapy, said ASCO President George W. Sledge, Jr, MD.

"It is not clear yet whether improved progression-free survival in this trial will translate to improved overall survival, but this study is an important step in this direction," Dr. Sledge stated.

Andrew Zelenetz, MD, PhD, commented, "This is an important and potentially practice-changing study. However, longer follow-up is needed to determine if there is survival benefit, because there is risk for long-term toxicity." Dr. Zelenetz is Chief of the Lymphoma Service at Memorial Sloan-Kettering Cancer Center in New York.

He pointed out that in a retrospective study, he and his colleagues found that about 39% of patients treated with rituximab developed hypogammaglobulinemia and 10% of patients required treatment with IV immune globulin for recurrent infections. During the maintenance period, no significant differences in the median levels of three classes of immunoglobulin were observed between patients on observation and those receiving rituximab maintenance. ■

Reference

1. Salles GA, Seymour JF, Feugier P, et al: Rituximab maintenance for 2 years in patients with untreated high tumor burden follicular lymphoma after response to immunochemotherapy. 2010 ASCO Annual Meeting. Abstract 8004. Presented June 5, 2010.

*CHOP = cyclophosphamide, doxorubicin, vincristine, prednisone; CVP = cyclophosphamide, vincristine, prednisone; FCM = fludarabine, cyclophosphamide, mitoxantrone.