Standard induction and maintenance therapy
MabThera maintenance therapy is approved for patients with relapsed/refractory FL responding to induction therapy with chemotherapy with or without MabThera. This approval was based on the results of the EORTC 20981 trial, a large randomised trial to evaluate the effect of MabThera plus cyclophosphamide, vincristine, prednisone and doxorubicin (CHOP) chemotherapy on the quality and duration of response in relapsed or refractory FL patients, and the effect of subsequent MabThera maintenance therapy on progression-free survival (PFS).1 Eligible patients who had responded to CHOP or MabThera plus CHOP induction therapy (n=334) were randomised to receive either MabThera maintenance therapy (one infusion at 3-monthly intervals for 2 years) or observation.
MabThera maintenance therapy prolongs response to induction chemotherapy |
Following the second randomisation, median PFS was extended by ~3 years by addition of MabThera maintenance. OS was also found to be significantly increased for patients receiving MabThera maintenance therapy compared with observation after a median follow-up of 33.3 months from the second randomisation (median PFS: 51.5 vs 14.9 months, p<0.001; and 3-year OS: 85.1% vs 77.1%, p=0.011).1
Long-term follow up confirmed that the benefits of MabThera are maintained with time.2 At a median follow up of 6 years (from the start of MabThera maintenance therapy) PFS was again found to be prolonged by MabThera compared with observation alone (median PFS from second randomisation 44 months versus 16 months, respectively; hazard ratio [HR]: 0.55; p<0.0001). These findings suggest that MabThera maintenance therapy can help patients with FL regain a more normal pattern of life by offering years of additional time between relapses.2
Importantly, the PFS benefit was seen in patients who received CHOP induction (HR: 0.37; p<0.0001) and those who received MabThera-CHOP induction (HR: 0.69; p=0.043) showing that all relapsed FL patients can benefit from MabThera maintenance therapy regardless of their induction regimen. The survival rate at 5 years was 74% with MabThera maintenance therapy and 64% with observation alone (p=0.07) but as MabThera is standard of care for relapsed FL most of these patients (59%) had received MabThera-based salvage therapy, and this probably influenced survival in the observation arm of the study.2
All relapsed FL patients can benefit from MabThera maintenance therapy regardless of their induction regimen |
Notably, a meta-analysis of five trials including 985 patients confirmed that MabThera maintenance treatment affords a significant OS benefit compared with observation or retreatment at relapse (hazard ratio for mortality = 0.60, 95% confidence interval: 0.45–0.79; p = 0.0003).3
A cost-effective analysis has been undertaken using the data from EORTC 20981 to estimate the cost/benefit ratio of MabThera maintenance therapy in relapsed/refractory FL versus observation alone.4 This analysis included those patients who had responded to induction therapy (with or without MabThera), with a median follow-up of 28 months. MabThera maintenance therapy resulted in an additional 0.8 quality-adjusted life years (QALY). The incremental cost-effectiveness ratio for MabThera maintenance therapy was $20,428 (Canadian) per QALY. The cost-effectiveness of MabThera did not change significantly when the effectiveness and cost variables were adjusted in sensitivity analyses.
MabThera maintenance therapy after combination chemotherapy therapy is cost effective in relapsed/refractory follicular lymphoma |
