Stilgenbauer S, et al. - Researchers report the outcomes of an extended analysis of venetoclax (an orally bioavailable B-cell lymphoma 2 inhibitor) in a total of 158 patients with relapsed/refractory or previously untreated del(17p) chronic lymphocytic leukemia (CLL). Previously, 107 of those were analyzed and, based on their results, the US Food and Drug Administration and European Medicines Agency approved venetoclax for patients with 17p deleted relapsed/refractory chronic lymphocytic leukemia (del[17p] CLL). The remaining 51 were enrolled in a safety expansion cohort. The impact of minimal residual disease (MRD) negativity on outcome is included in this extended analysis on all enrolled patients. With good tolerability, venetoclax achieved durable responses in patients with del(17p) CLL. In this high-risk population, a high rate of blood MRD < 10^-4 was achieved.

Methods

• After an initial dose ramp up, venetoclax 400 mg per day was given to 158 patients with relapsed/refractory or previously untreated (n = 5) del(17p) CLL.
• On the basis of the 2008 International Workshop on Chronic Lymphocytic Leukemia criteria, with monthly physical exams and blood counts, responses were recorded.
• Mandatory computed tomography scan was performed at week 36, after which clinical evaluation was used for assessment.
• When complete remission was suspected, marrow biopsy was performed.
• Flow cytometry was used to assess MRD.

Results

• Data showed that patients had a median of two prior therapies (range: zero to 10 therapies), 71% had TP53 mutation, and 48% had nodes that were ≥ 5 cm.
• The reported median time on venetoclax was 23.1 months (range: 0 to 44.2 months).
• Median time on study was reported to be 26.6 months (range: 0 to 44.2 months).
• Investigator-assessed objective response rate of 77% (122 of 158 patients; 20% complete remission) and estimated progression-free survival at 24 months of 54% (95% CI, 45% to 62%) was reported on all patients.
• Findings showed that for 16 patients who received prior kinase inhibitors, objective response rate was 63% (10 of 16 patients) and 24-month progression-free survival estimate was 50% (95% CI, 25% to 71%).
• By intent-to-treat analysis, MRD below the cutoff of 10^-4in blood was achieved by 48 (30%) of 158 patients.
• Hematologic events were commonly reported as grade 3 and 4 adverse events and managed with supportive care and/or dose adjustments.