-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

4954 Comparison of Patients with Newly Diagnosed (ND) Acute Myeloid Leukemia (AML) Treated with Venetoclax and Hypomethylating Agents Vs Other Therapies By TP53 and IDH1/2 Mutation: Results from the AML Real World Evidence (ARC) Initiative

Program: Oral and Poster Abstracts
Session: 906. Outcomes Research—Myeloid Malignancies: Poster III
Hematology Disease Topics & Pathways:
AML, Acute Myeloid Malignancies, Diseases, Myeloid Malignancies
Monday, December 12, 2022, 6:00 PM-8:00 PM

Ofir Wolach1*, Jacqueline S. Garcia, MD2, Pinkal Desai, MD, MPH3, Pankit Vachhani, MD4, Joshua F. Zeidner, MD5, Sameem Abedin, MD6, Kendra Sweet, MD7, Catherine Lai, MD, MPH8, Yakir Moshe, MD, PhD9*, Daniel A. Pollyea, MD10, Marin Xavier11*, Boaz Nachmias12*, Tsila Zuckerman, MD13, Sangmin Lee14*, Evan C. Chen2*, Srilakshmi Bathini, MD4*, Wesleigh Edwards11, Cat N. Bui, PharmD15*, Wei-Han Cheng, PhD16*, Catherine Miller, PharmD17*, Annie Guerin18*, Jessica Maitland18*, Esprit Ma, MPH19*, Melissa Montez, PharmD19*, Moshe Grunspan20* and Aaron D Goldberg, MD, PhD21

1Rabin Medical Center, Petah Tikva, Israel
2Dana-Farber Cancer Institute, Boston, MA
3Weill Cornell Medicine, New York, NY
4O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL
5Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC
6Medical College of Wisconsin, Milwaukee, WI
7Moffitt Cancer Center, Tampa, FL
8University of Pennsylvania Perelman Center for Advanced Medicine, Philadelphia, PA
9Tel Aviv (Sourasky) Medical Center, Tel Aviv, Israel
10University of Colorado School of Medicine, Aurora, CO
11Scripps-MD Anderson, San Diego, CA
12Hadassah-Hebrew University Medical Centre, Jerusalem, Israel
13Rambam Health Care Campus, Haifa, Israel
14Janssen Research and Development, New Brunswick, NJ
15AbbVie Inc, North Chicago, IL
16AbbVie, Inc., North Chicago, IL
17AbbVie Inc., North Chicago, IL
18Analysis Group Inc, Montreal, Canada
19Genentech, South San Francisco, CA
20AbbVie Inc., Hod-Hasharon, Israel
21Memorial Sloan Kettering Cancer Center, New York, NY

Introduction: Venetoclax (VEN; a BCL-2 inhibitor) is approved in combination with hypomethylating agents (HMA) or low dose cytarabine for ND adults with AML ineligible for intensive chemotherapy (IC) (i.e., ≥75 years old or comorbidities that preclude use of IC). This study describes the real-world characteristics and clinical outcomes of patients (pts) treated with VEN-HMA vs. non-VEN-based regimens in the ARC Initiative, overall and specifically among pts ≥75 years old or with comorbidities.

Methods: A multicenter chart review study including randomly selected adult pts with ND AML treated with VEN (VEN cohort) after April 2016 from 14 academic sites (US: 10; Israel: 4) matched 1:1 to control pts who received non-VEN-based regimens after May 2015 (CON cohort) based on age (<60, 60-74, ≥75) and ELN risk. Interim descriptive results from May 2022 are presented; data collection is ongoing. Clinical outcomes, including composite complete remission (CRc; i.e., CR, CRh, or CRi), minimal residual disease (MRD; assessed by flow cytometry or molecular monitoring), overall survival (OS), hematopoietic cell transplantation (HCT), and transfusion independence (TI), were compared between the VEN cohort and matched CON cohort. A subset of VEN pts ≥75 years old or with ≥1 comorbidity of interest (based on the Ferrara criteria) and their matched CON pts were analyzed separately (unfit subgroup) and results among pts with TP53 and IDH1/2 mutation were also reported.

Results: Results are described in Table 1. A total of 176 VEN pts and 176 CON pts were included, including 116 unfit VEN with their matched CON pts. Overall, VEN pts received VEN-azacitidine (AZA; 76.1%) or VEN-decitabine (DEC; 23.9%) and 65.3% of CON pts received high intensity regimens. In the unfit subgroup, VEN pts received VEN-AZA (77.6%) or VEN-DEC (22.4%) and 55.2% of CON pts received high intensity regimens. The proportion of pts who were ≥75 years old was 34.1% and 50.9% in the unfit subgroup. A total of 64.8% of all pts were classified as ELN adverse risk, which was 67.2% in the unfit subgroup. Among pts with genetic mutations tested, 22.2% of VEN pts and 13.5% of CON pts had TP53 mutations and 19.9% and 14.6% had IDH1/2 mutations, respectively, which was similar in the unfit subgroup of each cohort.

Among pts with a response assessment, 65.7% of VEN pts and 53.5% of CON pts achieved CRc (p<0.05) and 39.6% of VEN pts and 43.4% of CON pts achieved CR (p=0.53). In the unfit subgroup with a response assessment, 66.1% of pts in the VEN cohort and 44.6% of pts in the CON cohort achieved CRc (p<0.01) and 37.5% of VEN pts and 36.0% of CON pts achieved CR (p=0.91). Among pts with TP53 mutations, response was not statistically different for the overall and unfit subgroup. Among pts with IDH1/2 mutations, CRc was significantly higher in overall VEN versus CON (87.9% vs. 54.2%; p<0.01) and in the unfit subgroup (85.7% vs. 52.9%; p<0.05). The duration of CRc was not statistically different between the VEN and CON cohorts, overall or in the unfit subgroup.

For pts who achieved CRc and had MRD assessed, 74.0% of VEN pts and 66.7% of CON pts had negative MRD. Similar proportions were observed overall and for IDH1/2 in the unfit subgroup although statistical significance was not met.

HCT rate was 6.8% and 14.2% in the VEN and CON cohorts (p<0.05) and 6.9% and 12.1% in the unfit subgroup, respectively (p=0.26). The median OS was 15.8 and 13.9 months in the VEN and CON cohorts, respectively (p=0.20) and 17.1 and 12.4 months in the unfit subgroup (p=0.30). The 6-month OS rate was 74.3% and 70.1% in the VEN and CON cohorts (p=0.30) and 75.6% and 66.2% in the unfit subgroup (p=0.10). Among the pts with ≥56 days of follow-up, 61.9% and 54.8% in the VEN and CON cohorts (p=0.29) and 67.0% and 51.1% in the unfit subgroup (p=0.05), respectively, achieved TI.

Conclusions: Pts with ND AML receiving VEN-HMA had significantly higher rates of CRc than matched pts on non-VEN-based regimens in the overall population, those unfit for IC, and with IDH1/2 mutations. OS and durability of response were similar in VEN and CON pts, despite 65% of pts in the overall CON cohort receiving IC and 55% in the unfit subgroup. VEN pts who were considered as unfit had similar clinical outcomes to the overall VEN pts. Although VEN pts with TP53 mutation had non-significantly higher CRc rates compared with CON pts, median OS was poor in both groups highlighting the need for novel approaches in this high-risk molecular subset.

Disclosures: Wolach: Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Neopharm: 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; Jansen: 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; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Garcia: AbbVie: Research Funding; AbbVie, Astellas, and Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Advisory Board ; AbbVie, Genentech, AstraZeneca, Prelude and Pfizer: Other: Clinical trial support (institutional) , Research Funding. Desai: Janssen Research: Research Funding; Takeda, Bristol Myers Squibb, Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees. Vachhani: Incyte: Speakers Bureau; Blueprint Medicines, Incyte, AbbVie, CTI BioPharma Corp, Novartis, Amgen, Pfizer, Genentech, Stemline: Consultancy. Zeidner: Sumitomo Dainippon Pharma: Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Stemline: Research Funding; Merck: Research Funding; Jazz: Research Funding; Astex: Research Funding; Arog: Research Funding; Shattuck Labs: Honoraria; Servier: Consultancy, Honoraria; Immunogen: Honoraria; Gilead: Consultancy, Honoraria, Research Funding; Genentech: Honoraria; Bristol Myers Squibb: Honoraria; Takeda: Research Funding; Syndax: Research Funding. Abedin: AltruBio Inc.: Research Funding; Helsinn Healthcare: Research Funding; Pfizer: Research Funding; Actinium Pharmaceuticals: Research Funding; Incyte: Research Funding; Stemline: Honoraria; Amgen: Honoraria; AbbVie: Honoraria; Daichi Sankyo: Honoraria; Servier: Honoraria. Sweet: Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead Sciences, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Mablytics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AROG: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Research Funding; Syntrix Pharmaceuticals: Research Funding; berGenBio: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Curis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Lai: Astellas, Jazz: Speakers Bureau; AbbVie, Agios/Servier, Daiichi-Sankyo, Jazz, Macrogenics, PDS, Pfizer, Genentech, Taiho, Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees. Moshe: Abbvie: Consultancy, Honoraria, 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; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: lectures. Xavier: Janssen, Pharmacyclics Kite, Gilead, Genentech, AstraZeneca, Verastem: Honoraria; AbbVie, Acrotec, Genentech, Chugai: Consultancy; Biegene, Morphosys, Incyte, AbbVie, Seattle Genetics, AstraZeneca, Celgene, BMS, Epizyme, ADC Therapeutics, TG Therapeutics, Blueprint Medicines, Loxo/Lilly, Pharmacyclics: Speakers Bureau. Nachmias: AbbVie, BMS: Membership on an entity's Board of Directors or advisory committees, Other: lectures. Zuckerman: Orgenesis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BioSight Ltd: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Cellect Biotechnology: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau. Lee: BMS, Innate, Pin Therapeutics: Consultancy; Janssen Research and Development: Current Employment; AbbVie: Consultancy. Bui: AbbVie: Current Employment, Current equity holder in private company, Current holder of stock options in a privately-held company. Cheng: AbbVie: Current Employment, Current equity holder in private company, Current holder of stock options in a privately-held company. Miller: AbbVie: Current Employment, Current equity holder in publicly-traded company. Guerin: 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, Current equity holder in publicly-traded company. Montez: Genentech/Roche: Current Employment, Current equity holder in publicly-traded company; Roche: Current equity holder in publicly-traded company. Grunspan: AbbVie: Current Employment, Current equity holder in private company, Current holder of stock options in a privately-held company. Goldberg: Genentech: Consultancy; Aprea, Aptose, AROG, Celularity, Pfizer, Prelude Therapeutics: Research Funding; Moderna, Novavax: Current equity holder in publicly-traded company; DAVA Oncology: Honoraria; Astellas: 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, Research Funding.

*signifies non-member of ASH