In an analysis from the phase III GALLIUM study reported in the Journal of Clinical Oncology, Pott et al identified measurable residual disease (MRD) status and related outcomes among patients receiving obinutuzumab- and rituximab-based treatment for previously untreated follicular lymphoma.
Study Details
In the trial, patients received induction with obinutuzumab or rituximab plus one of the following:
- Bendamustine
- CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)
- CVP (cyclophosphamide, vincristine, prednisone).
Patients with response received maintenance therapy with obinutuzumab or rituximab according to random assignment.
Key Findings
Among all patients, progression-free survival was poorer among those with detectable MRD at the middle of induction (hazard ratio [HR] = 3.03, 95% confidence interval [CI] = 2.07–4.45, P < .0001) and at the end of induction (HR = 2.25, 95% CI = 1.53–3.32, P < .0001).
Rates of undetectable MRD were higher after obinutuzumab/chemotherapy vs rituximab/chemotherapy at the middle of induction (94.2% vs 88.9%, P = .013) and at the end of induction (93.1% vs 86.7%, P = .0077). Late responders (detectable MRD at the middle of induction, undetectable MRD at the end of induction) had significantly poorer progression-free survival (HR = 3.11, 95% CI = 1.75–5.52, P = .00011) vs early responders (undetectable MRD at both the middle of induction and the end of induction). The smallest proportion of detectable MRD was observed in patients receiving bendamustine at the middle of induction (eg, 4.8% vs 16.0% in those receiving CHOP, P < .0001).
As noted by the investigators, obinutuzumab appeared to compensate for less effective chemotherapy regimens, being associated with similar undetectable MRD rates across the three chemotherapy partners. At the end of induction, undetectable MRD rates were 93.5% vs 91.5% for obinutuzumab/bendamustine vs rituximab/bendamustine, 93.0% vs 79.3% for obinutuzumab/CHOP vs rituximab/CHOP, and 90.6% vs 78.3% for obinutuzumab/CVP vs rituximab/CVP.
During maintenance, more patients treated with rituximab vs obinutuzumab had detectable MRD: for example, 20.7% vs 7.0% of the rituximab/CHOP group vs the obinutuzumab/CHOP group and 21.7% vs 9.4% of the rituximab/CVP group vs the obinutuzumab/CVP group. Throughout maintenance, detectable MRD was associated with clinical relapse.
The investigators concluded: “MRD status can determine outcome after induction and during maintenance, and [undetectable] MRD is a prerequisite for long-term disease control in follicular lymphoma. The higher MRD responses after obinutuzumab- vs rituximab-based treatment confirm more effective tumor cell clearance.”
Christiane Pott, MD, PhD, of the Second Medical Department, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by F. Hoffmann–La Roche Ltd. For full disclosures of the study authors, visit ascopubs.org.
