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GALLIUM: MRD response correlates with outcomes in follicular lymphoma



– Minimal residual disease (MRD) response at the end of induction correlates with outcomes in previously untreated follicular lymphoma patients who receive obinutuzumab- or rituximab-based immunochemotherapy, according to updated results from the phase 3 GALLIUM study.

After 57 months of follow-up, and regardless of treatment arm, 564 MRD-evaluable patients who were MRD negative at the end of induction had significantly greater probability of progression-free survival (PFS) than did 70 patients who were MRD positive at the end of induction (about 80% vs. 50%; hazard ratio, 0.38), Christiane Pott, MD, reported at the annual meeting of the American Society of Hematology.

GALLIUM participants were adults with follicular lymphoma requiring treatment. They were randomized to receive standard chemotherapy in combination with 6-8 cycles of either intravenous obinutuzumab at a dose of 1,000 mg on days 1, 8, and 15 of cycle 1 and on day 1 of the remaining cycles or intravenous rituximab at a dose of 375mg/m2 on day 1 of each cycle. Responders in each group received their assigned antibody as maintenance every 2 months for up to 2 years, said Dr. Pott, of University Hospital of Schleswig‐Holstein, Kiel, Germany.

Of 324 MRD-evaluable patients in the obinutuzumab arm who continued on maintenance treatment, 300 (92.6%) were MRD-negative at the end of induction, compared with 264 of 310 (85.2%) in the rituximab arm.

The majority of the MRD-negative patients remained negative during maintenance, including 67% of patients receiving obinutuzumab and 63.2% of patient receiving rituximab, she said. There was no difference seen in the relapse rate between groups – 6.3% vs. 6.1%, respectively.

The rate of disease progression or death was 11.4% in the obinutuzumab arm and 15.5% in the rituximab arm.

Additionally, 24 patients in the obinutuzumab arm and 46 in the rituximab arm were MRD positive at the end of induction but were eligible for maintenance therapy based on clinical response; of these, 22 (92%) and 36 (78%), respectively, achieved MRD negativity during maintenance, with 18 and 27 patients in the arms, respectively, achieving MRD negativity within the first 4 months of maintenance therapy, she said.

Of the 12 patients who never achieved an MRD response, 8 progressed or died within 7 months after the end of induction, 1 progressed after 15 months, 1 progressed after 26 months, and 2 remained MRD positive during maintenance up to month 8 and month 12, respectively, but had no documented tumor progression until day 1,348 and day 1,709.

“MRD status reflects the depth of response to treatment and provides insight regarding prognosis after first-line therapy in patients with follicular lymphoma,” Dr. Pott said in an interview, adding that “the findings of the current analysis demonstrate the prognostic value of MRD response assessments in previously untreated follicular lymphoma patients receiving immunochemotherapy.”

Further, the finding that a majority of patients who were MRD positive at the end of induction achieved MRD negativity during the first 4 months of maintenance is likely indicative of the efficacy of continued treatment, and it also suggests that response kinetics can be slower than in patients with an early MRD response at midinduction, she said.

“Also, responses that are beyond the sensitivity of the MRD assay may be less deep,” she added, noting that patients who failed to achieve MRD negativity at the end of induction or during early maintenance had a high chance of experiencing early progression or death.

The findings have implications for individualized treatment based on patient response, as well as for future clinical trial design, she said.

For example, MRD status could allow for earlier identification of patients with poor prognosis who aren’t likely to benefit from maintenance therapy. In clinical trials, it could be used to assess the efficiency of new treatments and to stratify patients based on the likelihood of response, allowing for the evaluation of different treatments in those groups, she explained.

“That would be a very important step in the direction of tailored therapies,” she said, adding that patients with follicular lymphoma tend to have very long PFS, and earlier outcomes parameters or tools beyond clinical parameters for assessing treatment efficiency are needed.

“I hope that future trials will address MRD-based treatment stratification as the adverse prognosis we detect by residual disease might be overcome by an MRD-based switch of patients to more effective and efficient treatments, including novel drugs,” she said.

The GALLIUM study is supported by F. Hoffmann–La Roche. Dr. Pott reported having no financial disclosures.

SOURCE: Pott C et al. ASH 2018, Abstract 396.

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