MEASURABLE RESIDUAL DISEASE RESPONSE IN ACUTE MYELOID LEUKEMIA TREATED WITH VENETOCLAX AND AZACITIDINE
Author(s): ,
Keith W. Pratz
Affiliations:
Abramson Cancer Center, University of Pennsylvania,Philadelphia,United States
,
Brian A. Jonas
Affiliations:
Department of Internal Medicine, Division of Hematology and Oncology, University of California Davis School of Medicine,Sacramento,United States
,
Vinod Pullarkat
Affiliations:
Department of Hematology and Hematopoietic Cell Transplantation and Gehr Family Center for Leukemia Research, City of Hope Comprehensive Cancer Center,Duarte,United States
,
Christian Recher
Affiliations:
Centre Hospitalier Universitaire de Toulouse,Toulouse,France
,
Andre C. Schuh
Affiliations:
Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre,Toronto,Canada
,
Michael J. Thirman
Affiliations:
Section of Hematology/Oncology, Department of Medicine, The University of Chicago Medicine,Chicago,United States
,
Jacqueline S. Garcia
Affiliations:
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School,Boston,United States
,
Courtney DiNardo
Affiliations:
Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center,Houston,United States
,
Vladimir Vorobyev
Affiliations:
Department of Hematology, S. P. Botkin City Clinical Hospital,Moscow,Russian Federation
,
Nicola Fracchiolla
Affiliations:
UOC Ematologia, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico,Milan,Italy
,
Su-Peng Yeh
Affiliations:
Department of Internal Medicine, China Medical University Hospital,Taichung,Taiwan, Province of China
,
Jun Ho Jang
Affiliations:
Department of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine,Seoul,Korea, Republic Of
,
Muhit Ozcan
Affiliations:
Department of Hematology, Ankara University School of Medicine,Ankara,Turkey
,
Kazuhito Yamamoto
Affiliations:
Department of Hematology and Cell Therapy, Aichi Cancer Center Hospital,Nagoya,Japan
,
Arpad Illes
Affiliations:
University of Debrecen, Faculty of Medicine, Department of Hematology,Debrecen,Hungary
,
Ying Zhou
Affiliations:
AbbVie Inc.,North Chicago,United States
,
Monique Dail
Affiliations:
Genentech Inc.,South San Francisco,United States
,
Brenda Chyla
Affiliations:
AbbVie Inc.,North Chicago,United States
,
Jalaja Potluri
Affiliations:
AbbVie Inc.,North Chicago,United States
Hartmut Döhner
Affiliations:
Department of Internal Medicine III, University Hospital,Ulm,Germany
EHA Library. W. Pratz K. 06/09/21; 324545; S137
Keith W. Pratz
Keith W. Pratz
Contributions
Abstract
Presentation during EHA2021: All Oral presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: S137

Type: Oral Presentation

Session title: Developments in AML therapy

Background
In the phase 3 VIALE-A trial, rates of composite complete remission (CRc; complete remission [CR] + CR with incomplete hematologic recovery [CRi]) and measurable residual disease response (MRD<10-3) were higher in patients (pts) treated with venetoclax (Ven) + azacitidine (Aza) compared to Aza alone (23.4%/7.6%, p<0.001). There is limited evidence of the clinical significance of MRD monitoring in pts receiving low-intensity chemotherapy. 

Aims
We explored the outcomes of pts treated with Ven+Aza who achieved both CRc and MRD<10-3 in the VIALE-A trial (NCT02993523).

Methods
Enrolled pts were18 years and unfit for intensive chemotherapy. Pts received Ven 400 mg orally; days 1–28 and Aza 75 mg/m2; days 1-7/28-day cycle. Bone marrow aspirate samples for multiparametric flow cytometry assessments by integrated leukemia-associated immunophenotypes and different than normal procedures were collected for central analysis (Covance Central Laboratory Services) at baseline, end of cycle 1, and every 3 cycles thereafter. Assessments were performed independent of disease responses. MRD response was defined as <1 residual blast /1000 leukocytes (<10-3). CRc, DoR, OS, and EFS were assessed. Disease assessments were per modified International Working Group response criteria for AML.

Results
211/286 (74%) pts treated with Ven+Aza with at least one valid post-baseline MRD assessment were considered MRD evaluable; 78/211 (37%) achieved MRD<10-3 and 133/211 (63%) had MRD10-3. Median age (MRD<10-3/ MRD10-3) was 76 (range: 49-89)/77 (58-91) years.

Pts (MRD<10-3/ MRD10-3) received median of 14.5 (range: 1-28) /7.0 (1-30) cycles of Ven+Aza. At a median follow-up of 22.0 (range: 20.1-23.0)/20.8 (19.8-22.3) months (mos), CRc + MRD<10-3/ MRD10-3 was achieved by 67 (86%)/ 97 (73%); 20/67 (30%) achieved CRc + MRD<10-3 by end of cycle 1.


Median DoR, OS, and EFS were not reached in pts with CRc + MRD<10-3 response (Table). The 12-mo estimates for DoR, OS, and EFS for pts with CRc + MRD<10-3response were 81.2%, 94.0%, and 83.2%, respectively. Adverse events grade 3 (MRD<10-3/ MRD10-3) were febrile neutropenia (50%/43%), neutropenia (50%/35%), and thrombocytopenia (44%/44%), similar to the overall population.

Conclusion
Pts with best response of CRc who achieved MRD<10-3response with Ven+Aza treatment had longer DoR, OS, and EFS than pts who were CRc and MRD positive.

Keyword(s): Acute myeloid leukemia, Clinical trial, MRD

Presentation during EHA2021: All Oral presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: S137

Type: Oral Presentation

Session title: Developments in AML therapy

Background
In the phase 3 VIALE-A trial, rates of composite complete remission (CRc; complete remission [CR] + CR with incomplete hematologic recovery [CRi]) and measurable residual disease response (MRD<10-3) were higher in patients (pts) treated with venetoclax (Ven) + azacitidine (Aza) compared to Aza alone (23.4%/7.6%, p<0.001). There is limited evidence of the clinical significance of MRD monitoring in pts receiving low-intensity chemotherapy. 

Aims
We explored the outcomes of pts treated with Ven+Aza who achieved both CRc and MRD<10-3 in the VIALE-A trial (NCT02993523).

Methods
Enrolled pts were18 years and unfit for intensive chemotherapy. Pts received Ven 400 mg orally; days 1–28 and Aza 75 mg/m2; days 1-7/28-day cycle. Bone marrow aspirate samples for multiparametric flow cytometry assessments by integrated leukemia-associated immunophenotypes and different than normal procedures were collected for central analysis (Covance Central Laboratory Services) at baseline, end of cycle 1, and every 3 cycles thereafter. Assessments were performed independent of disease responses. MRD response was defined as <1 residual blast /1000 leukocytes (<10-3). CRc, DoR, OS, and EFS were assessed. Disease assessments were per modified International Working Group response criteria for AML.

Results
211/286 (74%) pts treated with Ven+Aza with at least one valid post-baseline MRD assessment were considered MRD evaluable; 78/211 (37%) achieved MRD<10-3 and 133/211 (63%) had MRD10-3. Median age (MRD<10-3/ MRD10-3) was 76 (range: 49-89)/77 (58-91) years.

Pts (MRD<10-3/ MRD10-3) received median of 14.5 (range: 1-28) /7.0 (1-30) cycles of Ven+Aza. At a median follow-up of 22.0 (range: 20.1-23.0)/20.8 (19.8-22.3) months (mos), CRc + MRD<10-3/ MRD10-3 was achieved by 67 (86%)/ 97 (73%); 20/67 (30%) achieved CRc + MRD<10-3 by end of cycle 1.


Median DoR, OS, and EFS were not reached in pts with CRc + MRD<10-3 response (Table). The 12-mo estimates for DoR, OS, and EFS for pts with CRc + MRD<10-3response were 81.2%, 94.0%, and 83.2%, respectively. Adverse events grade 3 (MRD<10-3/ MRD10-3) were febrile neutropenia (50%/43%), neutropenia (50%/35%), and thrombocytopenia (44%/44%), similar to the overall population.

Conclusion
Pts with best response of CRc who achieved MRD<10-3response with Ven+Aza treatment had longer DoR, OS, and EFS than pts who were CRc and MRD positive.

Keyword(s): Acute myeloid leukemia, Clinical trial, MRD

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