Minimal residual disease after conventional treatment significantly impacts on progression-free survival of patients with follicular lymphoma: The FIL FOLL05 trial

Purpose: The role of the minimal residual disease (MRD) in follicular lymphoma is still debated. In this study, we assessed whether the BCL2/IGH rearrangement could have a prognostic role in patients receiving R-CHOP, R-FM, or R-CVP.

Experimental Design: DNAs from 415 patients among the 504 cases enrolled in the FOLL05 trial (NCT00774826) were centralized and assessed for the BCL2/IGH at diagnosis, at the end of treatment, and after 12 and 24 months.

Conclusions: In this study, standardized molecular techniques have been adopted and applied on bone marrow samples from a large cohort. Data reported show that the MRD detection is a powerful independent predictor of PFS in patients with follicular lymphoma receiving conventional chemoimmunotherapy.

Results: At diagnosis, the molecular marker was detected in 53% of cases. Patients without molecular marker or with a low molecular tumor burden (<1×10⁴ copies) showed higher complete remission (CR) rate and longer progression-free survival (PFS; 3-year PFS 80% vs. 59%; P= 0.015). PFS was significantly conditioned by the PCR status at 12 and 24 months, with 3-year PFS of 66% for MRD^- cases versus 41% for % at 12 months (P = 0.015), and 84% versus 50% at 24 months (P = 0.014). The MRD negativity those MRD⁺ at 12 and 24 months resulted in an improved PFS both in CR and in partial remission (PR) patients (3-year PFS = 72% for cases CR/PCR⁺ vs. 32% for those CR/PCR⁺ vs. 62% for those PR/PCR⁺ and 25% for patients in PR/PCR⁺; P = 0.001). The prognostic value ofMRDat 12 and 24 months of follow-up was confirmed also in multivariate analysis.