Real-world outcome of low-frequency outpatient monitoring for venetoclax initiation in CLL: Single-center experience.

Abstract

e19026 Background: Venetoclax (Ven) is a potential treatment for CLL/SLL. However, tumor lysis syndrome (TLS) concerns and the need for inpatient monitoring have limited its use in the community setting. This is noteworthy as a great proportion of CLL patients are treated in the community. We implemented a novel, low-frequency-monitoring protocol for outpatient Ven initiation in our CLL population and report our experience. Methods: Between 2023 and 2026, we implemented an outpatient Ven initiation ramp up. All patients were initiated on cytoreductive therapy before Ven and continued for 2 weeks post Ven initiation. Ven was initiated when the following criteria were met: 1) absolute lymphocyte count <20,000 K/mL, 2) adenopathy <5 cm by exam, 3) resolution of splenomegaly if present, per exam and 4) CrCl >45mL/min. Once meeting criteria, Ven dosing followed the standard five-week(W) dose escalation protocol. Prophylactic allopurinol was initiated one day prior to W1 during the escalation period. Patients self-administered the initial Ven dose on W1D1 no earlier than 8:00 PM. The following morning (W1D2), patients presented for outpatient evaluation 12 hours after dose administration. Laboratory monitoring included CBC, BMP, calcium, uric acid, and phosphorus levels. If laboratory parameters were without TLS, defined as uric acid >8 mg/dL, potassium >6 mmol/L, phosphorus>4.5 mg/dL, or calcium <7 mg/dL- dose escalation proceeded on W2D1 with repeat laboratory evaluation on W2D2. This monitoring and dose escalation process was repeated weekly through five weeks. The primary endpoint of this study was to assess the safety and tolerability of Ven dose escalation in the outpatient setting. Results: Thirty patients were transitioned to Ven. The median age was 71 years. 30% were IgVH mutated; 60% were unmutated. Cytogenetics classified 53% as low risk and 44% as high-risk. 80% were heavily pre-treated with ≥ 2 prior lines of therapy. 80% received single-agent BTKi as cytoreductive therapy. There was 100% compliance with treatment appointments. No laboratories suggestive of TLS, hospitalizations, treatment/dose escalation interruptions, nor deaths. occurred. 68% of patients had MRD testing within 3 to 11 months after initiation with 24% of patients achieving uMRD. Conclusions: Real world data shows community-based practitioners are more likely to endorse continuous BTKi as compared to fixed-duration Ven. Importantly, depth of response is greater with ven-based therapy as compared to BTKi-based therapy. Our approach demonstrates real-world evidence regarding the ease and safety of initiating single agent Ven in the outpatient setting across a heterogeneous population. Ven-based therapy should be considered a safe, easy to initiate viable option. Additional reporting of similar experiences is encouraged.