Immunochemotherapy With Obinutuzumab or Rituximab for Previously Untreated Follicular Lymphoma in the GALLIUM Study: Influence of Chemotherapy on Efficacy and Safety
Purpose;
The GALLIUM study (ClinicalTrials.gov identifier: NCT01332968) showed that obinutuzumab
(GA101; G) significantly prolonged progression-free survival (PFS) in previously untreated patients
with follicular lymphoma relative to rituximab (R) when combined with cyclophosphamide (C),
doxorubicin, vincristine (V), and prednisone (P; CHOP); CVP; or bendamustine. This report focuses
on the impact of chemotherapy backbone on efficacy and safety.
Patients and Methods:
A total of 1,202 patients with previously untreated follicular lymphoma (grades 1 to 3a), advanced
disease (stage III or IV, or stage II with tumor diameter $ 7 cm), Eastern Cooperative Oncology
Group performance status 0 to 2, and requiring treatment were randomly assigned 1:1 to G
1,000 mg on days 1, 8, and 15 of cycle 1 and day 1 of subsequent cycles or R 375 mg/m2 on day 1 of
each cycle, for six to eight cycles, depending on chemotherapy (allocated nonrandomly by center).
Responding patients received G or R for 2 years or until disease progression.
Results:
Baseline Follicular Lymphoma International Prognostic Index risk, bulky disease, and comorbidities differed
by chemotherapy. After 41.1 months median follow-up, PFS (primary end point) was superior for G plus
chemotherapy (overall hazard ratio [HR], 0.68; 95% CI, 0.54 to 0.87; P= .0016), with consistent results across
chemotherapy backbones (bendamustine: HR, 0.63; 95% CI, 0.46 to 0.88; CHOP: HR, 0.72; 95% CI, 0.48 to
1.10; CVP: HR, 0.79; 95% CI, 0.42 to 1.47). Grade 3 to 5 adverse events, notably cytopenias, were most
frequent with CHOP. Grade 3 to 5 infections and second neoplasms were most frequent with bendamustine, which was associated with marked and prolonged reductions in T-cell counts. Fatal events were
more frequent in patients treated with bendamustine, possibly reflecting differences in patient risk profiles.
Conclusion:
Improved PFS was observed for G plus chemotherapy for all three chemotherapy backbones. Safety
profiles differed, although comparisons are confounded by nonrandom chemotherapy allocation