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Venetoclax-based salvage therapy followed by Venetoclax and DLI maintenance vs. FLAG-Ida for relapsed or refractory acute myeloid leukemia after allogeneic stem cell transplantation

Abstract

We retrospectively compared the outcomes of 20 patients receiving Venetoclax + low-dose Cytarabine + Actinomycin D (ACTIVE) with 29 patients receiving FLAG-Ida as salvage therapy for relapsed or refractory AML (R/R AML) after alloSCT. The groups were statistically balanced according to age, performance status, cytogenetics, and previous treatment. The overall response rate (CR + CRp + MLFS) of ACTIVE was 75% (15/20) in comparison to 66% (19/29) in the FLAG-Ida group (p = 0.542). The cumulative CR + CRp rate was significantly higher in the ACTIVE group compared to FLAG-Ida (70% (14/20) vs. 34% (10/29), respectively, p = 0.02). All three patients failing previous Venetoclax therapy and five out of seven patients with previous FLAG-Ida exposure achieved a CR/CRp after ACTIVE induction. ACTIVE patients survived longer compared to FLAG-Ida patients (13.1 vs. 5.1 months, respectively, p = 0.032). The treatment-related mortality was 0% in the ACTIVE group and 34% (10/29) in the FLAG-Ida patients (p = 0.003). The cumulative incidence of relapse did not differ between the two treatment groups. ACTIVE appears to have comparable antileukemic activity and lower toxicity compared to FLAG-Ida resulting in improved survival. Patients with Venetoclax or FLAG-Ida exposure responded to ACTIVE.

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Fig. 1: Molecular patterns and responses in ACTIVE and FLAG-Ida patients.
Fig. 2: Survival of ACTIVE and FLAG-Ida patients.
Fig. 3: Cumulative incidence of relapse.
Fig. 4: Survival of ACTIVE patients based on the MRD status.
Fig. 5: Subgroup analysis.

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Contributions

AZ: study design, data collection, statistical analysis, writing the manuscript LG: study design, writing the manuscript, study supervision. VV, KM, LD: data collection. RP, IT, VP: study design and implementation of the research. TZ, VS: statistical analysis. All authors provided critical feedback and helped shape the research, analysis and manuscript.

Corresponding author

Correspondence to Andrius Zucenka.

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Competing interests

Venetoclax was provided by Abbvie via patient early access program. AZ, RP, LG—Abbvie: Travel grants, honoraria; VV, KM, LD, IT, VP, TZ, VS—none.

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Zucenka, A., Vaitekenaite, V., Maneikis, K. et al. Venetoclax-based salvage therapy followed by Venetoclax and DLI maintenance vs. FLAG-Ida for relapsed or refractory acute myeloid leukemia after allogeneic stem cell transplantation. Bone Marrow Transplant (2021). https://doi.org/10.1038/s41409-021-01416-5

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