Efficacy and safety analysis of obinutuzumab or rituximab with chemotherapy for previously untreated FL

On 1^st June 2018, a paper on the efficacy and safety outcomes of immunochemotherapy with obinutuzumab (G) or rituximab (R) in previously untreated follicular lymphoma (FL) was published in the Journal of Clinical Oncology by Wolfgang Hiddemann, University Hospital, Ludwig Maximilian University, Munich, and colleagues.

The safety and efficacy analysis came from results of the GALLIUM study (NCT01332968) that compared R and G combined with either cyclophosphamide (C), doxorubicin, vincristine (V) and prednisone (P) (CHOP), CVP or bendamustine.

Study Overview

• N = 1,202 patients with untreated grade 1–3a FL were included in the study.
• Patients were randomized 1:1 to receive either G 1,000 mg on Day 1, 8, and 15 of cycle 1 and day 1 of subsequent cycles or R 375mg/m² on day 1 of 6–8 cycles
  • N = 601 patients received G plus chemotherapy. 47% were male and the median age was 60 years (range, 26–88)
    • N = 345 patients received bendamustine, n = 196 patients received CHOP and n = 60 patients received CVP
  • N = 601 patients received R plus chemotherapy. 47% were male and the median age was 58 years (range, 23–85)
    • N = 341 patients received bendamustine, n = 203 patients received CHOP and n = 57 patients received CVP
  • The primary endpoint was investigator-assessed progression-free survival (INV-PFS)
  • Secondary endpoints included; response rates at end of induction (EOI), overall survival (OS), time-to-next anti-lymphoma treatment (TTNALT) and safety

Key Findings

• Median follow-up = 41.1 months
• INV-PFS was significantly longer for G plus chemotherapy (HR, 0.68; 95% CI, 0.54–0.87, P = 0.0016). This was significant across all three arms of chemotherapy, P = 0.75
• TTNALT was longer for G plus chemotherapy, P = 0.48
• There was no significant difference in response rates at EOI between the two arms
• The most frequent adverse events (AEs) grade ≥3 included for G plus chemotherapy included; neutropenia (n = 265), leucopenia (n = 51), febrile neutropenia (n = 42) and infusion-related reactions (n = 40). 42 deaths were reported
• The most frequent adverse events (AEs) grade ≥3 included for R plus chemotherapy included; neutropenia (n = 226), leucopenia (n = 50), febrile neutropenia (n = 29) and infusion-related reactions (n = 22). 52 deaths were reported

The authors concluded that there was improved efficacy with the G plus chemotherapy treatment arm in patients with previously untreated FL. They noted that cytopenias were reported more frequently with CHOP chemotherapy and more severe infections were reported with bendamustine chemotherapy. Finally, the authors recommended that first-line therapy and subsequent chemotherapy should be considered individually for each patient.