TY - JOUR
T1 - Prognostic value of measurable residual disease after venetoclax and decitabine in acute myeloid leukemia
AU - Maiti, Abhishek
AU - DiNardo, Courtney D.
AU - Wang, Sa A.
AU - Jorgensen, Jeffrey
AU - Kadia, Tapan M.
AU - Daver, Naval G.
AU - Short, Nicholas J.
AU - Yilmaz, Musa
AU - Pemmaraju, Naveen
AU - Borthakur, Gautam
AU - Bose, Prithviraj
AU - Issa, Ghayas C.
AU - Ferrajoli, Alessandra
AU - Jabbour, Elias J.
AU - Jain, Nitin
AU - Garcia-Manero, Guillermo
AU - Ohanian, Maro
AU - Takahashi, Koichi
AU - Montalban-Bravo, Guillermo
AU - Masarova, Lucia
AU - Burger, Jan A.
AU - Thompson, Philip A.
AU - Verstovsek, Srdan
AU - Sasaki, Koji
AU - Andreeff, Michael
AU - Rausch, Caitlin R.
AU - Montalbano, Kathryn S.
AU - Pierce, Sherry
AU - Qiao, Wei
AU - Ning, Jing
AU - Kantarjian, Hagop M.
AU - Konopleva, Marina Y.
AU - Ravandi, Farhad
N1 - Publisher Copyright:
© 2021 by The American Society of Hematology.
PY - 2021
Y1 - 2021
N2 - 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 5 .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.
AB - 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 5 .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.
UR - http://www.scopus.com/inward/record.url?scp=85104500293&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85104500293&partnerID=8YFLogxK
U2 - 10.1182/BLOODADVANCES.2020003717
DO - 10.1182/BLOODADVANCES.2020003717
M3 - Article
C2 - 33792630
AN - SCOPUS:85104500293
SN - 2473-9529
VL - 5
SP - 1876
EP - 1883
JO - Blood Advances
JF - Blood Advances
IS - 7
ER -