Forecasting the durability of overall survival benefit with gemtuzumab ozogamicin in acute myeloid leukemia: A cumulative and time-series meta-analysis.

Abstract

e18525 Background: Gemtuzumab ozogamicin (GO) has demonstrated survival benefits in patients with acute myeloid leukemia (AML across multiple randomized trials and meta-analyses. However, whether the magnitude of this benefit remains stable as evidence continues to accumulate has not been formally evaluated. We applied cumulative and forecast meta-analytic methods to assess the temporal stability and projected durability of the overall survival (OS) benefit associated with GO. Methods: Study-level hazard ratios (HRs) for overall survival were extracted from randomized controlled trials comparing GO-containing regimens with non-GO controls. Random-effects meta-analysis was performed using restricted maximum likelihood estimation. Cumulative meta-analysis was conducted in chronological order to evaluate the evolution of pooled effect estimates over time. Time-series forecasting of cumulative pooled log-HRs was performed using automated ARIMA modeling to project future pooled estimates over a ten-year horizon. Robustness was assessed using prediction intervals and leave-one-out sensitivity analyses. Results: Three randomized trials encompassing patients treated between 2011 and 2019 were included. The pooled random-effects meta-analysis demonstrated a significant OS benefit associated with GO (HR = 0.85, 95% CI 0.78–0.92), with prediction intervals remaining below the null. Cumulative meta-analysis showed early emergence of benefit followed by stabilization of pooled HR estimates without attenuation as additional studies accrued. Forecast modeling projected sustained pooled HRs centered around 0.83–0.85 over the subsequent decade, with forecast intervals consistently excluding unity. Leave-one-out sensitivity analyses confirmed that no single study disproportionately influenced the pooled or forecasted results. Conclusions: Using cumulative and forecast meta-analysis, we demonstrate that the overall survival benefit associated with gemtuzumab ozogamicin in AML has remained stable as evidence has matured and is projected to persist under continuation of historical trends. These findings support the durability and robustness of GO’s survival advantage and illustrate the utility of forecast meta-analysis as a complementary framework for evaluating long-term evidence stability.