Venetoclax Monotherapy Shows Deep, Durable Responses in R/R CLL
Treatment with venetoclax appeared to improve responses in patients with relapsed or refractory chronic lymphocytic leukemia, according to findings from a phase 3b study.
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
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