Contributions
Abstract: S148
Type: Oral Presentation
Session title: Clinical trials with targeted therapies in CLL
Background
Early results from ELEVATE-TN (NCT02475681) at a median follow-up of 28.3 months demonstrated superior efficacy of acalabrutinib (A) ± obinutuzumab (O) compared with O + chlorambucil (Clb) in patients with treatment-naïve (TN) chronic lymphocytic leukemia (CLL) (Sharman et al. Lancet 2020;395:1278-91).
Aims
To report the updated efficacy and safety results from the ELEVATE-TN study after a median follow-up duration of 4 years.
Methods
Patients received A±O or O+Clb. Crossover to A monotherapy was permitted in patients who progressed on O+Clb. Investigator-assessed (INV) progression-free survival (PFS), INV overall response rate (ORR), overall survival (OS), and safety were evaluated. Informed consent was obtained from all patients prior to trial enrollment.
Results
A total of 535 patients (A+O, n=179; A, n=179; O+Clb, n=177) were randomized. The median patient age was 70 years; 63% of patients had unmutated IGHV and 9% had del(17p). At a median follow-up of 46.9 months (range, 0.0–59.4; data cutoff: Sept 11, 2020), the median PFS was not reached (NR) for A+O and A patients versus 27.8 months for O+Clb patients (both P<0.0001). In patients with unmutated IGHV, the median PFS was NR (A+O and A) versus 22.2 months among O+Clb patients (both P<0.0001). In patients with del(17p), the median PFS was NR (A+O and A) versus 17.7 months for O+Clb (P<0.005). Estimated 48-month PFS rates were 87% for A+O, 78% for A, and 25% for O+Clb. Median OS was NR in any treatment arm with a trend towards significance in the A+O group (A+O vs O+Clb, P=0.0604); estimated 48-month OS rates were 93% (A+O), 88% (A), and 88% (O+Clb). ORR was significantly higher with A+O (96.1%; 95% CI 92.1–98.1) versus O+Clb (82.5%; 95% CI 76.2–87.4; P<0.0001); ORR with A was 89.9% (95% CI 84.7–93.5; P=0.035 vs O+Clb). Complete response/complete response with incomplete hematologic recovery (CR/CRi) rates were higher with A+O (26.8%/3.9%) versus O+Clb (12.4%/0.6%); 10.6%/0.6% had CR/CRi with A. Common adverse events (AEs) and AEs of interest are shown in the Table. Overall treatment discontinuation rates were 25.1% (A+O), 30.7% (A), and 22.6% (O+Clb); the most common reasons were AEs (12.8%, 12.3%, 14.7%, respectively) and progressive disease (4.5%, 7.8%, 1.7%). Most patients (77.4%) completed O+Clb treatment.
Conclusion
With a median follow-up of 46.9 months (~4 years) in the ELEVATE-TN study, the efficacy and safety of A+O and A monotherapy was maintained, with an increase in CR since the interim analysis (from 21% to 27% [A+O] and from 7% to 11% [A]) and low rates of discontinuation.
Keyword(s): Chronic lymphocytic leukemia, Phase III
Abstract: S148
Type: Oral Presentation
Session title: Clinical trials with targeted therapies in CLL
Background
Early results from ELEVATE-TN (NCT02475681) at a median follow-up of 28.3 months demonstrated superior efficacy of acalabrutinib (A) ± obinutuzumab (O) compared with O + chlorambucil (Clb) in patients with treatment-naïve (TN) chronic lymphocytic leukemia (CLL) (Sharman et al. Lancet 2020;395:1278-91).
Aims
To report the updated efficacy and safety results from the ELEVATE-TN study after a median follow-up duration of 4 years.
Methods
Patients received A±O or O+Clb. Crossover to A monotherapy was permitted in patients who progressed on O+Clb. Investigator-assessed (INV) progression-free survival (PFS), INV overall response rate (ORR), overall survival (OS), and safety were evaluated. Informed consent was obtained from all patients prior to trial enrollment.
Results
A total of 535 patients (A+O, n=179; A, n=179; O+Clb, n=177) were randomized. The median patient age was 70 years; 63% of patients had unmutated IGHV and 9% had del(17p). At a median follow-up of 46.9 months (range, 0.0–59.4; data cutoff: Sept 11, 2020), the median PFS was not reached (NR) for A+O and A patients versus 27.8 months for O+Clb patients (both P<0.0001). In patients with unmutated IGHV, the median PFS was NR (A+O and A) versus 22.2 months among O+Clb patients (both P<0.0001). In patients with del(17p), the median PFS was NR (A+O and A) versus 17.7 months for O+Clb (P<0.005). Estimated 48-month PFS rates were 87% for A+O, 78% for A, and 25% for O+Clb. Median OS was NR in any treatment arm with a trend towards significance in the A+O group (A+O vs O+Clb, P=0.0604); estimated 48-month OS rates were 93% (A+O), 88% (A), and 88% (O+Clb). ORR was significantly higher with A+O (96.1%; 95% CI 92.1–98.1) versus O+Clb (82.5%; 95% CI 76.2–87.4; P<0.0001); ORR with A was 89.9% (95% CI 84.7–93.5; P=0.035 vs O+Clb). Complete response/complete response with incomplete hematologic recovery (CR/CRi) rates were higher with A+O (26.8%/3.9%) versus O+Clb (12.4%/0.6%); 10.6%/0.6% had CR/CRi with A. Common adverse events (AEs) and AEs of interest are shown in the Table. Overall treatment discontinuation rates were 25.1% (A+O), 30.7% (A), and 22.6% (O+Clb); the most common reasons were AEs (12.8%, 12.3%, 14.7%, respectively) and progressive disease (4.5%, 7.8%, 1.7%). Most patients (77.4%) completed O+Clb treatment.
Conclusion
With a median follow-up of 46.9 months (~4 years) in the ELEVATE-TN study, the efficacy and safety of A+O and A monotherapy was maintained, with an increase in CR since the interim analysis (from 21% to 27% [A+O] and from 7% to 11% [A]) and low rates of discontinuation.
Keyword(s): Chronic lymphocytic leukemia, Phase III