Metabolic and molecular response-adapted therapy was associated with significantly worse progression-free survival (PFS) compared with two years of rituximab maintenance in patients with follicular lymphoma (FL), according to results of the FOLL12 study that were published in the Journal of Clinical Oncology.
Rituximab is currently recommended as two-year maintenance treatment in patients with FL who respond to induction immunochemotherapy. This maintenance treatment has been shown to reduce the risk of disease progression, but no effect on overall survival (OS) has been shown.
To better define the quality of a patient’s response and the need for maintenance therapy, the FOLL12 trial was designed to test the noninferiority of a response-adapted postinduction strategy for selection for maintenance rituximab.
“The FOLL12 study was the first one to assess a response-adapted management for patients with FL,” said lead author Stefano Luminari, MD, of University of Modena and Reggio Emilia in Italy.
In the study, patients with treatment-naive, advanced stage disease with high-tumor burden were randomly assigned to standard rituximab maintenance (n=393) or a response-adapted postinduction approach (n=393). The response-adapted approach was based on metabolic response and molecular assessment of measurable residual disease (MRD).
In the response-adapted arm, patients who had complete metabolic response (CMR) and were MRD-negative were assigned to observation; patients with CMR who were MRD-positive received four doses of rituximab and then tested again for MRD. Patients who were still positive for MRD received weekly rituximab until they were MRD-negative up to three doses; and patients without CMR received one dose of ibritumomab tiuxetan followed by standard rituximab maintenance.
“The study results were able to confirm that both molecular and metabolic response were prognostic for the risk of disease progression after induction immunochemotherapy, but also that a complete metabolic and molecular response cannot be used to decide to avoid rituximab maintenance without increasing the risk of disease progression,” Dr. Luminari said.
With a median follow-up of 53 months, patients assigned to rituximab maintenance had significantly better PFS than those in the response-adapted arms. The three-year PFS rate was 86% with rituximab maintenance compared with 72% without (p<0.001).
This better PFS seen with rituximab maintenance was confirmed when looking at all subgroups of treatment, except for patients without CMR.
There was no difference in OS between the study arms. The three-year OS was 98% with rituximab maintenance and 97% with the response-adapted approach.
“In addition to the main results, the FOLL12 trial confirmed the excellent outcome of patients with advanced stage symptomatic FL and the very high response rates achieved with induction immunochemotherapy,” Dr. Luminari said.
Of the 786 patients randomly assigned, 744 completed induction therapy. Of these, 712 achieved a response, making the overall response rate 96%.
“Ten years after the PRIMA trial, our study was able to provide indirect prospective evidence about the efficacy of rituximab maintenance that should be considered the standard choice to grant patients the best efficacy of treatment,” Dr. Luminari said.
In the discussion of these results, Dr. Luminari and colleagues noted that treatment adaption is a “relevant clinical question to optimize treatment exposure, safety, and costs, but caution should be used, as putative benefit may not compensate for an acceptable loss of efficacy, as shown in the present study.”
Based on these results, Dr. Luminari said that molecular response to induction immunochemotherapy as assessed in the study, was not confirmed as an actionable predictive biomarker for patients with FL.
“Additional analyses are underway to assess if different MRD techniques, different timepoints as well as MRD kinetics, could help to better characterize the role of MRD as a biomarker in FL,” he added.
Any conflicts of interest declared by the authors can be found in the original article.
Reference
Luminari S, Manni M, Salimberti S, et al. Response-adapted postinduction strategy in patients with advanced-stage follicular lymphoma: The FOLL12 study [published online ahead of print, 2021 Oct 28]. J Clin Oncol. doi: 10.1200/JCO.21.01234.
