Long-term follow-up of patients with follicular lymphoma using next generation sequencing to detect minimal residual disease

Background Follicular lymphoma (FL) is a highly treatable, indolent non-Hodgkin lymphoma. Although FL is considered incurable, a patient without progression of disease by 24 months after treatment is predicted to have a survival consistent with persons without lymphoma. Using a sensitive assessment of minimal residual disease (MRD), we tested the hypothesis that MRD monitoring can predict long term remissions. Methods Unselected patients who were in a clinical remission for at least 24 months after their last treatment were enrolled and monitored prospectively for MRD detectability using a sensitive next-generation sequencing assay (clonoSEQ, Adaptive Biotechnologies, Seattle, WA). Results Forty-seven consecutive patients were monitored. We evaluated the MRD thresholds 10−4, 10−5, and 10−6 for the ability to predict long-term remissions in this cohort and determined that undetectable disease at 10−6 was the best predictor with a specificity and negative predictive value (NPV) of 70% and 100%, respectively. While 3 patients exhibited clinical disease progression during the course of the study, none of the 31 patients with persistent MRD undetectability at 10−6 experienced relapse. Conclusions A significant proportion (31/47; 66.0%) of FL patients in clinical remission after ≥ 24 months following last therapy were undetectable at 10−6 by a sensitive assay of MRD. The threshold of sensitivity was 100%, specificity 70%, with a PPV of 19%, but a NPV of 100%. Although longer follow-up is needed for confirmation, many of these patients may continue to have durable complete remissions. MicroAbstract This study describes the utility of next-generation sequencing (NGS) using the ClonoSEQ platform to assess minimal residual disease (MRD) in unselected patients with follicular lymphoma (FL) who were in remission for 24 months or longer after their last treatment. In a cohort of 47 evaluable patients, we demonstrate a 100% negative predictive value for relapse for a MRD threshold of 10−6. Of the 31 patients in our study who had undetectable FL cells among 10−6 tested, none experienced a relapse. Although longer follow-up is needed for confirmation, many of these patients may continue to have durable complete remissions highlighting the potential curability of FL.