Results of a clinical trial suggested that for patients with follicular lymphoma (FL), postinduction therapy using a response-adapted approach was associated with a poorer progression-free survival (PFS) than seen with standard postinduction therapy. Results were reported in the Journal of Clinical Oncology.
In the phase 3, noninferiority-based FOLL12 trial (ClinicalTrials.gov Identifier: NCT02063685), the primary endpoint was PFS. Patients who had been previously untreated for FL received induction treatment and then underwent response assessments. These assessments involved computed tomography, 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET), and, for some patients, a polymerase chain reaction (PCR) analysis of peripheral blood and bone marrow specimens. FDG-PET and PCR were used to evaluate minimal residual disease (MRD). Following assessments, patients were randomized to receive either standard rituximab maintenance of 12 doses of 375 mg/m2 (the reference arm) or the experimental postinduction protocol based on molecular response.
In the experimental arm, patients who were in complete metabolic response (CMR) and with MRD-negativity underwent observation. Patients in CMR who had MRD-positivity or became MRD positive during follow-up were given rituximab until reaching MRD negativity or receiving up to 3 courses. Patients who did not achieve CMR at the end-of-induction assessments underwent intensification involving radioimmunotherapy.
A total of 368 patients in the standard rituximab maintenance arm and 376 patients in the experimental arm completed induction and response assessments. The median study follow-up was 53 months (range, 1-92).
The 3-year PFS rate for the standard rituximab maintenance arm was 86% (95% CI, 82%-89%), compared with 72% (95% CI, 67%-76%) for the experimental arm. The experimental, response-adapted arm showed a significantly greater risk of progression (hazard ratio, 1.92; 95% CI, 1.43-2.56) than the reference arm did. The 3-year overall survival rates were similar between treatment arms, at 98% (95% CI, 96%-99%) for the reference arm and 97% (95% CI, 95%-99%) for the experimental arm (P =.238).
For patients who had achieved CMR at end of induction, the 3-year PFS rates were 90% (95% CI, 86%-93%) in the reference arm and 72% (95% CI, 67%-77%) for the experimental arm (P <.001). Among patients who were considered MRD positive, the experimental arm showed inferior 3-year PFS compared with the reference arm (P <.001). For patients who did not achieve CMR, the reference and experimental arms showed similar 3-year PFS rates (P =.274).
In the postinduction phase, among patients reaching CMR with induction, neutropenia of grade 3 to 4 appeared in more patients from the reference arm than the experimental arm. However, in patients without CMR at this assessment, grade 3 or 4 neutropenia and thrombocytopenia occurred at higher rates in the experimental arm.
“The study demonstrated that our response-adapted postinduction therapy resulted in significant inferiority compared with standard maintenance in terms of 3-year PFS (86% v 72%), with a hazard ratio of 1.92,” the study investigators wrote in their report.
Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Luminari S, Manni M, Galimberti S, et al; on behalf of Fondazione Italian Linfomi. Response-adapted postinduction strategy in patients with advanced-stage follicular lymphoma: the FOLL12 Study. J Clin Oncol. Published online October 28, 2021. doi:10.1200/JCO.21.01234