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

Abstract

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.

Keywords: acute myeloid leukemia (AML); decitabine; intensive chemotherapy; refractory; relapsed; venetoclax.

© 2021 American Cancer Society.

Figures

Fig. 1

a.Event-free survival (EFS), and b. Overall survival (OS) in patients with relapsed or refractory acute myeloid leukemia who received salvage therapy with 10-day decitabine with venetoclax (DEC10-VEN) versus intensive chemotherapy (IC); c. exploratory subgroup analysis for OS in unmatched populations. The dotted line represents hazard ratio of 1.00. Only patients receiving FLT3 inhibitors were chosen for the subgroup analysis comparing outcomes in FLT3mut AML. All 16 patients treated with DEC10-VEN received FLT3 inhibitor including gilteritinib (n=7), sorafenib (n=6), midostaurin (n=3); and all 48 selected patients treated with intensive chemotherapy received FLT3 inhibitor including sorafenib (n=33), crenolanib (n=10), gilteritinib (n=2), midostaurin (n=2), and ponatinib (n=1). ECOG PS = Eastern Co-operative Oncology Group performance status, sAML = secondary AML, AHD = antecedent hematological disorder, HMA = hypomethylating agent, SCT = allogeneic stem-cell transplantation.