Dataset Information

Measurable Residual Disease Response and Prognosis in Treatment-Naive Acute Myeloid Leukemia With Venetoclax and Azacitidine.

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.

SUBMITTER: Pratz KW

PROVIDER: S-EPMC8906463 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Publications

Measurable Residual Disease Response and Prognosis in Treatment-Naïve Acute Myeloid Leukemia With Venetoclax and Azacitidine.

Pratz Keith W KW Jonas Brian A BA Pullarkat Vinod V Recher Christian C Schuh Andre C AC Thirman Michael J MJ Garcia Jacqueline S JS DiNardo Courtney D CD Vorobyev Vladimir V Fracchiolla Nicola S NS Yeh Su-Peng SP Jang Jun Ho JH Ozcan Muhit M Yamamoto Kazuhito K Illes Arpad A Zhou Ying Y Dail Monique M Chyla Brenda B Potluri Jalaja J Döhner Hartmut H

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20211215 8

<h4>Purpose</h4>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<sup>-3</sup> in the VIALE-A trial.<h4>Methods</h4>The patients included in this repo ...[more]

PMID: 34910556

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Project description:Assessment of measurable residual disease (MRD) provides prognostic information in acute myeloid leukemia (AML). However, the utility of MRD with venetoclax-based lower intensity regimens is unknown. We analyzed the prognostic value of achieving a negative MRD in older/"unfit" patients with AML receiving first-line therapy with 10-day decitabine and venetoclax. MRD was evaluated in bone marrow specimens using multicolor flow cytometry (sensitivity 0.1%). Ninety-seven patients achieving either a complete remission (CR) or CR with incomplete hematologic recovery (CRi) or morphologic leukemia-free state were included. Median age was 72 years (interquartile range, 68-78 years), and 64% had adverse-risk AML. Eighty-three patients achieved CR/CRi, and 52 (54%) became MRD negative. Median time to becoming MRD negative was 2.0 months (interquartile range, 0.9-3.1 months). Patients becoming MRD negative by 2 months had longer relapse-free survival (RFS) compared with those remaining MRD positive (median RFS, not reached vs 5.2 months; hazard ratio [HR], 0.31; 95% confidence interval [CI], 0.12-0.78; P = .004), longer event-free survival (EFS) (median EFS, not reached vs 5.8 months; HR, 0.25; 95% CI, 0.12-0.55; P < .001), as well as longer overall survival (OS) (median OS, 25.1 vs 7.1 months; HR, 0.23; 95% CI, 0.11-0.51; P < .001). Patients achieving an MRD-negative CR had longer OS compared with those with an inferior response (median OS, 25.1 vs 11.6 months; HR, 0.33; 95% CI, 0.19-0.58; P < .0005). Patients becoming MRD negative within 1 month had an improved OS compared with MRD-positive patients (median OS, 25.1 vs 3.4 months; HR, 0.15; 95% CI, 0.03-0.64; P < .0001). Differential impact of MRD status on survival outcomes persisted at a later 4-month time point of evaluation. In conclusion, MRD-negative status at 1, 2, and 4 months after starting therapy confers significantly better survival in older/unfit patients with AML receiving first-line therapy with 10-day decitabine and venetoclax. This trial was registered at www.clinicaltrials.gov as #NCT03404193.

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