Among fit patients with previously untreated chronic lymphocytic leukemia (CLL), fixed-duration venetoclax plus obinutuzumab (GV), without or with ibrutinib (GIV), yields superior progression-free survival (PFS) rates to standard chemoimmunotherapy (CIT), according to research presented at the EHA 2022 Hybrid Congress. No improvements in overall survival (OS) were observed.
Although previous research has shown that GV is associated with positive clinical outcomes among previously untreated, fit patients with CLL, CIT is still the most frequently used regimen. Prior to the current study, there were no data directly comparing GV and GIV to CIT in this patient population.
The GAIA/CLL13 study (ClinicalTrials.gov Identifier: NCT02950051) was designed to compare the efficacy and safety of regimens including venetoclax with CIT. At EHA 2022, the researchers presented the results from a PFS analysis, which was preplanned to take place at month 61.
All included patients had previously untreated CLL with no evidence of TP53 mutations. Researchers randomly assigned patients 1:1:1:1 to receive standard CIT, venetoclax plus rituximab, GV, or GIV. The coprimary endpoints were undetectable minimal residual disease (MRD) and PFS.
Overall, 926 patients were enrolled, of whom 229 were assigned to receive CIT, 237 to the rituximab group, 229 to GV, and 231 to GIV. The median patient age was 61 years, and 56% of patients had no evidence of IGHV mutations.
The median follow-up was 38.8 months. Analysis showed that, compared with CIT, both GV (86.5% vs 52%; P <.0001) and GIV (92.2% vs 52%; P <.0001) improved the rate of undetectable MRD.
Furthermore, compared with CIT, GIV improved PFS (hazard ratio [HR], 0.32; 97.5% CI, 0.19-0.54; P <.0001). A PFS improvement was also noted with GV (HR, 0.42; 97.5% CI, 0.26-0.68; P <.0001).
No PFS improvement was noted with rituximab (HR, 0.79; P =.183). The 3-year PFS rate was 75.5% with CIT, 80.8% with rituximab, 87.7% with GV, and 90.5% with GIV.
No improvements in OS were noted in the GIV (95.3%) and GV (96.3%) groups, compared with CIT (95%).
Grade 3 or higher adverse events were noted in 81.5% of patients in the CIT group, 73% in the rituximab group, 84.2% in the GV group, and 83.5% in the GIV group. Adverse events leading to death were noted in 9 patients in both the GIV and GV groups, and in 10 and 8 patients in the CIT and rituximab groups, respectively.
Disclosures: This research was partly supported by Janssen-Cilag Ltd., Hoffmann-La Roche, and AbbVie. The presenter declared affiliations with Janssen, Gilead, F Hoffmann-La Roche, AbbVie, BeiGene, AstraZeneca, and MSD.
Eichhorst B, Niemann C, Kater A, et al. Time-limited venetoclax-obinutuzumab +/- ibrutinib is superior to chemoimmunotherapy in frontline chronic lymphocytic leukemia (CLL): PFS co-primary endpoint of the randomized phase 3 GAIA/CLL13 trial. Presented at EHA 2022; June 9-12, 2022. Abstract LB2365.