GAIA/CLL13 phase III 5‑year follow-up: Venetoclax combinations in CLL

Results from the 5‑year follow-up of the randomized, open-label, phase III GAIA/CLL13 (NCT02950051) trial, evaluating fixed-duration venetoclax combinations (venetoclax + rituximab [RV], venetoclax + obinutuzumab [GV], and GV + ibrutinib [GIV]) vs chemoimmunotherapy (CIT) in 926 fit patients with previously untreated chronic lymphocytic leukemia (CLL) without TP53 aberrations, were published in Blood by Fürstenau et al. The co-primary endpoints were the rate of undetectable measurable residual disease (uMRD) in peripheral blood at Month 15 and investigator-assessed progression-free survival (PFS). Results from the GAIA/CLL13 study have previously been published on the Lymphoma Hub.

Key data: At a median follow-up of 63.8 months, 5‑year PFS rates were 81.3%, 69.8%, 57.4%, and 50.7% in the GIV, GV, RV, and CIT groups, respectively. Five-year overall survival (OS) rates were 94.3%, 93.6%, 94.7%, and 90.7%, respectively. Mean change from baseline in global health status (GHS) remained above the minimal important difference (MID) from Month 6 to follow-up in the RV and GV arms, with median times until improvement (TUI) of 5.8 and 5.9 months, respectively. The first mean change from baseline above MID was observed at 15 months in the GIV arm and at 24 months in the CIT arm. 

Key learning: Results suggest that fixed-duration GV and GIV improve PFS vs CIT and RV. Treatment with GV or RV resulted in greater and more rapid quality of life (QoL) improvements compared with CIT. Clinically meaningful improvements in QoL occurred later with GIV than with GV and RV, likely due to a higher treatment-related symptom burden. These results support the use of venetoclax-based therapy as a treatment option for patients with previously untreated CLL.