Rituximab beneficial for maintenance, not purging in FL

Follicular lymphoma cells

CHICAGO—The European Group for Blood and Marrow Transplantation (EBMT)-LYM-1 study showed that purging for stem cell harvest with rituximab was of no benefit, but that rituximab maintenance therapy improved progression-free survival (PFS) in rituximab-naïve patients with follicular lymphoma (FL) undergoing stem cell transplantation. Experts said this study does not address whether these results would be similar in patients with follicular lymphoma treated up front with rituximab.

“Choosing the optimal therapy is challenging for patients with relapsed or resistant follicular lymphoma," said Ruth Pettengell, MD, of St. George’s Hospital in London, at an oral session during ASCO 2010. "Autologous stem cell transplant at first relapse has been shown to prolong remission. Four trials in the rituximab era show about a 20% improvement in PFS and event-free survival [EFS] with rituximab added to high-dose therapy [before transplant], but the effect on overall survival is not established,” she said.

Dr Pettengell reported results of a study of rituximab purging and maintenance rituximab in 280 patients in first remission (n=16), second (n=222), or third (n=42) remission who achieved either a complete response or very good partial remission to induction chemotherapy. Mean age was 51.6 years, and 78.3% were stage III or IV follicular lymphoma. Patients were randomized in a 2 x 2 factorial design to rituximab purging with 375 mg/m² weekly for 4 weeks or no purging, followed by stem cell collection and high-dose chemotherapy, then randomization to rituximab maintenance with 375 mg/m² every 3 months for 2 years or no maintenance.

At baseline, all 4 groups were well balanced for demographic and disease characteristics. About 58% were BCL positive and 25% were BCL unknown; 80% had 2 prior lines of chemotherapy; FLIPI scores were equally divided in all 4 groups. Median time from diagnosis was 44 months. At the time of transplant, 70% had a very good partial remission and 30% had complete remission. There were 87 withdrawals and 53 failures to mobilize stem cells.

One cardiac death was reported in the rituximab purging group and 38 deaths occurred 100 days post-randomization, mostly due to relapse. Patients treated with rituximab had lower hematologic values at 3 months, which did not translate to late neutropenia. Six serious adverse events were reported with maintenance rituximab.

At a median follow-up of 6.4 years, no difference was seen for 5-year PFS between purging or no purging. However, 5-year PFS was 59% with maintenance rituximab versus 42% with observation alone, representing a 35% reduction in progression for those who received rituximab maintenance (P=0.01).

The greatest benefit in 5-year PFS was in the patients treated with both purging and maintenance: 62.9%. Five-year PFS was 56% for maintenance rituximab alone, 46% for purging with rituximab alone, and 42% for observation alone.

“This advantage did not translate to a difference in overall survival,” Dr Pettengell told listeners. Eighty-one percent of both arms (maintenance versus observation) were alive at follow-up.

Maintenance rituximab was safe in this setting, Dr Pettengell said. “Rituximab has high efficacy as first-line treatment in eligible patients. Salvage therapy post autograft and maintenance therapy is successful,” she said.

The investigators were unable to identify a good-risk and poor-risk group in this study.

The study was supported by Roche.