Prognostic value of measurable residual disease after venetoclax and decitabine in acute myeloid leukemia
Abhishek Maiti, Courtney D. DiNardo, Sa A. Wang, Jeffrey L. Jorgensen, Tapan M. Kadia, Naval Daver, Nicholas J. Short, Musa Yılmaz, Naveen Pemmaraju, Gautam Borthakur, Prithviraj Bose, Ghayas C. Issa, Alessandra Ferrajoli, Elias Jabbour, Nitin Jain, Guillermo Garcia‐Manero, Maro Ohanian, Koichi Takahashi, Guillermo Montalban‐Bravo, Lucia Masárová, Jan A. Burger, Philip A. Thompson, Srđan Verstovšek, Koji Sasaki, Michael Andreeff, Caitlin R. Rausch, Kathryn Montalbano, Sherry Pierce, Wei Qiao, Jing Ning, Hagop M. Kantarjian, Marina Konopleva, Farhad Ravandi
Abstract
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.