Ten-day decitabine with venetoclax versus intensive chemotherapy in relapsed or refractory acute myeloid leukemia: A propensity score-matched analysis.

BACKGROUND: Relapsed/refractory (R/R) acute myeloid leukemia (AML) has poor outcomes. Although lower-intensity venetoclax-containing regimens are standard for older/unfit patients with newly diagnosed AML, it is unknown how such regimens compare with intensive chemotherapy (IC) for R/R AML. METHODS: Outcomes of R/R AML treated with 10-day decitabine and venetoclax (DEC10-VEN) were compared with IC-based regimens including idarubicin with cytarabine, with or without cladribine, clofarabine, or fludarabine, with or without additional agents. Propensity scores derived from patient baseline characteristics were used to match DEC10-VEN and IC patients to minimize bias. RESULTS: Sixty-five patients in the DEC10-VEN cohort were matched to 130 IC recipients. The median ages for the DEC10-VEN and IC groups were 64 and 58 years, respectively, and baseline characteristics were balanced between the 2 cohorts. DEC10-VEN conferred significantly higher responses compared with IC including higher overall response rate (60% vs 36%; odds ratio [OR], 3.28; P < .001), complete remission with incomplete hematologic recovery (CRi, 19% vs 6%; OR, 3.56; P = .012), minimal residual disease negativity by flow cytometry (28% vs 13%; OR, 2.48; P = .017), and lower rates of refractory disease. DEC10-VEN led to significantly longer median event-free survival compared with IC (5.7 vs 1.5 months; hazard ratio [HR], 0.46; 95% CI, 0.30-0.70; P < .001), as well as median overall survival (OS; 6.8 vs 4.7 months; HR, 0.56; 95% CI, 0.37-0.86; P = .008). DEC10-VEN was independently associated with improved OS compared with IC in multivariate analysis. Exploratory analysis for OS in 27 subgroups showed that DEC10-VEN was comparable with IC as salvage therapy for R/R AML. CONCLUSION: DEC10-VEN represents an appropriate salvage therapy and may offer better responses and survival compared with IC in adults with R/R AML.

Venetoclax with decitabine vs intensive chemotherapy in acute myeloid leukemia: A propensity score matched analysis stratified by risk of treatment-related mortality.

Hypomethylating agents (HMA) with venetoclax is a new standard for older/unfit patients with acute myeloid leukemia (AML). However, it is unknown how HMA with venetoclax compare to intensive chemotherapy (IC) in patients who are "fit" or "unfit" for IC. We compared outcomes of older patients with newly diagnosed AML receiving 10-day decitabine with venetoclax (DEC10-VEN) vs IC. DEC10-VEN consisted of daily venetoclax with decitabine 20 mg/m2 for 10 days for induction and decitabine for 5 days as consolidation. The IC cohort received regimens containing cytarabine ≥1 g/m2 /d. A validated treatment-related mortality score (TRMS) was used to classify patients at high-risk or low-risk for TRM with IC. Propensity scores were used to match patients to minimize bias. Median age of the DEC10-VEN cohort (n = 85) was 72 years (range 63-89) and 28% patients were at high-risk of TRM with IC. The comparator IC group (n = 85) matched closely in terms of baseline characteristics. DEC10-VEN was associated with significantly higher CR/CRi compared to IC (81% vs 52%, P < .001), and lower rate of relapse (34% vs 56%, P = .01), 30-day mortality (1% vs 24%, P < .01), and longer overall survival (OS; 12.4 vs 4.5 months, HR = 0.48, 95%CI 0.29-0.79, P < .01). In patients at both at high-risk and low-risk of TRM, DEC10-VEN showed significantly higher CR/CRi, lower 30-day mortality, and longer OS compared to IC. Patients at both high-risk and low-risk of TRM had comparable outcomes with DEC10-VEN. In conclusion, DEC10-VEN offers better outcomes compared to intensive chemotherapy in older patients with newly diagnosed AML, particularly in those at high-risk of TRM.

Prognostic value of measurable residual disease after venetoclax and decitabine in acute myeloid leukemia.

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.