Sustained Progression-Free Survival Benefit of Rituximab Maintenance in Patients With Follicular Lymphoma: Long-Term Results of the PRIMA Study

Abstract

PURPOSE The PRIMA study (ClinicalTrials.gov identifier: NCT00140582 ) established that 2 years of rituximab maintenance after first-line immunochemotherapy significantly improved progression-free survival (PFS) in patients with follicular lymphoma compared with observation. Here, we report the final PFS and overall survival (OS) results from the PRIMA study after 9 years of follow-up and provide a final overview of safety. METHODS Patients (> 18 years of age) with previously untreated high–tumor-burden follicular lymphoma were nonrandomly assigned to receive one of three immunochemotherapy induction regimens. Responding patients were randomly assigned (stratified by induction regimen, response to induction treatment, treatment center, and geographic region) 1:1 to receive 2 years of rituximab maintenance (375 mg/m2, once every 8 weeks), starting 8 weeks after the last induction treatment, or observation (no additional treatment). All patients in the extended follow-up provided their written informed consent (data cutoff: December 31, 2016). RESULTS In total, 1,018 patients completed induction treatment and were randomly assigned to rituximab maintenance (n = 505) or observation (n = 513). Consent for the extended follow-up was provided by 607 patients (59.6%) of 1,018 (rituximab maintenance, n = 309; observation, n = 298). After data cutoff, median PFS was 10.5 years in the rituximab maintenance arm compared with 4.1 years in the observation arm (hazard ratio, 0.61; 95% CI, 0.52 to 0.73; P < .001). No OS difference was seen in patients randomly assigned to rituximab maintenance or observation (hazard ratio, 1.04; 95% CI, 0.77 to 1.40; P = .7948); 10-year OS estimates were approximately 80% in both study arms. No new safety signals were observed. CONCLUSION Rituximab maintenance after induction immunochemotherapy provides a significant long-term PFS, but not OS, benefit over observation.

Patterns of change in treatment, response, and outcome in patients with follicular lymphoma over the last four decades: a single-center experience

“…However, taking into account that PET-CT can help consider as a CR a study where there is a residual mass without metabolic activity, the advent of this technique cannot be discarded as a contributing factor to an improvement in observed responses. This deepening of responses translated into a better PFS (40-56% at 5 years, for decades 1 and 4, respectively) and OS (77-86% at 5 years, for decades 1 and 4, respectively), as previously shown by multicenter studies in the rituximab era 23 .…”

Efficacy and infection morbidity of front‐line immuno‐chemotherapy in follicular lymphoma

“…In this study, R‐CVP resulted in lower OS and PFS rates than other induction comparators, which is in part driven by patient selection, but also known to provide an inferior PFS compared to other standard immuno‐chemotherapy regimens 5 . The 3‐year PFS improvement with maintenance mAb is consistent with PRIMA data (79.7% vs. 74.9%) 2 . Our 10‐year OS rate in non‐maintenance patients was significantly lower (40.9%) compared to 80% in the non‐maintenance arm of PRIMA, 2 reflecting the nature of non‐selective consecutive population‐based data in patients with comorbidities.…”

“…Current UK standard of care in front‐line advanced stage (III or IV) symptomatic follicular lymphoma (FL) is immuno‐chemotherapy with anti‐CD20 monoclonal antibodies (mAbs) rituximab (R) or obinutuzumab (O), in combination with cyclophosphamide, vincristine and prednisolone (CVP) or cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP), or bendamustine (B) 1 . Maintenance R or O is commonly offered to patients who achieved an objective response to induction 1,2 …”

How to manage lymphoid malignancies during novel 2019 coronavirus (CoVid-19) outbreak: a Brazilian task force recommendation

“…While maintenance rituximab improves PFS rates, there is an increase in toxicities and there is no OS benefit in a longer follow-up of the PRIMA trial. 28 Moreover, rituximab maintenance has been tested in different schedules, including every 2 or 3 months. Although it is assumed that rituximab infusions every 2 months may maintain better rituximab serum concentration, 29 there is no direct comparison in phase 3 trials.…”