Best Practices to Overcoming Challenges in Initiating Venetoclax for Patients with Chronic Lymphocytic Leukemia: Results from a United States Community-Based Healthcare Practitioner Survey

Background:

Initial treatment (tx) for patients (pts) with chronic lymphocytic leukemia (CLL) currently consists of either Bruton's tyrosine kinase inhibitor (BTKi)-based or venetoclax (Ven)-based combination regimens. While both are effective, differences in administration and potential adverse effects exist. BTKi-based regimens are logistically easy with simple administration; but pts must be on continuous tx until disease progression (PD) or toxicity. Over time, cancer cells gradually develop acquired resistance, leading to reduced effectiveness, PD, and the potential for more adverse events. Ven-based combination regimens are often given as a fixed-duration tx (FDT) that selectively binds to B-cell lymphoma 2, achieving deep remission and durable responses, potentially allowing pts to benefit from years off tx; however, some healthcare practitioners (HCPs) still perceive the initiation process to be a barrier to Ven use. How these factors affect tx decisions between these regimens is poorly understood. This study aimed to understand the perspectives of community-based practitioners regarding best practices and challenges when initiating Ven-based regimens as initial tx for CLL.

Methods:

In June 2024, an online cross-sectional survey was completed by hematologists, oncologists, and advanced practice providers in the US. The Aptitude Health Axess Network, comprising HCPs who collaborate as advisors to life science companies to share their knowledge of the oncology market, clinical science, and patient care, was used to recruit providers. HCPs were eligible if they practiced in the community setting, had ≥5 years of practice (post-residency), treated ≥10 pts with CLL per year, currently treat ≥1 patient with CLL with Ven, and either initiated Ven or remained the primary HCP for CLL if the patient was referred out for Ven ramp-up. HCPs were paid a market rate for their time to complete the survey. HCPs were asked about best practices and challenges when starting Ven as initial tx for CLL. Descriptive statistics were used to analyze HCP practice characteristics, best practices, challenges, and tx decision making.

Results:

A total of 1160 HCPs were approached. Among the 103 community HCP respondents, most of whom were physicians (n=94; 91%), almost all (n=97; 94%) reported initiating Ven in their practice. Most HCPs (n=100; 97%) reported having best practices or educational resources that support the successful initiation of Ven at their site. The most commonly reported best practices for successful initiation of Ven included: having a prophylaxis and monitoring protocol (64%); timing of patient visits in relation to laboratory (lab) tests (63%); training of staff (54%); securing stat lab support (53%); creating patient calendars (48%); timing doses to maximize resources/beds (37%); having a multidisciplinary team to support logistics and education (36%); securing transportation and/or lodging support for pts (34%); utilizing pts' local labs (30%); and establishing a Ven initiation champion/coordinator (19%). HCPs were asked to report areas of challenge for Ven initiation (using a 5-point scale [1 = no challenge, 5 = significant challenge]). For each challenge presented, responses were below a mean of 3, indicating that HCPs who implemented Ven in their practices did not find significant challenges in these areas of Ven initiation. Challenges with the highest scores included: concerns about tumor lysis syndrome (TLS; mean: 2.81; standard deviation [SD]: 1.10); patient logistics (mean: 2.51; SD: 1.16); lab monitoring (6-8 hour lab; mean: 2.46; SD: 1.40); and lab turnaround time (mean: 2.46; SD: 1.28). Despite reporting limited challenges with initiating Ven, some HCPs (24/103; 23%) did not discuss FDT with most of their pts. Among HCPs who discussed FDT with their pts, most (62/96; 65%) reported that fewer than half of pts start with FDT.

Conclusions:

In this survey of community-based HCPs who implemented Ven in their practices, most had best practices, infrastructure changes, or educational resources in place at their site to support the successful initiation of Ven. These practices and resources may support areas of higher reported challenges, such as TLS concerns, patient logistics and lab monitoring. As most HCPs reported that fewer than half of their pts start with FDT, planned analyses will delve deeper into shared decision-making methods when discussing tx options with pts.

Jacobs:Beigene: Consultancy, Research Funding, Speakers Bureau; AstraZeneca: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy; SecuraBio: Consultancy; Genentech: Consultancy; Galapagos: Consultancy; Lilly: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Research Funding; Regeneron: Research Funding; Adaptive: Speakers Bureau. Fletcher:Sanofi: Honoraria; Janssen: Honoraria; BMS: Honoraria; SCRI at Willamette Valley Cancer institute: Current Employment; Oncology Associates of Oregon: Current Employment; Genentech: Consultancy; Novartis: Honoraria, Research Funding; Pharmaessentia: Honoraria; Morphosys: Consultancy. Rettew:Sobi: Speakers Bureau; Rigel: Speakers Bureau; Alexion: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau; Tower Health Medical Group: Current Employment. Li:Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company, Research Funding. Eakle:F. Hoffmann-La Roche Ltd: Current holder of stock options in a privately-held company; Genentech/Roche: Current Employment. Shahkarami:Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company; AstraZeneca: Ended employment in the past 24 months. Wang:Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. To:Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Mathias:Health Outcomes Solutions: Current Employment; Genentech: Research Funding. Manigault:Aptitude Health LLC: Current Employment. Burke:AstraZeneca: Consultancy; Kymera: Consultancy; Bristol Myers Squibb: Consultancy; BeiGene: Consultancy; Novartis: Consultancy; Eli Lilly and Company: Honoraria, Other: Food/Beverage ; Nurix: Consultancy; Abbvie: Consultancy; Genmab: Consultancy; SeaGen: Consultancy; Foresight Diagnostics: Consultancy; Genentech/Roche: Consultancy; Regeneron: Consultancy; Adaptive Biotechnologies: Consultancy.