Results of a large post hoc study showed that the discontinuation of venetoclax (Venclexta; AbbVie and Roche) monotherapy in patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) due to neutropenia, a common hematologic grade 3 plus adverse event (AE) recorded in patients with CLL who receive venetoclax, was rare, at just 1% of the overall study population.1 

The study’s purpose was to evaluate the efficacy of venetoclax monotherapy in participants with R/R CLL, including patients with the 17p deletion or TP53 mutation, as well as those who had received treatment previously with a B-cell receptor inhibitor. The researchers then assessed the fixed duration of venetoclax monotherapy in patients with R/R CLL, both with and without preexisting grade 3 or higher neutropenia. 

The research was funded by AbbVie, and results were presented during the 2020 American Society of Clinical Oncology Virtual Scientific Program. 

The research team analyzed data from patients with R/R CLL in the ongoing phase 3b trials VENICE-I (NCT02756611) and VENICE-II (NCT02980731) who had received 1 or more dose of venetoclax monother-apy. In these trials, grade 4 hematologic AEs and grade 3 or higher neutropenia with infection or fever were managed through manipulation of doses, with either interruption or reduction as necessary. To treat grade 3 or higher neutropenia specifically, the researchers used granulocyte colony-stimulating factor (G-CSF). 

At the June 30, 2019 data cutoff, 9% of patients had grade 3 or higher neutropenia at baseline. Of these patients, 80% had received G-CSF during the study, while 38% of those with lower than grade 3 neutropenia at baseline had received G-CSF. The median duration for venetoclax in the study was approximately 20.2 months (range, 0.1-36.1 months), while the median number of prior CLL therapies was 2 (range, 1-10) for both groups. Serious infections were experienced by 23% of patients in the grade 3 or higher neutropenia groups and 16% of the lower than grade 3 neutropenia groups. However, the most common AEs that led to discontinuation were second primary malignancies (3%), with 1% of patients in the total population discontinuing treatment due to neutropenia/febrile neutropenia. 

The investigators found that patients with preexisting neutropenia could be managed on venetoclax, although use of G-CSF would likely also be required in conjunction with the treatment. Due to the ongoing nature of the trials, the investigators noted that additional data would soon follow.


REFERENCE

Anderson MA, Davids MS, Kater AP, et al. Neutropenia analysis of venetoclax monotherapy in patients with relapsed or refractory chronic lymphocytic leukemia: pooled data from VENICE-I and -II phase IIIb trials. J Clin Oncol. 2020;38(15 suppl; abstr e20011. doi:10.1200/ JCO.2020.38.15_suppl.e20011