RWE on the Efficacy of Venetoclax-Based Regimens in CLL Match Clinical Trial Data

Rozina Chowdhery, MD

IIn real-world (RW) community settings, venetoclax (Venclexta)-based regimens are effective for the treatment of chronic lymphocytic leukemia (CLL). These regimens are associated with low rates of treatment initiation and significantly prolong time to next treatment or death (TTNT-D), according to RW findings presented at the International Society for Pharmacoeconomics and Outcomes Research (iSPOR) 2023 Meeting.¹

“Real-world analysis is vital to the community oncologist who may not have the idealized patient that is allowed in clinical trials. Often the restrictive inclusion criteria would prohibit enrollment of the average patient walking into your office,” Rozina Chowdhery, MD, hematologist/oncologist, Northwest Cancer Centers- Crown Point, told Targeted Oncology™

Venetoclax in the tablet formulation was granted FDA approval in 2016 for the treatment of patients with CLL with 17p deletion, as detected by an FDA-approved test, who have received at least 1 prior therapy.² Full approval was granted in 2018, based on results from the phase 3 MURANO trial (NCT02005471), in which progression-free survival (PFS) benefit was demonstrated with venetoclax plus rituximab (Rituxan; VenR) vs bendamustine plus rituximab.³

Later, venetoclax was granted approval in combination with obinutuzumab (Gazyva; VenO) based on the PFS benefit shown with the combination compared with chlorambucil and obinutuzumab in the CLL14 study (NCT02242942). This was the first chemotherapy-free venetoclax-based regimen. Although the substantial PFS benefit of venetoclax-based regimens have been well-outlined in clinical trials, no evidence on the effectiveness of these regimens in the RW setting was available.⁴

During iSPOR, results presented in a poster were the first and largest body of evidence showing the efficacy of venetoclax-based regimens in the RW setting. The study was retrospective and observational, and looked at data from the ConcertAI RWD360 database. The information gathered from the database was de-identified electronic health records (EHR) from community practices across 35 states in the United States. The de-identified EHR data were from the clinical charts of patients.¹

The EHRs eligible to be included in the analysis were those of patients with CLL treated at a community practice with a venetoclax-based regimen in the first-line to second-line setting on or before April 30, 2021.

The end points of the study were determining median duration therapy (mDOT), mTTNT-D, the percentage of patients receiving each venetoclax-based regimen, and the percentage of patients who did not receive subsequent therapy.

Baseline characteristics were categorized by the venetoclax-based regimen received and the line of therapy. Of those treated in the first-line setting, the median age was 65.5 years for those treated with VenO, 72 years for those who received VenR, and 69.5 years for those treated with venetoclax monotherapy. Most patients treated with VenO were male, but the majority of those who received either VenR or venetoclax monotherapy were female.

Of the patients treated with a venetoclax-based regimen in the second-line setting, the median age among those treated with VenO was 73.0 years. Patients treated with VenR or monotherapy had a mean age of 66.5 years and 67.0 years, respectively.

In the overall study population, most patients were White and non-Hispanic, and the largest percent of patients were treated in the South.

A total of 128 patients treated with a venetoclax-based regimen in the first-line setting, and VenO was the most common regimen received. A total of 126 patients with CLL were administered a venetoclax-based regimen in the second-line setting, and the most common regimen was venetoclax monotherapy. Notably, 62% of these patients were previously treated with a Bruton’s tyrosine kinase inhibitor.

According to the study results from those treated in the first-line setting, 73.4% of patients did not have subsequent therapy, and notably 93.0% of patients who received VenO did not require subsequent therapy. The mDOT was 12.7 months among the VenO-treated population, 19 months among those treated with VenR, and 3.3 months with monotherapy.

At a median follow-up of 23.1 months, TTNT-D was not reached among patients treated with either VenO or VenR. For patients treated with venetoclax monotherapy, the median TTNT-D was 13.5 months.

Findings for patients treated in the second-line setting were similar to those treated upfront. The mDOT in patients treated with VenO, VenR, and monotherapy was 22.1 months, 12.1 months, and 9.5 months, respectively.

The median follow-up was 27.5 months, among patients treated in the second-line setting, and TTNT-D was not reached for patients who received VenO or VenR. With venetoclax monotherapy, the TTNT-D was 27.9 months.

“The findings are significant in showing the tolerability, efficacy, and sustainable use of venetoclax in actual clinical practice. This study also provides further evidence that time-limited venetoclax combinations work in real-world practice,” said Chowdhery.

_REFERENCES:

_{1. Zakeri M, Emechebe N2, Chowdhery R, et al. Real-world effectiveness and treatment patterns of venetoclax-based regimens among patients with chronic lymphocytic Leukemia (CLL) treated in community settings. Presented at: 2023 International Society for Pharmacoeconomics and Outcomes Research; May 7-10, 2023. Boston, MA. Abstract CO210.}

_{2. FDA approves new drug for chronic lymphocytic leukemia in patients with a specific chromosomal abnormality. News release. FDA. April 11, 2016. Accessed May 10, 2023. https://bit.ly/42MguPV}

_{3. FDA approves venetoclax for CLL or SLL, with or without 17 p deletion, after one prior therapy. News release. FDA. June 8, 2018. Accessed May 10, 2023.}

_{4. FDA approves venetoclax for CLL and SLL. News release. FDA. May 15, 2019. Accessed May 10, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-venetoclax-cll-and-sll}