Background: Multiple BTK inhibitors (BTKis) are approved for treating patients with chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), with further approvals expected in the near future, increasing the clinical complexity of decision-making in patient care. This study sought to quantify knowledge and practice gaps among oncology healthcare professionals (HCPs) in the use of BTKis to treat patients with CLL and MCL, with the goal of informing the design of evidence-based education interventions aimed at addressing these gaps.

Methods: From November 2021 - January 2022, 488 eligible HCPs (including physicians, physician assistants, nurse practitioners, and pharmacists) participated in a 2-phase study focused on knowledge and use of BTKis for CLL and MCL. Participants were required to be active practitioners who treated patients with CLL and/or MCL.

In the exploratory qualitative phase of this study, 30 US participants completed a 45-minute telephone interview focusing on factors that influence clinical reasoning in selecting and providing treatment for CLL and MCL. Interviews were transcribed, and thematic analysis was performed. The quantitative phase of this study consisted of an online survey composed of multiple-choice questions and semantic differential rating scales. Respondents' answers to each question in the quantitative survey were compared with optimal answers as identified by treatment guidelines and specialists in CLL and MCL patient care.

Results: Of responding HCPs, 59% were physicians, 64% had been in practice >10 years, 73% practiced in a nonacademic setting, and 73% cared for ≤10 patients with CLL and/or MCL per week. A group of 7 core practice gaps were identified through combined analysis of data from the qualitative and quantitative surveys; these included optimal therapy selection in the first- and later-line settings for CLL and MCL, awareness of mechanisms of resistance to approved BTKi therapy, and knowledge of investigational therapies and appropriate clinical trial referral. For example, of 270 responding HCPs, 47% were unable to select preferred first-line therapy (per expert recommendations) for a patient with CLL and high tumor burden and renal insufficiency, with 9% recommending a chemoimmunotherapy regimen. Likewise, a significant percentage of surveyed HCPs lacked confidence in their approach to therapy selection for patients with relapsed/refractory CLL or MCL, with optimal sequencing identified as a primary concern.

Many HCPs were unfamiliar with BTKi mechanisms of action. Gaps in knowledge were particularly evident with novel BTKis, including pirtobrutinib, with 46% of online survey respondents uncertain about the noncovalent mechanism of this agent and only 33% aware that pirtobrutinib has shown activity in patients with CLL and disease progression on ibrutinib due to the appearance of a BTK C481 mutation. In total, 60% of respondents would not consider recommending a newly approved agent if they were not familiar with the class or mechanism of action of this agent.

Conclusions: Many HCPs lack confidence and knowledge in applying optimal care for patients with CLL and MCL, particularly with regard to the use of BTKis, both in first- and later-line therapy. A lack of familiarity with promising novel BTKis under clinical investigation may lead to missed opportunities to enroll eligible patients on clinical trials and potentially delay integration of these agents into clinical practice as new indications emerge. Results of this study provide evidence to support the design of clinical tools, educational programs, and performance improvement interventions. Detailed findings will be presented, including group-specific analyses and investigation of the causalities of each of the identified practice gaps.

Flowers:National Cancer Institute: Research Funding; Eastern Cooperative Oncology Group: Research Funding; V Foundation, Cancer Prevention and Research Institute of Texas: CPRIT Scholar in Cancer Research: Research Funding; Ziopharm: Research Funding; Xencor: Research Funding; Burroughs Wellcome Fund: Research Funding; Guardant: Research Funding; EMD: Research Funding; Cellectis: Research Funding; Amgen: Research Funding; Allogene: Research Funding; Adaptimmune: Research Funding; NPower: Current holder of stock options in a privately-held company; Acerta: Research Funding; 4D: Research Funding; Spectrum: Consultancy; SeaGen: Consultancy; Pharmacyclics/Janssen: Consultancy; Genmab: Consultancy; Gilead: Consultancy, Research Funding; Karyopharm: Consultancy; Genentech/Roche: Consultancy, Research Funding; Foresight Diagnostics: Consultancy, Current holder of stock options in a privately-held company; Denovo Biopharma: Consultancy; Celgene: Consultancy, Research Funding; Iovance: Research Funding; Janssen Pharmaceutical: Research Funding; Kite: Research Funding; Morphosys: Research Funding; TG Therapeutics: Research Funding; Pfizer: Research Funding; Pharmacyclics: Research Funding; Sanofi: Research Funding; Takeda: Research Funding; BeiGene: Consultancy; Abbvie: Consultancy, Research Funding; Bayer: Consultancy, Research Funding. Sharman:AbbVie: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding; Beigene: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Research Funding; Genentech: Consultancy; TG Therapeutics: Consultancy, Research Funding; Merck: Consultancy; Lilly: Consultancy, Honoraria, Research Funding; Araris Biotech AG: Consultancy, Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Consultancy, Honoraria, Research Funding; Pharmacyclics LLC, an AbbVie Company: Honoraria.

Author notes

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Asterisk with author names denotes non-ASH members.

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