Venetoclax monotherapy for patients with R/R CLL: Results from the phase III VENICE-1 trial

Venetoclax combination therapy improves outcomes in patients with relapsed/refractory (R/R) or newly-diagnosed chronic lymphocytic leukemia (CLL).¹ Preliminary results from the VENICE II study showed that venetoclax monotherapy improved quality of life (QoL) in patients with R/R CLL. However, there is still a lack of long-term data on venetoclax monotherapy in patients with R/R CLL, including those with previous B-cell receptor kinase inhibitor (BCRi) treatment.¹

Here we summarize the results from the VENICE-1 trial (NCT02756611) published by Kater et al.¹ in Lancet Oncology.

Study design¹

• This was an open-label, single-arm, multicenter phase IIIb trial in adult patients with R/R CLL.
• Patients received an initial dose of 20 mg oral venetoclax once daily, increasing weekly up to 400 mg once daily, for up to 108 weeks.
• QoL was assessed using:
  • EuroQol 5 Dimensions 5 Levels Questionnaire (EQ-5D-5L).
  • Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) questionnaire.
  • Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale
• The primary efficacy endpoint was the complete remission (CR) or CR with incomplete count recovery (CRi) rate in BCRi-naïve patients.

Key findings¹

Patients

• In total, 258 patients were included (BCRi-naïve, n = 191; BCRi-pretreated, n = 67).
• Median age was 68 years.
• Median follow-up was 49.5, 49.2, and 49.7 months in the overall cohort, the BCRi-naïve cohort, and the BCRi-pretreated cohort, respectively

Response

• In the BCRi-naïve cohort, the CR/CRi rate at Week 48 was 35% (Figure 1).
• Median duration of response was 25.1, 24.4, and 28.6 months in the overall cohort, the BCRi-naïve cohort, and the BCRi-pretreated cohort, respectively

BCRi, B-cell receptor kinase inhibitor.
*Adapted from Kater, et al.¹

Survival outcomes

• Median progression-free survival was 28.3, 28.8, and 23.4 months in the overall cohort, the BCRi-naïve cohort, and the BCRi-pretreated cohort, respectively.
• In total, 70 patients died and median overall survival was not reached in the overall, BCRi-naïve, and BCRi-pretreated cohorts.
• The estimated 5-year overall survival rate was 71%, 75%, and 61% in the overall cohort, the BCRi-naïve cohort, and the BCRi-pretreated cohort, respectively.

Quality of life

• Venetoclax treatment was associated with a mean improvement of 8.5 points and 7.1 points in the EQ-5D-5L visual analog score at Weeks 48 and 108, respectively.
• Mean FACT-Leu subscale scores were improved with mean scores of 6.8 and 6.0 at Weeks 48 and 108, respectively.
• Mean FACIT-F scores also improved from baseline by 4.9 points at Week 48 and 3.3 points at Week 108.

Safety

• Treatment-emergent adverse events (TEAEs) of any grade occurred in 98% of patients.
  • The most common TEAEs of any grade were neutropenia (43%), diarrhea (39%), and nausea (27%).
• Grade ≥3 TEAEs were observed in 79% of patients.
  • The most common Grade ≥3 TEAEs were neutropenia (37%), anemia (13%), and thrombocytopenia (13%).
• Serious TEAEs were reported in 53% of patients.
  • The most frequently observed serious TEAEs were pneumonia (8%) and febrile neutropenia (6%).

Key learnings
Results from the VENICE-1 trial suggest that venetoclax monotherapy is associated with deep and durable response rates in patients with R/R CLL, including those pretreated with BCRis.