Trotman J, et al. - Given that a longer progression-free survival has been reported after first-line immunochemotherapy with obinutuzumab vs rituximab in patients with follicular lymphoma enrolled in the GALLIUM trial, researchers assessed the prognostic value of PET–CT responses after first-line immunochemotherapy in this secondary analysis. As per results, PET allowed a better response assessment after first-line immunochemotherapy in patients with follicular lymphoma vs contrast-enhanced CT. A platform for investigation of response-adapted therapeutic approaches is offered by PET assessment according to Lugano 2014 response criteria.

Methods

• Previously untreated patients with CD20-positive follicular lymphoma (grades 1–3a; disease stage III/IV, or stage II with largest tumor diameter ≥7 cm) who were aged 18 years or older and met the criteria for needing treatment were recruited for an open-label, parallel-group randomized, phase 3 trial, named GALLIUM.
• In a 1:1 ratio, randomization of eligible patients to the following treatment regimen was done: intravenous administration of obinutuzumab (1000 mg on days 1, 8, and 15 of cycle 1, then day 1 of subsequent cycles) or rituximab (375 mg/m² on day 1 of each cycle), in six 21-day cycles with cyclophosphamide, doxorubicin, vincristine, and prednisone (known as CHOP; oral administration) followed by two 21-day cycles of antibody alone, or eight 21-day cycles cyclophosphamide, vincristine, and prednisone (known as CVP; oral administration), or six 28-day cycles with bendamustine, followed by maintenance antibody every 2 months for up to 2 years.
• Previously, investigator-assessed progression-free survival (primary endpoint of the trial) has been reported.
• Via this secondary analysis, researchers analyzed PET and CT-based responses at end-of-induction therapy as well as their relationship with progression-free and overall survival outcomes in patients with available scans.
• As per protocol, a prospective evaluation of PET scans (mandatory in the first 170 patients enrolled at sites with available PET facilities, and optional afterwards), acquired at baseline and end of induction (PET population), was done by investigators and an independent review committee (IRC) applying International Harmonisation Project (IHP) 2007 response criteria, as well as retrospective assessment by the IRC only applying current Lugano 2014 response criteria.
• Response assessment was done after masking IRC members (but not study investigators) to treatment and clinical outcome.
• Patients who died or progressed (contrast enhanced CT-based assessment of progressive disease or started next anti-lymphoma treatment) before or at end of induction were not included in the landmark analyses.

Results

• Between July 6, 2011 and February 4, 2014, a total of 1,202 patients were enrolled in GALLIUM.
• Of those, 595 were included in the PET population; landmark analysis for progression-free survival included 533 (IHP 2007; prospective analysis), and 508 (Lugano 2014; retrospective analysis).
• At end of induction, PET complete response according to IHP 2007 criteria was achieved in 390 of 595 patients (65.5% [95% CI 61.6–69.4]), and PET complete metabolic response according to Lugano 2014 criteria was achieved in 450 (75.6% [95% CI 72.0–79.0]) patients.
• With a median of 43.3 months of observation (IQR 36.2–51.8) in PET complete responders and in non-complete responders, 2.5-year progression-free survival from end of induction was 87.8% (95% CI 83.9–90.8) and 72.0% (63.1–79.0), respectively, according to IRC-assessed IHP 2007 criteria (hazard ratio [HR] 0.4, 95% CI 0.3–0.6, p < 0.0001).
• In complete metabolic responders and in non-complete metabolic responders, 2.5-year progression-free survival according to Lugano 2014 criteria was 87.4% (95% CI 83.7–90.2) and 54.9% (40.5–67.3; HR 0.2, 95% CI 0.1–0.3, p < 0.0001), respectively.