Venetoclax Plus Ibrutinib Offers 'Generally Favorable' Safety Profile in CLL

A study has compared venetoclax plus ibrutinib with alternative treatments for chronic lymphocytic leukemia (CLL). The results were presented at the Twelfth Annual Meeting of the Society of Hematologic Oncology  in Houston, Texas.

“Venetoclax-ibrutinib combination therapy demonstrates superior efficacy in terms of [progression-free survival (PFS)] and [measurable residual disease (MRD)] compared to alternative treatments in CLL patients,” wrote study coauthors Lokman Hekim Tanrıverdi, MD, PhD, and Ahmet Sarıcı, MD, of İnönü University in Malatya, Turkey.

The coauthors searched four clinical research databases and identified three randomized, controlled trials that compared the venetoclax plus ibrutinib regimen with alternative treatments. Two of the trials investigated venetoclax plus ibrutinib, and a third trial is currently evaluating a triplet containing that doublet plus obinutuzumab. The trials had a total combined cohort of 1,046 patients.

In PFS risk ratio (RR) calculations, venetoclax plus ibrutinib was found to be superior to control regimens: at 12 months with an RR of 1.10, at 24 months with an RR of 1.21, at 36 months with an RR of 1.27, and at 48 months with an RR of 1.47. It was not superior at 60 months, having an RR of 1.74. Subgroup analysis based on presence of immunoglobulin heavy-chain variable region gene mutation, found possible differences in PFS only at 24 months (P<.01).

The study also found that overall survival with venetoclax plus ibrutinib versus controls was comparable at 36 months, with an RR of 1.01. The doublet also significantly reduced MRD in both peripheral blood and bone marrow, with calculated RRs of 1.54 and 1.79, respectively.

The coauthors concluded that venetoclax plus ibrutinib has a “generally favorable” safety profile. It was associated with lower rates of mortality and serious adverse events than the control regimens, with RRs of 0.49 and 0.86, respectively. However, the doublet was not associated with lower pneumonia rates, having an RR of 1.36. It also was associated with greater incidence of diarrhea and hypertension than the control regimens.

Reference

Tanrıverdi LH, Sarıcı A. Venetoclax plus ibrutinib as first-line treatment in patients with chronic lymphocytic leukemia: meta-analysis of randomised controlled trials. Abstract #CLL-247. Presented at the Twelfth Annual Meeting of the Society of Hematologic Oncology; September 4-7, 2024; Houston, Texas.