Management of BTK Inhibitor Associated Adverse Events: Current Practice Trends Among Healthcare Providers and Concordance with Expert Recommendations
Authors: Rosenthal Kristen , Abramson Jeremy S , Awan Farrukh T , Leonard John P. , Vose Julie M. , Quill Timothy A , Flowers Christopher 
Published: November 2020

Introduction: The advent of BTK inhibitors (BTKi; ibrutinib, acalabrutinib, zanubrutinib) has dramatically improved outcomes for many patients with B-cell malignancies including CLL/SLL, MCL, WM, and MZL. To ensure optimal patient outcomes with BTKi therapy, it is essential to maintain both ongoing therapy and patient quality of life. These dual goals require prompt recognition and management of the unique adverse events (AEs) associated with BTKi therapy. An online Interactive Decision Support Tool was developed to provide healthcare providers (HCPs) with case specific guidance on managing BTKi AEs (available at: www.clinicaloptions.com/BTKiTool). Here, we report HCP practice trend data for the management of various BTKi AEs collected with this online tool compared with recommendations from a panel of experts.
Methods: The online tool was developed with input from 5 experts who provided BTKi AE management recommendations for specific patient scenarios. The online tool captured 164 unique clinical scenarios based on criteria including disease type, BTKi used, and the type and severity of the BTKi AE. To use the online tool, HCPs enter information about their patient case and their planned management strategy. The HCPs were then shown the management recommendation from the 5 experts for that specific BTKi AE scenario. After viewing the expert management recommendation, HCPs were asked if it had an impact on their intended management approach.
Results: Between September 2019 and July 2020, 754 unique case scenarios were entered into the BTKi AE tool, with 319 cases related to a specific BTKi AE, by 432 HCPs. Of HCPs who answered the optional demographics questions (n = 96), 65% of cases were entered by clinicians who treat ≤ 10 patients/year with BTKi and 51% of cases entered were for specific patients in their clinical practice. Most cases entered in the tool were for patients with CLL (69%) followed by MCL cases (15%). Cases involving ibrutinib treatment were most common in this analysis (82% of cases) with acalabrutinib treatment entered for the remaining 18% of cases. Zanubrutinib was not yet approved when this tool was created and therefore was not included as a BTKi option.
The most common AEs selected by HCPs using the tool regardless of BTKi therapy were atrial fibrillation, bruising or bleeding, and diarrhea [Figure]. For patient scenarios treated with acalabrutinib, HCPs also frequently selected headache (24%) as an AE of interest [Figure]. Overall, the planned BTKi AE management strategy of HCPs for mild to moderate AEs matched the expert recommendations in 56% of cases with ibrutinib treatment and 79% with acalabrutinib treatment. There was lower concordance between HCPs and experts for the management of grade 3/4 events with either ibrutinib (42%; P &lt; .0001) or acalabrutinib (36%; P &lt; .0001). For example, for patient cases with grade 3/4 atrial fibrillation (n = 49), only 39% of HCPs would hold therapy whereas 41% indicated that they would continue therapy and 14% were unsure how to manage the AE. For HCPs who differed from expert recommendations, only 42% of respondents who entered mild to moderate AEs indicated that the expert recommendations provided by the tool changed their management plan, but 81% of respondents who entered grade 3/4 events would change their management plan.
Conclusions: These data suggest that management of BTKi AEs by HCPs often diverges from evidence-based expert recommendations, especially grade 3/4 AEs. Use of an online tool providing easy access to BTKi AE management recommendations may improve patient care and safety. A detailed analysis of the tool, including case entries and planned management vs expert recommendations will be presented.
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Disclosures
Awan: Blueprint medicines: Consultancy; Celgene: Consultancy; Pharmacyclics: Consultancy; Janssen: Consultancy; Abbvie: Consultancy; Astrazeneca: Consultancy; Sunesis: Consultancy; Karyopharm: Consultancy; MEI Pharma: Consultancy; Genentech: Consultancy; Gilead Sciences: Consultancy; Kite Pharma: Consultancy; Dava Oncology: Consultancy. Leonard:MEI Pharma: Consultancy; Bayer: Consultancy; Gilead/Kite: Consultancy; Karyopharm: Consultancy; GenMab: Consultancy; BMS/Celgene: Consultancy; Roche/Genentech: Consultancy; Epizyme: Consultancy; Sutro: Consultancy; Miltenyi: Consultancy; AstraZeneca: Consultancy; Regeneron: Consultancy; ADC Therapeutics: Consultancy. Vose:AbbVie: Consultancy, Honoraria; Kite, a Gilead Company: Honoraria, Research Funding; Incyte: Research Funding; Novartis: Research Funding; Seattle Genetics: Research Funding; Epizyme: Honoraria, Research Funding; Karyopharm Therapeutics: Consultancy, Honoraria; Allogene: Honoraria; Bristol-Myers Squibb: Research Funding; Miltenyi Biotec: Honoraria; Wugen: Honoraria; Roche/Genetech: Consultancy, Honoraria, Other; Celgene: Honoraria; Loxo: Consultancy, Honoraria, Research Funding; Verastem: Consultancy, Honoraria; Janssen: Honoraria; AstraZeneca: Consultancy, Honoraria, Research Funding. Flowers:Denovo Biopharma: Consultancy; Kite: Research Funding; Celgene: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; OptumRx: Consultancy; Karyopharm: Consultancy; Pharmacyclics/Janssen: Consultancy; Spectrum: Consultancy; Acerta: Research Funding; Millennium/Takeda: Consultancy, Research Funding; TG Therapeutics: Research Funding; Burroughs Wellcome Fund: Research Funding; Eastern Cooperative Oncology Group: Research Funding; National Cancer Institute: Research Funding; V Foundation: Research Funding; Cancer Prevention and Research Institute of Texas: Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; BeiGene: Consultancy; Leukemia and Lymphoma Society: Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy.