RITUXIMAB EXTENDS PFS IN FOLLICULAR LYMPHOMA

December 29, 2010 — Rituximab (Rituxan; Genentech) maintenance therapy should be considered as first-line treatment in some patients with follicular lymphoma. According to new data published online December 21 in The Lancet, patients treated with rituximab have significantly better progression-free survival and higher response rates than those who did not receive this intervention.

At 2 years, 71.5% of patients in the rituximab group achieved complete or unconfirmed complete response compared with 52.2% in the observation group.

The authors also note that at a median follow-up of 36 months, progression-free survival was 74.9% (95% confidence interval [CI], 70.9 - 78.9) among patients receiving rituximab vs 57.6% (95% CI, 53.2 - 62.0) in the observation group (hazard ratio [HR], 0.55; 95% CI, 0.44 - 0.68; P < .0001).

These results suggest that "rituximab maintenance in patients with high tumor burden follicular lymphoma, who respond to rituximab plus chemotherapy induction, improves progression free survival and should now be considered as first-line treatment for these patients," note lead author Gilles Salles, MD, from the Hospices Civils de Lyon and Université Claude Bernard, Lyon, France, and colleagues.

These results were presented earlier this year at the American Society of Clinical Oncology annual meeting.

How to Interpret Findings

But how should these findings be interpreted? That is the question asked by Jonathan W. Friedberg, MD, in a commentary that accompanies the study.

"The scarcity of a benefit in overall survival after maintenance therapy should be emphasized," says Dr. Friedberg, from the James P. Wilmot Cancer Center, University of Rochester, New York. He also points out that "of considerable interest" is the fact that 2 quality-of-life questionnaires showed no differences between the rituximab group and the observation group.

Although the authors have interpreted this finding as "no decrement in quality of life with maintenance therapy," Dr. Friedberg notes that an alternative and equally plausible explanation is that "there is no benefit in quality of life to the patient in maintaining remission."

"The endpoint of progression-free survival in cancer is used as a surrogate of clinical benefit presuming improved quality of life maintaining remission," he writes. "These findings suggest that this improvement might not be the case in this indolent (and often asymptomatic) disease."

He also notes that longer follow-up of this study is needed to answer many important questions, such as whether rituximab resistance develops in the patients receiving maintenance therapy (which can preclude future therapies) and whether the findings extend to the large group of patients with asymptomatic follicular lymphoma that does not require therapy.

There is also the question of cost. What benefit is necessary to justify the cost? Dr. Friedberg notes that maintenance therapy would cost Medicare more than $60,000 per patient at his institution.

Progression-Free Survival Improved, Overall Survival Similar

In this study, Dr. Salles and colleagues evaluated the potential benefit of 2 years of rituximab maintenance therapy after first-line treatment in 1217 patients with follicular lymphoma.

Of this group, 1019 patients who achieved a complete or partial response were then randomly assigned to receive 2 years of rituximab maintenance therapy (375 mg/m² every 8 weeks; n = 505) or observation (n = 513). The primary endpoint was progression-free survival, and analysis was by intention to treat.

At a median follow-up of 36 months for both groups, 130 patients receiving rituximab and 218 patients in the observation group had documented disease progression. Five patients in the rituximab group and 3 in the observation group died before disease progression.

The authors also note that the risk for progression was significantly decreased among patients who received rituximab maintenance therapy. The median time to progression was not reached in the rituximab maintenance group and was an estimated 48.3 months (95% CI, 38.0 to not reached) in the observation group.

In a multivariate analysis adjusted by prognostic factors, a longer progression-free survival was significantly associated with receiving rituximab maintenance therapy (HR, 0.55; P < .0001), age 60 years or older (HR, 0.68; P = .0013), female sex (HR, 0.76; P = .013), lower Follicular Lymphoma International Prognostic Index score categories (overall P < .0001), and the use of R-CHOP (rituximab plus cyclophosphamide, hydroxydaunorubicin, vincristine [Oncovin], and prednisone) or R-FCM (rituximab plus fludarabine, cyclophosphamide, and mitoxantrone) as induction treatment (HR, 0.39; P = .0029).

However, overall survival did not significantly differ between the 2 groups (HR, 0.87; 95% CI, 0.51 - 1.47).

Rituximab maintenance therapy was generally well tolerated, but grade 3 or 4 adverse events were significantly more common in the rituximab group (24% vs 17%). Grade 2 to 4 infections were the most commonly reported adverse events, occurring in 187 patients (39%) in the rituximab group vs 84 patients (24%) in the observation group (risk ratio, 1.62; 95% CI, 1.35 - 1.96; P < .0001).

This study was funded by Groupe d’Etude des Lymphomes de l’Adulte (GELA; Paris, France) and F Hoffmann-La Roche. Several of the study coauthors have declared potential conflicts of interest, as indicated in the paper.

Lancet. Published online December 21, 2010.