Real-World Data Support Safety, Efficacy of Venetoclax for CLL

Venetoclax (Venclexta; Abbvie and Genentech) therapy in patients with chronic lymphocytic leukemia (CLL) showed similar efficacy and safety in the real-world (RW) setting as in the clinical trial setting, a recent study found.

The authors of the new report noted that the data also show that tumor lysis syndrome was not a clinical challenge in the real-world setting. The study was published in Advances in Hematology.1

A decade’s worth of data shows targeted therapies like the BCL-2 inhibitor venetoclax are superior to chemoimmunotherapy in patients with CLL, the authors explained. For instance, the phase 3 MURANO trial (NCT02005471) of venetoclax in combination with rituximab (Rituxan; Genentech and Biogen) outperformed bendamustine with rituximab in patients with relapsed or refractory disease.2 In that trial, patients receiving venetoclax and rituximab had a 2-year progression-free survival rate of 84.9%, compared with 36.3% among the rituximab-bendamustine group.

Real-world outcomes of venetoclax treatment were similar to those seen in clinical trials in patients with chronic lymphocytic leukemia | Image Credit: tippapatt - stock.adobe.com

Yet, clinical trials have strict inclusion criteria that narrow the range of patients eligible for inclusion, the authors of the new study noted.1 Real-world studies, on the other hand, can reflect more diverse populations and give a better sense of how a therapy might perform in the clinic.

“As venetoclax has emerged as a pivotal treatment for CLL, the demand for RW evidence to validate its efficacy and safety has grown significantly,” they wrote.

The investigators used medical records to identify patients with CLL or small lymphocytic lymphoma (SLL) who were treated with venetoclax at Zealand University Hospital in Denmark between April 2017 and January 2023. All of the participants selected for the study were at least 18 years old. Patients with verified Richter transformation prior to the initiation of venetoclax were excluded from the trial.

The investigators identified 821 patients with CLL or SLL. Of those, a total of 112 patients were treated with venetoclax. Seventy-four of those patients were treated following standard clinical protocols (RW cohort) and 38 were treated as part of a randomized controlled trial (RCT cohort). The 2 cohorts had similar demographics; 69% of the RW cohort were men, compared with 76% of the RCT cohort. The RW cohort had a median age of 74 years, compared with 70 years in the RCT cohort.

The RCT cohort had a slightly higher rate of treatment-naive participants (45%) compared with the RW cohort (31%).

Following treatment, both groups had similar efficacy and safety outcomes. The overall response rate (ORR) for the entire study population was 94%, and 74% of patients achieved a complete response. The authors noted that 3 patients in the non-RCT cohort were excluded from the response analysis because they prematurely discontinued venetoclax while at a very low dose level. All of the patients in the RCT cohort achieved a response, compared with 91% of patients in the RW cohort.

In terms of safety, 58% of patients in the RCT group experienced grade 3 or 4 adverse events, compared with 63% in the RW group. Pneumonia and neutropenia were the most common grade 3-4 adverse events. Infections were more common in the RW group, with 29 patients experiencing a grade 3 or 4 infection, compared with 9 patients in the RCT cohort. The authors noted that prophylactic antibiotics should be carefully considered when treating patients with venetoclax in a clinic.

Among the RW group, there were no cases of clinical TLS and 2 cases of biochemical TLS, the authors said. They added that routine practice for those real-world patients did not include collecting blood samples at 6 and 12 hours to monitor for TLS, suggesting that the complication was not a major concern.

Ultimately, the authors concluded that “patients with CLL treated with venetoclax in a RW clinical setting exhibit similar efficacy and safety outcomes to those observed in RCTs.”

References

1. Thau S, Poulsen CB, Larsen MK, Pedersen LM. Real-World Safety and Efficacy of Venetoclax in Chronic Lymphocytic Leukemia: A Single-Center Comparative Analysis With Randomized Clinical Trials. Adv Hematol. 2025;2025(1):3910332. doi:10.1155/ah/3910332.

2. Seymour JF, Kipps TJ, Eichhorst B, et al. Venetoclax-Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia. N Engl J Med. 2018;378(12):1107-1120. doi:10.1056/NEJMoa1713976