Assessing Hematologist's Knowledge of the Use of Ibrutinib and Acalabrutinib in B-Cell Malignancies
Authors: Willis Lauren , Tanzola Melinda , Furman Richard R. 
Published: October 2019

Abstract
Background: The objective of this study was to assess current clinical practices of hematology/oncology (hem/onc) specialists related to BTK inhibitor use in the treatment of patients with mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL), in order to identify knowledge, competency, and practice gaps and barriers to optimal care.
Methods: A continuing medical education (CME)-certified clinical practice assessment consisting of 25 multiple choice questions that were designed to measure knowledge, skills, attitudes, and competence of hem/onc specialists regarding BTK inhibitor use. The survey instrument was made available online to physicians without monetary compensation or charge. Respondent confidentiality was maintained and responses were de-identified and aggregated prior to analyses. The activity launched on May 31, 2018 (after the approval of acalabrutinib for MCL) and participant responses are still being collected at the time of abstract submission.
Results: At the time of this report there are 124 hem/onc activity participants, collection is on-going. Demographics are listed in Table 1 and levels of confidence and barriers to incorporating BTK inhibitors are listed in Table 2.Differentiating Between Ibrutinib and AcalabrutinibVery low recognition of the differences between first and second generation BTK inhibitors.Only 16% identified that both ibrutinib and acalabrutinib target BTK at the same amino acid residue.Barely over a quarter (27%) understand that acalabrutinib irreversibly inhibits BTK, similar to ibrutinib.Higher level of knowledge related to the specificity of second generation BTK inhibitors and the differences in dosing frequency compared to first generation BTK inhibitors, but still room for improvement.Half correctly identified acalabrutinib is potentially better tolerated than ibrutinib due to greater relative selectivity for BTK over EGFR, ITK, and TEC kinases.Over half (56%) demonstrated knowledge of the dosing schedule for ibrutinib and acalabrutinib, while 33% incorrectly think both BTK inhibitors are dosed once a day.Strong recognition of the FDA-approved indication for ibrutinib in MCL (74%) with much less recognition of the FDA-approved indication for acalabrutinib in MCL (35%).BTK MutationsLack of knowledge about how the C481S mutation causes resistance to ibrutinib and acalabrutinib.A little over half (54%) understand that a BTK mutation at position 481 from cysteine to serine results in resistance to both ibrutinib and acalabrutinib.Only 33% demonstrated knowledge of the C481S resistance mechanism.Clinical Trial DataMore familiarity with pivotal phase 3 clinical trial data for ibrutinib, indicating a need for further education about phase 2 acalabrutinib data.69% correctly identified the OS outcome with ibrutinib in previously treated CLL43% correctly identified the ORR with acalabrutinib in previously treated CLL26% correctly identified the ORR with acalabrutinib in previously treated MCL
Conclusions: This activity indicates there are significant gaps in knowledge and confidence as well as barriers impeding hem/onc ability to incorporate BTK inhibitors into the treatment plans for their patients with B-cell malignancies. There is sub-optimal awareness of differences between first and second generation BTK inhibitors as well as trial data for second generation BTK inhibitors. Additional education is needed to improve the knowledge and confidence of academic and community hem/onc specialists who care for patients with CLL and MCL so they are better equipped to utilize BTK inhibitors.

Disclosures
Furman: Acerta: Consultancy, Research Funding; Sunesis: Consultancy; Verastem: Consultancy; TG Therapeutics: Consultancy; Genentech: Consultancy; Incyte: Consultancy, Other: DSMB; Gilead: Consultancy; Loxo Oncology: Consultancy; Pharmacyclics LLC, an AbbVie Company: Consultancy; Janssen: Consultancy; AbbVie: Consultancy.