Study: Venetoclax-Obinutuzumab Improves Progression-Free Survival in Untreated Chronic Lymphocytic Leukemia

In the recent CLL14 study, patients with untreated chronic lymphocytic leukemia (CLL) and coexisting conditions were randomized to receive either 12 cycles of venetoclax-obinutuzumab (Ven-Obi, n = 216) or chlorambucil-obinutuzumab (Clb-Obi, n = 216). The study found that Ven-Obi resulted in superior progression-free survival (PFS) and time-to-next-treatment (TTNT) compared with Clb-Obi, with a higher rate of undetectable minimal residual disease and improved quality of life outcomes.

The treatment of CLL in patients with comorbid conditions presents a challenge, as these patients often cannot tolerate traditional chemotherapy. Venetoclax and obinutuzumab have emerged as effective therapies for untreated CLL, but their long-term benefits compared to chemoimmunotherapy regimens like chlorambucil-obinutuzumab have not been fully established. This study was designed to assess the efficacy of a fixed-duration venetoclax-obinutuzumab regimen compared to a standard chlorambucil-based regimen in terms of progression-free survival, overall survival, and quality of life.

In this multicenter, randomized phase 3 study, patients with untreated CLL and coexisting conditions were assigned to either the Ven-Obi or Clb-Obi group. The primary endpoint was progression-free survival, with secondary endpoints including TTNT, overall survival, rates of undetectable minimal residual disease, adverse events, and quality of life.

At a median follow-up of 76.4 months, the Ven-Obi group showed superior PFS (76.2 months) compared to the Clb-Obi group (36.4 months), with a hazard ratio (HR) of 0.40 (95% CI, 0.31-0.52; P < .0001). Additionally, the 6-year TTNT was longer in the Ven-Obi group (65.2% vs. 37.1%; HR, 0.44; 95% CI, 0.33-0.58; P < .0001).

For overall survival, the Ven-Obi group had a 6-year survival rate of 78.7%, compared with 69.2% in the Clb-Obi group, though the difference did not reach statistical significance (HR, 0.69; 95% CI, 0.48-1.01; P = .052). The Ven-Obi group also had a longer time to definitive deterioration in global health status and quality of life (median, 82.1 vs. 65.1 months; HR, 0.70; 95% CI, 0.51-0.97).

Although both groups had a low incidence of second primary malignancies, the rates were slightly higher in the Ven-Obi group (2.3 vs. 1.4 per 1000 patient-months).

"The sustained long-term survival and quality of life benefits support the use of 1-year fixed-duration venetocluzumab-obinutuzumab in chronic lymphocytic leukemia,” the study authors concluded.

Reference

Al-Sawwaf O, Robrecht S, Zhang C, et al. Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia. Blood. 2024;144(18):1924-1935. doi:10.1182/blood.202402463