Real-World Management of Patients with Newly Diagnosed Acute Myeloid Leukemia Treated with Venetoclax-Based Regimens: Results from the AML Real World Evidence (ARC) Initiative
Authors: Vachhani Pankit , Wolach Ofir , Garcia Jacqueline S. , Zeidner Joshua F. , Talati Chetasi , Pollyea Daniel A. , Lai Catherine , Moshe Yakir , Abedin Sameem , Lavie David , Zuckerman Tsila , Xavier Marin , Lee Sangmin , Chen Evan , Edwards Wesleigh , Bui Cat N. , Svensson Anders , Kye Steve , Burne Rebecca , Maitland Jessica , Ma Esprit , Montez Melissa , Grunspan Moshe , Goldberg Aaron D 
Published: November 2021

Abstract
Introduction: Venetoclax (VEN) is a novel BCL-2 inhibitor indicated in the US for treatment of newly-diagnosed (ND) acute myeloid leukemia (AML) in adults ≥75 years or with comorbidities precluding use of intensive chemotherapy, in combination with azacitidine (AZA), decitabine (DEC), or low-dose cytarabine (LDAC). Despite widespread clinical use of VEN combinations in ND AML, real-world practice patterns are largely unknown. We set out to explore real-world outcomes and treatment paradigms in ND AML patients treated with VEN-based regimens.
Methods: The AML Real world evidenCe (ARC) Initiative is a multicenter chart review study of adult pts with ND AML treated with VEN-based regimens and matched control pts (by age and ELN risk) from different academic sites in the US (10 sites) and Israel (4 sites), assessing real-world outcomes as well as VEN treatment practices. Interim descriptive results with data cutoff of 17 May 2021 are presented; data collection is ongoing, with a targeted sample size of over 250 VEN pts and further global expansion planned. Descriptive results are presented here on VEN-related treatment practices overall, and separately in the US and Israel.
Results: At data cutoff, 133 VEN ND AML pts were included. The majority of pts were treated at US sites (102 pts, 76.7%). Regimens administered were VEN+AZA (106 pts, 79.7%), VEN+DEC (24 pts, 18.0%), and VEN+LDAC (3 pts, 2.3%). In Israel, all pts were treated with VEN+AZA (31 pts, 100.0%). Median age was 73.2 years, and the majority of pts (64.7%) had adverse ELN risk. Common genetic mutations observed included TP53 (30 pts, 22.7%), RUNX1 (21 pts,15.9%), IDH1/IDH2 (22 pts, 16.5%), NPM1 (15 pts, 11.4%), and FLT3 ITD (12 pts, 9.1%).
Mean [median] duration of follow-up was 9.2 months [7.1] and duration of VEN-based treatment was 6.9 months [4.1]. 27.8% of pts had discontinued VEN. Among those who discontinued (37 pts), reasons for discontinuation included intolerance (13/37 pts, 35.1%), relapse (8/37 pts, 21.6%), and insufficient response (7/37 pts, 18.9%; results not shown). Unplanned dose interruptions during therapy were observed for 40 pts (30.1%) with common reasons including severe febrile neutropenia (13/40 pts, 32.5%), neutropenia (severe: 10/40 pts, 25.0%; non-severe: 5/40 pts, 12.5%), and patient request (6/40 pts, 15.0%).
Venetoclax ramp-up was performed for 74.4% of pts overall and was more common in Israel (29 pts, 93.5%) than US sites (70 pts 68.6%). Among pts with venetoclax ramp-up performed, the majority received initial VEN treatment in the inpatient setting (US: 47/70 pts, 67.1%; Israel: 25/29 pts 86.2%), median starting and ending doses were 100mg and 400mg respectively, and median ramp-up duration was 3 days; which was similar in the US and Israel. Antifungal use during the first cycle, either prophylactically or in response to an infection, was observed in two-thirds of pts (88 pts, 66.2%) and was more common in the US (72 pts, 70.6%). Among pts with prophylactic antifungal use of a strong CYP3A4 inhibitor (33 pts, 24.8%), 42.4% of pts did not ramp-up and started and maintained a venetoclax dose of 100mg.
At data cutoff, 120 pts had laboratory testing and bone marrow assessment results available in the full sample. Of these pts, timing of first bone marrow biopsy assessments varied, with 44.5% of pts having an assessment in their first cycle of venetoclax and 11.8% of pts having an assessment after the first two cycles. In Israel, a higher proportion of pts had a bone marrow assessment during their first cycle of venetoclax (18 pts, 58.1%). Out of those with response assessed (111 pts, 90.2%), 65.8% of pts achieved a response of CR, CRh, or CRi (US: 54/86 pts, 62.8%; Israel: 19/25 pts, 76.0%).
Conclusions: The ongoing ARC Initiative provides insights on real-world treatment practices and management of ND AML pts treated with VEN-based regimens from academic sites. The ramp-up and dosing patterns appear consistent with label, with some variation. Delay in timing of bone marrow assessments may affect the assessment of time to response and post-response management in the real-world. Additional data collection in the ARC Initiative will provide more robust and valuable insights into VEN-based treatment practices and management in the real world.
Figure 1 Figure 1.

Disclosures
Vachhani: Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Blueprint Medicines: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees. Wolach: AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Neopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding. Garcia: AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding; Pfizer: Research Funding; Prelude: Research Funding; AstraZeneca: Research Funding. Talati: Pfizer: Honoraria; AbbVie: Honoraria; BMS: Honoraria; Jazz: Speakers Bureau; Astellas: Speakers Bureau. Pollyea: Takeda: Consultancy; Daiichi Sankyo: Consultancy; Syndax: Consultancy; Karyopharm: Consultancy; Novartis: Consultancy; AbbVie: Consultancy, Research Funding; Agios: Consultancy; Glycomimetics: Other; Amgen: Consultancy; Janssen: Consultancy; Genentech: Consultancy; Celgene/BMS: Consultancy; Pfizer: Consultancy. Lai: Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Daiichi-Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees; Macrogenics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astellas: Speakers Bureau; Jazz Pharma: Speakers Bureau; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees. Moshe: Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Lectures; Astellas: Membership on an entity's Board of Directors or advisory committees, Other: Lectures; AbbVie: Membership on an entity's Board of Directors or advisory committees, Other: Lectures. Abedin: Agios: Honoraria; Actinium: Research Funding; AltruBio: Research Funding; Helsinn: Research Funding; Pfizer: Research Funding; Amgen: Honoraria; Astellas Pharma Inc.: Research Funding. Lavie: AbbVie: Membership on an entity's Board of Directors or advisory committees, Other: Fees for lectures; BMS: Membership on an entity's Board of Directors or advisory committees; Takeda: Other: Fees for lectures; Roche: Other: Fees for lectures; Novartis: Other: Fees for lectures; Takeda: Consultancy. Zuckerman: Cellect Biotechnology: Honoraria; Gilead Sciences: Honoraria, Speakers Bureau; Novartis: Honoraria; Janssen: Honoraria; BioSight Ltd: Honoraria; Orgenesis Inc.: Honoraria; AbbVie: Honoraria. Xavier: AbbVie: Consultancy, Speakers Bureau; Morphosys/Incyte: Speakers Bureau; Jansen/Pharmacyclics: Honoraria; ADC Therapeutics: Speakers Bureau; Epizyme: Speakers Bureau; Genentech: Honoraria; Kite/Gilead: Honoraria; Beigene: Speakers Bureau; Acrotec: Consultancy; Seattle Genetics: Speakers Bureau; AstraZeneca: Honoraria, Speakers Bureau; Verastem: Honoraria; Celgene/BMS: Speakers Bureau. Lee: Pin Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Innate: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees. Bui: Abbvie: Current Employment, Other: May hold equity. Svensson: AbbVie: Current Employment, Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company. Kye: AbbVie: Current Employment, Other: May hold equity. Burne: Analysis Group Inc: Current Employment, Other: Analysis Group Inc received consulting funds from AbbVie. Maitland: Analysis Group Inc: Current Employment, Other: Analysis Group Inc received consulting funds from AbbVie. Ma: Genentech, Inc.: Current Employment, Other: May hold equity. Montez: Genentech, Inc: Current Employment, Other: May hold equity. Grunspan: AbbVie: Current Employment, Other: May hold equity. Goldberg: AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Arog: Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Research Funding; Aptose: Consultancy, Research Funding; Aprea: Research Funding; DAVA Oncology: Honoraria; Celularity: Research Funding; Prelude Therapeutics: Research Funding; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees.