Minimal residual disease in non-Hodgkin lymphoma - current applications and future directions

Non-Hodgkin Lymphomas (NHLs) are a heterogeneous group of tumours with distinct treatment paradigms, but in all cases the goal of treatment is to maximize quality and duration of remission while minimizing therapy-related toxicity. Identification of persistent disease or relapse is most often the trigger to intensify or re-initiate anti-neoplastic therapy, respectively. In the current era of NHL treatment, this determination is mostly based on imaging and clinical evaluations, tools with imperfect sensitivity and specificity. The availability of minimal residual disease (MRD) monitoring could transform treatment paradigms by allowing intensification of treatment in at-risk patients or early intervention for impending relapse. Novel methods based on polymerase chain reaction and next-generation sequencing are now being studied in NHL with promising results. This review outlines the current status of the field in the use of MRD techniques for diffuse large B-cell lymphoma, mantle cell lymphoma and follicular lymphoma. Specifically, we address their demonstrated and potential clinical utility in risk stratification, monitoring of remission status, and guiding interim and post-treatment escalation. Future applications of these techniques could identify novel markers of MRD, improve initial treatment selection, guide treatment escalation or de-escalation, and allow for real-time monitoring of patterns of clonal evolution, which together could redefine NHL treatment paradigms.