Venetoclax Monotherapy Demonstrates Deep, Durable Responses Among Adult Patients With R/R CLL

According to phase 3b results, venetoclax monotherapy demonstrates deep and durable responses among adult patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL), including B-cell receptor-associated kinase inhibitor (BCRi)-pretreated patients.

This multicenter, open-label, single-arm, phase 3b trial, titled VENICE-1, included 258 patients aged 18 years or older with previously treated R/R CLL; The presence of del(17p) or TP53 aberrations and previous BCRi treatment were permitted. Patients received a 5-week ramp-up to 400 mg of oral venetoclax once daily, and were treated for up to 108 weeks. This was followed by 2 years of follow-up after discontinuation, or optional extended access.

The primary activity endpoint was complete remission rate (CRR) (CR or CR with incomplete marrow recovery) in BCRi-naive patients, and analyses used intent-to-treat (ex: all enrolled patients, which coincided with those who received at least one dose of venetoclax). It was noted that the median follow-up in the overall cohort was 49.5 months ([interquartile range] IQR 47.2 to 54.1), 49.2 months (47.2 to 53.2) in the BCRi-naive group, and 49.7 months (47.4 to 54.3) in the BCRi-pretreated group.

Study results demonstrated that of 191 BCRi-naive patients, 66 (35%; 95% [confidence interval] CI, 27.8 to 41.8) had CR or CR with incomplete marrow recovery. Additionally, 18 (27%; 95% CI, 16.8 to 39.1) of 67 patients in the BCRi-pretreated group had CR or CR with incomplete marrow recovery. The overall median duration of response for patients who had a response (205 patients; 1 patient included in the overall response rate analysis was excluded from the duration of response analysis due to a data collection discrepancy) was 25.1 months (95% CI, 19.4 to 28.6). The median duration of response was 24.4 months (95% CI 18.1 to 27.9) in the BCRi-naive group (162 patients) and 28.6 months (95% CI, 16.8 to 45.3) in the BCRi-pretreated population (43 patients).

Furthermore, in the overall patient cohort, 92 (36%) patients achieved progression-free survival (PFS), with a median PFS of 28.3 months (95% CI 22.2 to 30.5). In the BCRi-naive group, 63 (33%) of 191 patients had PFS events and in the BCRi-pretreated group, 29 (43%) of 67 had PFSl events. The median PFSl was 28.8 months (95% CI, 22.2 to 31.8) and 23.4 months (95% CI, 16.8 to 33.8), respectively. It was noted that the 5-year survival estimates were 71% (95% CI, 65 to 76.5), 75% (95% CI, 67.5 to 80.6), and 61% (95% CI 47.7 to 71.6) for the overall, BCRi-naive, and BCRi-experienced patients, respectively.

Safety measurements revealed that grade 3 or worse treatment-emergent adverse events were seen in 203 (79%) patients and serious adverse events were reported in 136 (53%) of 258 patients in the overall cohort. The most common treatment-emergent adverse event was neutropenia (96 [37%]) and the most common and serious adverse event was pneumonia (21 [8%]). There were 13 (5%) deaths reported due to adverse events, and 1 of these deaths (autoimmune hemolytic anemia) was possibly related to venetoclax.

Arnon P Kater, MD, Department of Hematology, Cancer Center Amsterdam, Amsterdam, Netherlands, and colleagues concluded, “This phase 3b trial VENICE-1 indicates venetoclax monotherapy can have deep and durable responses in patients with relapsed or refractory chronic lymphocytic leukemia, including BCRi-pretreated patients.”

“High rates of complete remission or complete remission with incomplete marrow recovery were observed over long-term follow-up, with no new safety signals identified,” they added.

Source:

Kater A, Arslan Ö, Demirkan F, et al. Activity of venetoclax in patients with relapsed or refractory chronic lymphocytic leukemia: analysis of the VENICE-1 multicentre, open-label, single-arm, phase 3b trial. Lancet Oncol (2024) 25 (4): 463-473. doi: 10.1016/S1470-2045(24)00070-6