New Orleans, LA—Findings from 2 major studies presented at ASH 2013 indicate that the longer the maintenance period, the greater the duration of progression-free survival (PFS) in follicular lymphoma (FL); however, overall survival (OS) was still not improved, even at 6 years of follow-up.
Andrew Zelenetz, MD, former Chief of Lymphoma Service at Memorial Sloan-Kettering Cancer Center, New York, commented that lacking an OS benefit, he does not believe maintenance is “standard of care” or mandatory. He discusses the data with his patients, and said that approximately 70% of them choose observation (ie, waiting to retreat on progression).
“If there is a compelling reason for the patient to delay the time to next treatment, then it makes sense, but that is an individual case-by-case discussion between the doctor and patient,” he suggested.
Two Randomized Trials
In the randomized phase 3 SAKK 35/03 trial, median PFS doubled when treatment with rituximab was continued to a maximum of 5 years, and this benefit of prolonged maintenance occurred “without increased undue toxicity,” said Christian J. Taverna, MD, of Kantonsspital in Munsterlingen, Switzerland.
This trial was initiated in 2004 to determine if maintenance with rituximab every 2 months for 5 years or until relapse or progression, unacceptable toxicity or death, would be superior to maintenance every 2 months for 4 treatments. A total of 270 patients with untreated, relapsed, stable, or chemotherapy-resistant FL (all grades) were included; all received 4 weekly doses of rituximab.
The 165 patients reaching a complete or partial response to this induction regimen were randomly assigned to rituximab as short-term maintenance (4 administrations every 2 months) or to long-term maintenance (every 2 months for a maximum of 5 years). The primary end point was event-free survival. The events included disease progression or relapse, unacceptable toxicity, death from any cause, the initiation of nonprotocol or concomitant steroids or radiotherapy, or secondary malignancy.
The event-free survival end point was not met with long-term maintenance rituximab, but Dr Taverna attributed this to the unusual imbalance in events before the patients received different therapies. Specifically, more patients in the short-term maintenance arm (3 vs 10) progressed or relapsed during the first 8 months after randomization, when treatments in both arms were the same.
In an analysis of only patients at risk after 8 months from randomization, however, median event-free survival was significantly prolonged with longer maintenance—7.1 years compared with 2.9 years (P = .004). Furthermore, the secondary end point of PFS was significantly improved with longer maintenance, from 3.5 years in the short-term arm to 7.4 years in the long-term arm (P = .04), but OS and response rates were similar.
Gilles Andre Salles, MD, PhD, of the Université Claude Bernard in Lyon, France, presented updated 6-year follow-up of the PRIMA study of 2-year rituximab maintenance, showing a 43% reduction in disease progression and a 38% reduction in time to next treatment, but no improvement in OS.
PRIMA enrolled 1217 patients treated with various rituximab-based induction, then randomized 1018 patients to observation or to rituximab maintenance. At 3 years, in the initial analysis, PFS rates were 75% for maintenance versus 58% for observation (P &li;.001). In the updated analysis, with a median follow-up of 6 years, the PFS was 59.2% and 42.7%, respectively (P &li;.001). At 70 months, subsequent treatment was required by 63.5% versus 51.0%, respectively (P &li;.001).
The OS rates were “excellent,” Dr Salles said, at 88.7% and 87.4%, respectively, but were not superior with maintenance.
“Rituximab maintenance did not lead to the selection of more aggressive clones in these patients,” Dr Salles said. Approximately 50% of all deaths were associated with FL progression in each arm.