Association of early disease progression and very poor survival in the GALLIUM study in follicular lymphoma: benefit of obinutuzumab in reducing the rate of early progression

Abstract

We evaluated early disease progression and its impact on overall survival (OS) in previously untreated follicular lymphoma patients in GALLIUM ( clinicaltrials.gov identifier: 01332968 ), and investigated the effect on early disease progression of the two randomization arms: obinutuzumab-based versus rituximab-based immunochemotherapy. Cause-specific Cox regression was used to estimate the effect of treatment on the risk of disease progression or death due to disease progression within 24 months of randomization and to analyze OS in patients with or without disease progression after 24 months. Mortality in both groups was analyzed 6, 12, and 18 months post randomization (median follow up, 41 months). Fewer early disease progression events occurred in obinutuzumab (57 out of 601) versus rituximab (98 out of 601) immunochemotherapy patients, with an average risk reduction of 46.0% (95%CI: 25.0-61.1%; cumulative incidence rate 10.1% vs . 17.4%). At a median post-progression follow up of 22.6 months, risk of mortality increased markedly following a progression event [HR of time-varying progression status, 25.5 (95%CI: 16.2-40.3)]. Mortality risk was higher the earlier patients progressed within the first 24 months. Age-adjusted HR for OS after 24 months in surviving patients with disease progression versus those without was 12.2 (95%CI: 5.6-26.5). Post-progression survival was similar by treatment arm. In conclusion, obinutuzumab plus chemotherapy was associated with a marked reduction in the rate of early disease progression events relative to rituximab plus chemotherapy. Early disease progression in patients with follicular lymphoma was associated with poor prognosis, with mortality risk higher after earlier progression. Survival post progression did not seem to be influenced by treatment arm.

Sustained Progression-Free Survival Benefit of Rituximab Maintenance in Patients With Follicular Lymphoma: Long-Term Results of the PRIMA Study

“… 28 Whether the recently described progression of disease within 24 months of initiating treatment end point is a more reliable surrogate of OS in patients with FL receiving 1L immunochemotherapy with or without maintenance remains to be established. 29 - 32 …”

Follicular Lymphoma: Recent and Emerging Therapies, Treatment Strategies, and Remaining Unmet Needs

“…Patients with progression of disease within 24 months of completing induction chemoimmunotherapy (POD24), which made up 19% of patients in this data set, had poorer outcomes compared with those with longer remission durations (5‐year overall survival [OS]: 50% vs. 90%, respectively) even after adjustment for Follicular Lymphoma International Prognostic Index (FLIPI) score (discussed below) . These results were validated in the University of Iowa and Mayo Clinic Molecular Epidemiology Resource data sets , and in the GALLIUM study and using the FLASH data set . Additionally, a longer duration from diagnosis to progression (i.e., event‐free survival of >12 months after diagnosis) did not result in excess mortality compared with the age‐ and sex‐matched general population .…”

Rituximab maintenance significantly reduces early follicular lymphoma progressions in patients treated with frontline R‐CHOP

“…Effect of maintenance on POD24 events remains poorly studied. Gallium trial comparing rituximab or obinutuzumab in induction and in subsequent maintenance showed fewer early disease progression events occurred in obinutuzumab versus rituximab immunochemotherapy patients, with an average risk reduction of 46.0% and cumulative incidence rate 10.1% versus 17.4% [26]. However, it is unclear, whether POD24 reduction was caused by higher efficacy of particular obinutuzumab-based induction or due to perhaps more potent obinutuzumab maintenance.…”