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2328 Comparative Effectiveness of Venetoclax Combinations Vs Other Therapies Among Patients with Newly Diagnosed Acute Myeloid Leukemia: Results from the AML Real World Evidence (ARC) Initiative

Program: Oral and Poster Abstracts
Session: 615. Acute Myeloid Leukemias: Commercially Available Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster II
Hematology Disease Topics & Pathways:
AML, Clinical Research, Diseases, Real World Evidence, Myeloid Malignancies
Sunday, December 12, 2021, 6:00 PM-8:00 PM

Jacqueline S. Garcia, MD1, Ofir Wolach2*, Pankit Vachhani3*, Joshua F. Zeidner, MD4, Chetasi Talati, MD5*, Daniel A. Pollyea, MD6, Catherine Lai, MD, MPH7, Yakir Moshe, MD, PhD8*, Sameem Abedin, MD9, David Lavie10*, Tsila Zuckerman, MD11, Marin Xavier12*, Sangmin Lee, MD13, Wesleigh Edwards12, Evan Chen1*, Cat N. Bui14*, Anders Svensson, MD14*, Rebecca Burne15*, Steve Kye14, Jessica Maitland15*, Esprit Ma16*, Melissa Montez16*, Moshe Grunspan17* and Aaron D Goldberg, MD, PhD18

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

Introduction: Venetoclax (VEN) is a BCL-2 inhibitor FDA approved in combination with azacitidine (AZA), decitabine (DEC), or low-dose cytarabine (LDAC) for newly diagnosed (ND) acute myeloid leukemia (AML) in adults aged ≥75 or those with comorbidities precluding intensive chemotherapy. We explored real-world practices and clinical outcomes of patients (pts) treated with VEN-based vs. non-VEN-based regimens in the AML Real world evidenCe (ARC) Initiative.

Methods: This multicenter chart review study includes adult pts with ND AML treated with VEN (VEN cohort) after 11 April 2016 matched to pts with non-VEN-based regimens (control cohort) after 15 May 2015 from 10 academic sites in the US and 4 in Israel. Pts were randomly selected and matched on age (<60; 60-74; ≥75) and ELN risk. Interim descriptive results (data cut: 17 May 2021) are presented; data collection is ongoing with a targeted sample of ≥500 matched pts. Response to therapy, as reported by physicians in the patient chart, hematopoietic cell transplantation (HCT) rate, and Kaplan-Meier (KM) estimates of overall survival (OS), event-free survival (EFS), and duration of response (DOR) were analyzed. Subgroups of pts aged <75 and with adverse ELN risk were analyzed separately.

Results: Select results are shown in Table 1. 133 VEN and 133 control ND AML pts were included. Median age was 73 years (Range: 34-89) in the VEN cohort and 71 years (Range: 40-89) in the control cohort; 60.9% of matched pts were <75 (<75 subgroup; 81 VEN and 81 control). In both cohorts, 64.7% of pts had adverse ELN risk. VEN pts received VEN+AZA (106 pts, 79.7%), VEN+DEC (24 pts, 18.0%), or VEN+LDAC (3 pts, 2.3%). In the control cohort, 37.6% of pts received low-intensity regimens (largely DEC [19.5%] and AZA [14.3%]) and 62.4% received high-intensity regimens (e.g., cytarabine+daunorubicin [27.1%] and CPX-351 [15.8%]), with a higher proportion of pts on high-intensity regimens in the <75 subgroup (85.2%) and a lower proportion in the adverse-risk subgroup (54.7%). IDH1/IDH2 mutations were present in 16.5% and 15.8% of pts in the VEN and control cohorts, respectively, and NPM1 mutations were present in 11.4% and 11.8% of pts. Across subgroups, TP53 mutation was present in higher proportions of VEN pts compared to control.

The mean duration of follow-up was 9.2 months in the VEN cohort and 14.6 months in the control cohort and the mean duration of treatment was 6.9 months and 4.3 months. Composite complete remission (CCR: CR+CRi) rate was 60.4% in the VEN cohort and 50.0% in the control cohort and rate of MLFS was 7.2% and 3.4%, respectively; among the pts who achieved a response (CR, CRi, CRh, or MLFS; 81 VEN and 68 control pts), median time to best response was 1.7 months and 1.3 months, respectively. The 1-year KM DOR for patients who achieved CCR was 57.7% in the VEN cohort and 53.1% in the control cohort. After initial therapy, 5.3% of pts in the VEN cohort and 15.0% of pts in the control cohort were referred to HCT. The 1-year KM OS was 62.6% in the VEN cohort and 49.8% in the control cohort and the 1-year KM EFS was 41.4% and 31.5%.

In the <75 subgroup (81 VEN and 81 control pts), outcomes were similar between cohorts, despite a higher proportion of pts with comorbidities in the VEN cohort (87.7%) than the control cohort (77.8%); rates of CCR were 61.2% in the VEN cohort and 57.1% in the control cohort; after initial chosen therapy, 7.4% and 22.2% of pts were referred to HCT in the VEN and control cohort, respectively. The 1-year KM OS was 55.4% in the VEN cohort and 55.5% in the control cohort, and the 1-year KM EFS was 38.4% and 38.1%. In the adverse-risk subgroup, rates of CCR were 50.7% in the VEN cohort and 37.8% in the control cohort; after initial chosen therapy, 4.7% and 10.5% of pts were referred to HCT in the VEN and control cohort, respectively. The 1-year KM OS was 51.1% in the VEN cohort and 39.8% in the control cohort and the 1-year KM EFS was 28.4% and 27.2%.

Conclusions: The current analyses support real-world treatment effectiveness of VEN combinations and are consistent with data reported from clinical trials, despite the relatively short follow-up at the time of interim analyses. The outcomes, including OS at 1 year, for VEN combinations in ND AML pts appear similar to matched control pts, including the subgroup of pts <75 who largely received high-intensity regimens, and a lower proportion had comorbidities. Further analyses of matched pts are ongoing.


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

*signifies non-member of ASH