Minimal Residual Disease Predicts Outcome in Follicular Lymphoma

Achievement of minimal residual disease (MRD) negativity in peripheral blood and bone marrow correlates with improved outcomes in patients with B-cell non-Hodgkin lymphoma. These investigators evaluated the prognostic value of MRD status in patients with advanced follicular lymphoma undergoing immunochemotherapy in the industry-sponsored, multicenter, phase 3 GALLIUM trial (NEJM JW Oncol Hematol Oct 12 2017 and N Engl J Med 2017; 377:1331).

Previously untreated patients were randomized to induction with rituximab or obinutuzumab plus chemotherapy, followed by maintenance with the assigned antibody for 2 years. MRD was assessed by nested and quantitative PCR for clonal immunoglobulin gene rearrangement and the t(14;18) breakpoint; positive MRD was indicated if both assays were detectable at or above 10⁴ sensitivity. Samples were collected from blood, bone marrow, or both during and at the end of induction and maintenance therapy.

Of 1064 enrolled patients, 249 (23.4%) had no clonal PCR marker detected or had samples that did not meet MRD evaluability metrics. At a median follow-up of 59 months, MRD positivity at the middle or end of induction was significantly associated with poorer progression-free survival (PFS) and overall survival (OS) and a higher rate of disease progression within 24 months compared with MRD negativity. Three-year PFS was 81.1% for patients who were positron emission tomography (PET)-negative/MRD-negative at the end of induction, versus 58.8% of those PET-negative/MRD-positive and 73.9% of those PET-positive/MRD-negative. Persistent or recurrent MRD-positivity during maintenance therapy correlated strongly with clinical relapse and poorer outcome. MRD-negativity rates were higher in patients treated with bendamustine versus other chemotherapies and in those treated with obinutuzumab versus rituximab.