Keith W Pratz1, Brian A Jonas2, Vinod Pullarkat3, Christian Recher4, Andre C Schuh5, Michael J Thirman6, Jacqueline S Garcia7, Courtney D DiNardo8, Vladimir Vorobyev9, Nicola S Fracchiolla10, Su-Peng Yeh11, Jun Ho Jang12, Muhit Ozcan13, Kazuhito Yamamoto14, Arpad Illes15, Ying Zhou16, Monique Dail17, Brenda Chyla16, Jalaja Potluri16, Hartmut Döhner18. 1. Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA. 2. Department of Internal Medicine, Division of Hematology and Oncology, University of California Davis School of Medicine, Sacramento, CA. 3. Department of Hematology and Hematopoietic Cell Transplantation and Gehr Family Center for Leukemia Research, City of Hope Comprehensive Cancer Center, Duarte, CA. 4. Centre Hospitalier Universitaire de Toulouse, Institut Universitaire du Cancer de Toulouse Oncopole, Université de Toulouse 3 Paul Sabatier, Toulouse, France. 5. Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada. 6. Section of Hematology/Oncology, Department of Medicine, The University of Chicago Medicine, Chicago, IL. 7. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA. 8. Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX. 9. Department of Hematology, S. P. Botkin City Clinical Hospital, Moscow, Russia. 10. UOC Ematologia, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy. 11. Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan. 12. Department of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. 13. Department of Hematology, Ankara University School of Medicine, Ankara, Turkey. 14. Department of Hematology and Cell Therapy, Aichi Cancer Center Hospital, Nagoya, Japan. 15. University of Debrecen, Faculty of Medicine, Department of Hematology, Debrecen, Hungary. 16. AbbVie Inc., North Chicago, IL. 17. Genentech Inc., South San Francisco, CA. 18. Department of Internal Medicine III, Ulm University Hospital, Ulm, Germany.
Abstract
PURPOSE: There is limited evidence on the clinical utility of monitoring measurable residual disease (MRD) in patients with acute myeloid leukemia treated with lower-intensity therapy. Herein, we explored the outcomes of patients treated with venetoclax and azacitidine who achieved composite complete remission (CRc; complete remission + complete remission with incomplete hematologic recovery) and MRD < 10-3 in the VIALE-A trial. METHODS: The patients included in this report were treated with venetoclax and azacitidine. Bone marrow aspirate samples for multiparametric flow cytometry assessments were collected for central analysis at baseline, end of cycle 1, and every three cycles thereafter. MRD-negative response was defined as < 1 residual blast per 1,000 leukocytes (< 10-3 or 0.1%) with an estimated analytic sensitivity of 0.0037%-0.0027%. CRc, duration of remission (DoR), event-free survival (EFS), and overall survival (OS) were assessed. A multivariate Cox regression analysis identified prognostic factors associated with OS. RESULTS: One hundred sixty-four of one hundred ninety (86%) patients with CRc were evaluable for MRD. MRD < 10-3 was achieved by 67 of 164 (41%), and 97 of 164 (59%) had MRD ≥ 10-3. The median DoR, EFS, and OS were not reached in patients with CRc and MRD < 10-3, and the 12-month estimates for DoR, EFS, and OS in this group were 81.2%, 83.2%, and 94.0%. Among patients with CRc and MRD ≥ 10-3, the median DoR, EFS, and OS were 9.7, 10.6, and 18.7 months. Multivariate analysis showed that CRc with MRD < 10-3 was a strong predictor of OS (adjusted hazard ratio = 0.285; 95% CI, 0.159 to 0.510; P < .001). CONCLUSION: Patients who achieved CRc and MRD < 10-3 with venetoclax and azacitidine had longer DoR, EFS, and OS, than responding patients with MRD ≥ 10-3.
PURPOSE: There is limited evidence on the clinical utility of monitoring measurable residual disease (MRD) in patients with acute myeloid leukemia treated with lower-intensity therapy. Herein, we explored the outcomes of patients treated with venetoclax and azacitidine who achieved composite complete remission (CRc; complete remission + complete remission with incomplete hematologic recovery) and MRD < 10-3 in the VIALE-A trial. METHODS: The patients included in this report were treated with venetoclax and azacitidine. Bone marrow aspirate samples for multiparametric flow cytometry assessments were collected for central analysis at baseline, end of cycle 1, and every three cycles thereafter. MRD-negative response was defined as < 1 residual blast per 1,000 leukocytes (< 10-3 or 0.1%) with an estimated analytic sensitivity of 0.0037%-0.0027%. CRc, duration of remission (DoR), event-free survival (EFS), and overall survival (OS) were assessed. A multivariate Cox regression analysis identified prognostic factors associated with OS. RESULTS: One hundred sixty-four of one hundred ninety (86%) patients with CRc were evaluable for MRD. MRD < 10-3 was achieved by 67 of 164 (41%), and 97 of 164 (59%) had MRD ≥ 10-3. The median DoR, EFS, and OS were not reached in patients with CRc and MRD < 10-3, and the 12-month estimates for DoR, EFS, and OS in this group were 81.2%, 83.2%, and 94.0%. Among patients with CRc and MRD ≥ 10-3, the median DoR, EFS, and OS were 9.7, 10.6, and 18.7 months. Multivariate analysis showed that CRc with MRD < 10-3 was a strong predictor of OS (adjusted hazard ratio = 0.285; 95% CI, 0.159 to 0.510; P < .001). CONCLUSION: Patients who achieved CRc and MRD < 10-3 with venetoclax and azacitidine had longer DoR, EFS, and OS, than responding patients with MRD ≥ 10-3.
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