DURABLE RESPONSE WITH VENETOCLAX IN COMBINATION WITH DECITABINE OR AZACITADINE IN ELDERLY PATIENTS WITH ACUTE MYELOID LEUKEMIA (AML)
Author(s): ,
Courtney D. DiNardo
Affiliations:
Department of Leukemia, The University of Texas MD Anderson Cancer Center,Houston,United States
,
Keith Pratz
Affiliations:
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University,Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University,United States
,
Jalaja Potluri
Affiliations:
AbbVie, Inc.,North Chicago,United States
,
Vinod Pullarkat
Affiliations:
Department of Hematology and Hematopoietic Cell Transplantation and Gehr Family Center for Leukemia Research, City of Hope National Medical Center,Duarte,United States
,
Brian A. Jonas
Affiliations:
University of California Davis Comprehensive Cancer Center,Sacramento,United States
,
Andrew H. Wei
Affiliations:
The Alfred Hospital and Monash University,Melbourne,United States
,
Pamela S. Becker
Affiliations:
Clinical Research Division, Fred Hutchinson Cancer Research Center and Division of Hematology, Department of Medicine, University of Washington School of Medicine,Seattle,United States
,
Olga Frankfurt
Affiliations:
Northwestern University Feinberg School of Medicine,Chicago,United States
,
Tu Xu
Affiliations:
AbbVie, Inc.,North Chicago,United States
,
Wan-Jen Hong
Affiliations:
Genentech, Inc.,South San Francisco,United States
,
Brenda Chyla
Affiliations:
AbbVie, Inc.,North Chicago,United States
,
Daniel A. Pollyea
Affiliations:
University of Colorado School of Medicine,Aurora,United States
Anthony Letai
Affiliations:
Department of Medical Oncology, Dana-Farber Cancer Institute,Boston,United States
EHA Learning Center. D. DiNardo C. Jun 17, 2018; 214482
Courtney D. DiNardo
Courtney D. DiNardo

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Abstract
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Abstract: S1563

Type: Oral Presentation

Presentation during EHA23: On Sunday, June 17, 2018 from 08:45 - 09:00

Location: Victoria Hall

Background
Venetoclax (VEN), an oral BCL-2 inhibitor, has synergistic activity when combined with hypomethylating agents. 

Aims
This clinical study explores the optimal dose and efficacy of VEN in combination with decitabine (DEC) or azacitadine (AZA) in elderly AML.

Methods
This is an open-label, phase 1b, dose escalation and expansion study (NCT02203773) on the safety and efficacy of VEN, with DEC or AZA, in elderly patients (≥65 years) with untreated AML. VEN was coadministered daily with 20 mg/m2 of DEC on days 1-5 or 75 mg/m2 of AZA on days 1-7, each 28 day cycle. VEN was dosed at 400, 800, or 1200 mg in the escalation phase, and 400 or 800 mg in the expansion phase. Complete remission (CR), CR with incomplete blood count recovery (CRi), overall survival (OS) and adverse events (AEs) were evaluated.

Results
Data cutoff was July 7, 2017. Of 145 patients, 56% were male; the median age was 74 years (range: 65–86). Overall, 60, 74, and 11 patients received VEN at 400, 800, and 1200 mg, respectively. Key grade ≥3 AEs were febrile neutropenia (43%), thrombocytopenia (23%) and neutropenia (16%); pneumonia and bacteremia (all grades) occurred in 18% and 8% of patients, respectively. At 400mg of VEN, the rate of CR+CRi was 73% (76% with AZA and 71% with DEC); efficacy data are in the table. Minimal residual disease (MRD) assessment in marrow aspirates was performed at disease assessment in a central lab using multicolor flow cytometry assay; overall, 37% (36/97) of patients with CR/CRi had MRD levels below the 10-3 cutoff. Median follow up was 15.1 months.

 

 

CR/CRi

Duration of CR/CRi

OS

Patient subgroup

n

n (%)

median months

All VEN doses

145

97 (67)

11.3

17.5

      Intermediate cytogenetic risk

74

55 (74)

12.9

NR

      Poor cytogenetic risk

71

42 (59)

6.7

9.6

      Secondary AML

36

24 (67)

NR

NR

      Age ≥75 years

62

40 (65)

9.2

11.0

VEN 400 mg

 

 

 

 

      + AZA

29

22 (76)

NR

NR

      + DEC

31

22 (71)

12.5

15.2

VEN 800 mg

 

 

 

 

      + AZA

37

21 (57)

11.7

14.2

      + DEC

37

27 (73)

9.2

17.5

OS, overall survival; NR, not yet reached (if applicable)

Conclusion

Preliminary data suggest that 400 mg of VEN has the optimal benefit-risk profile in combination with DEC or AZA, which demonstrated a tolerable safety profile with deep responses and durable outcomes in elderly patients with AML.

Session topic: 4. Acute myeloid leukemia - Clinical

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