Prognostic Value of Minimal Residual Disease Among Previously Untreated Patients With Follicular Lymphoma

Analysis of the Phase 3 Randomized Multicenter GALLIUM Trial 

Minimal residual disease (MRD) status predicted disease outcomes after induction and during maintenance among previously untreated patients with follicular lymphoma (FL), and additionally, MRD-negative status was noted as a prerequisite for long-term disease control for patients with FL, according to a prospective analysis of the randomized, multicenter, phase 3 GALLIUM trial published in the Journal of Clinical Oncology. 

Christiane Pott, MD, PhD, University Hospital Schleswig-Holstein, Kiel, Germany, and coauthors explain that while “FL still remains incurable,” various trials have shown “increasing evidence that MRD status reflects depth of response and informs prognosis after first-line therapy and relapse in patients with FL.” 

In this analysis, the study authors focused on the results of preplanned MRD assessments among patients enrolled in the GALLIUM trial while they were treated. Potts and colleagues hoped to assess end points regarding the depth and kinetics of MRD response to obinutuzumab chemotherapy or rituximab chemotherapy and the potential prognostic value of MRD status. 

Patients with untreated CD20-positive FL were enrolled in this trial and received obinutuzumab or rituximab, plus bendamustine, cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) chemotherapy, or cyclophosphamide, vincristine, prednisone (CVP) chemotherapy, during induction. Maintenance with the same antibody followed among responders. The study authors assessed MRD status at preplanned time points, including mid-induction, end of induction, and at 4- to 6-month intervals during maintenance and follow-up. 

Results indicated that MRD positivity was correlated with inferior progression-free survival (PFS) at mid-induction (hazard ratio [HR], 3.03 [95% confidence interval [CI], 2.07 to 4.45]) and end of induction (HR, 2.25 [95% CI, 1.53 to 3.32]). MRD response was higher after treatment with obinutuzumab chemotherapy (94.2%) compared to rituximab chemotherapy (88.9%) at mid-induction and end of induction. 

Patients who were late to respond had significantly worse PFS compared to early responders. MRD positivity was observed in the smallest proportion among patients who received bendamustine at mid-induction (4.8%) compared to those who received CHOP (16%). The study authors noted that obinutuzumab compensated for less effective chemotherapy regimens, with comparable MRD response rates across all groups who received obinutuzumab plus chemotherapy. 

A higher number of patients were MRD-positive in groups who received rituximab plus chemotherapy (20.7% of patients who received rituximab plus CHOP and 21.7% of patients who received rituximab plus CVP) compared with groups receiving obinutuzumab plus chemotherapy (7% of patients who received obinutuzumab plus CHOP and 9.4% of patients who received obinutuzumab plus CVP). MRD positivity was associated with clinical relapse. 

Dr Pott and coauthors concluded, “MRD status can determine outcome after induction and during maintenance, and MRD negativity is a prerequisite for long-term disease control in FL.”

“The higher MRD responses after [obinutuzumab-] versus [rituximab]-based treatment confirm more effective tumor cell clearance,” they added. 

Source: 

Pott C, Jurinovic V, Trotman J, et al. Minimal residual disease status predicts outcome in patients with previously untreated follicular lymphoma: a prospective analysis of the phase III GALLIUM study. J Clin Oncol. Published online: December 14, 2023. doi: 10.1200/JCO.23.00838