Venetoclax Monotherapy Shows Deep, Durable Responses in R/R CLL

White blood cells in leukemia, AI Generative: © Катерина Євтехова - stock.adobe.com

Venetoclax (Venclexta) monotherapy delivered deep and durable responses in patients with relapsed or refractory chronic lymphocytic leukemia (CLL), irrespective of prior treatment with a B-cell receptor-associated kinase inhibitor (BCRi), according to findings from the phase 3 VENICE-1 study (NCT02756611).¹

Complete remission (CR) or a CR with incomplete marrow recovery was observed in 66 of 191 BCRi-naive patients (35%; 95% CI, 27.8%-41.8%) at a median follow-up of 49.2 months (range, 47.2-53.2). In the BCRi-pretreated group, 18 of 67 patients (27%; 95% CI, 16.8%-39.1%) experienced a CR or a CR without incomplete marrow recovery at a median follow-up of 49.7 months (range, 47.4-54.3).CR or CR with incomplete marrow recovery at week 48 was 33% (n = 84).

“The complete remission or complete remission with incomplete marrow recovery rate of 27% and overall response rate of 64% suggest encouraging efficacy of venetoclax monotherapy in this BCRi-pretreated population,” study authors wrote.

Regarding safety, grade 3 or higher treatment-emergent adverse events (AEs) were observed in 79% of patients (n = 203), while serious AEs were observed in 53% of patients (n = 136). The most common treatment-emergent AE was neutropenia (37%), and the most common serious AE was pneumonia (8%). Of 13 deaths reported due to AEs, 1 death of autoimmune hemolytic anemia was possibly related to venetoclax treatment.

Forty-eight of 258 patients discontinued venetoclax treatment to enroll in the subsequentstudy, while 48 discontinued treatmentdue to progressive disease, and 39 discontinued due to AEs.

Most patients were male (70%) and White (98%), and the median age was 68 years (IQR, 61-64). Patients received a median of 2 (IQR, 1-3) prior CLL therapies. Of the BCRi-pretreated patient cohort, 50 patients (75%) reveivedibrutinb (Imbruvica), 26 patients (39%) received idelalisib (Zydelig), 2 patients received acalabrutinib (Calquence), and 11 patients received both ibrutinib and idelalisib.

Since its initial FDA approval in 2016 for patients with CLL with a 17p deletion, venetoclax has been tested and approved in various drug combinations, particularly in CLL.² In 2018, venetoclax plus rituximab (Rituxan) was approved for patients with previously treated CLL or small lymphocytic lymphoma (SLL) with or without 17p deletion.³ Additionally, in 2019, venetoclax plus obinutuzumab (Gazvya)became an approved combination for patients with previously untreated CLL or SLL.⁴

A real-world study from Spain published in 2021 found that venetoclax monotherapy delivered an overall response rate (ORR) at 9 months of 79.2% (n = 38).⁵ However, venetoclax appeared to be more effective in combination with rituximab, demonstrating an ORR of 92.3% (n = 24).

REFERENCES:

1. Kater AP, Arslan Ö, Demirkan F, et al. Activity of venetoclax in patients with relapsed or refractory chronic lymphocytic leukaemia: analysis of the VENICE-1 multicentre, open-label, single-arm, phase 3b trial. Lancet Oncol. Published online March 8, 2024. doi:10.1016/S1470-2045(24)00070-6

2. FDA approves venclexta. News release. Drugs.com. April 11, 2026. Accessed March 18, 2024. https://tinyurl.com/ybwjkdmx 

3. Genentech announces FDA approval for Venclexta plus Rituan for people with previously treated chronic lymphocytic leukemia. News release. Genentech. June 8, 2018. Accessed March 18, 2024. https://tinyurl.com/bdzc6fmy 

4. AbbVie announces US FDA approval of Venclexta (Venetoclax) as a chemotherapy-free combination regimen for previously untreated chronic lymphocytic leukemia patients. News release. AbbVie. May 15, 2019. Accessed March 18, 2024. https://tinyurl.com/28vkwswj 

5. Efficacy and safety of treatment venetoclax monotherapy or combined with rituximab in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) in the real-world setting in Spain: the Venares study. Blood (2021) 138 (Supplement 1): 1561.doi: 10.1182/blood-2021-147685