Clinical efficacy and tolerability of venetoclax plus rituximab in patients with relapsed or refractory chronic lymphocytic leukemia—a real-world analysis of the Polish Adult Leukemia Study Group

Abstract

The results of the MURANO trial showed encouraging progression-free survival (PFS) and overall survival (OS) in relapsed/refractory chronic lymphocytic leukemia (RR-CLL) patients treated with venetoclax-rituximab (VEN-R). A retrospective analysis was performed to evaluate the efficacy and safety of VEN-R within the Polish Adult Leukemia Study Group (PALG) centers. The study group included 117 patients with RR-CLL (with early relapse after immunochemotherapy or bearing TP53 aberrations) treated with VEN-R in 2019–2023 outside clinical trials. Patients were treated with a median of 2 (range 1–9) previous lines of therapy. Twenty-two participants were previously treated with BTKi (18.8% out of 117). The median follow-up was 20.3 months (range 0.27–39.1). The overall response rate (ORR) was 95.3% in the group of patients in whom a response to treatment was assessed and 86.3% for all patients. Twenty patients (17.1% out of 117) achieved a complete response (CR), 81 (69.2%) achieved a partial response (PR), and in 5 patients (4.3%), disease progression was noted (assessed as the best response during treatment). The median PFS in the whole cohort was 36.97 (95% CI 24.5, not reached) months, and the median OS was not reached (95% CI 27.03, not reached). Thirty-six patients died during the follow-up, 10 (8.5%; 27.8% of deaths) due to COVID-19 infection. All grade neutropenia (n = 87/117, 74.4%; grade 3 or higher n = 67/117, 57.3%) was the most common treatment adverse event. Forty-five patients (38.5%) remained on treatment, and twenty-two (18.8%) completed 24 months of therapy, while it was discontinued in fifty cases (42.7%). In this real-world setting of early access in very high-risk RR-CLL patients, the VEN-R regimen was associated with shorter median PFS compared with the results of the MURANO trial. This outcome, however, could be attributed to patients’ exposure to SARS-CoV-2 infection and the aggressive course of the disease as very high-risk patients, after multiple lines of prior therapies, were included in the Polish Ministry of Health reimbursement program.

A Review of Resistance Mechanisms to Bruton’s Kinase Inhibitors in Chronic Lymphocytic Leukemia

“…Venetoclax is the first approved B-cell lymphoma two inhibitor (BCL2i) for the treatment of CLL. It shows remarkable efficacy in the therapy of both TN and R/R CLL patients [65][66][67]. Currently, venetoclax, together with BTKi, constitute the most important drugs used in CLL treatment.…”

Venetoclax Initiation in Chronic Lymphocytic Leukemia: International Insights and Innovative Approaches for Optimal Patient Care

“…These survival benefits of venetoclax were sustained 3 years after treatment cessation (5-year follow-up), with a median PFS of 53.6 months (venetoclax plus rituximab) compared with 17.0 months (bendamustine plus rituximab; p < 0.0001) [ 17 ]. Compared to the MURANO trial, a real-world analysis from the Polish Adult Leukemia Study group in patients with very high-risk R/R CLL receiving the combination of venetoclax plus rituximab, yielded a shorter median PFS (36.97 months [95% CI 24.5, not reached]) [ 18 ]. The randomized phase 3 CLL14 study (NCT02242942; N = 432) showed a significant decrease in disease progression or death (hazard ratio [HR], 0.35 [ p < 0.001]) and longer PFS at 24-months (88.2% vs. 64.1%) after fixed-duration venetoclax plus obinutuzumab versus chlorambucil plus obinutuzumab in patients with previously untreated CLL and coexisting conditions [ 19 ], leading to FDA and EMA approvals of venetoclax plus obinutuzumab in first-line therapy [ 7 , 8 ].…”