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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

Bone Marrow Transplantation volume 56, pages 2804–2812 (2021)Cite this article

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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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Authors and Affiliations

  1. Faculty of Medicine, Institute of Clinical Medicine, Vilnius University, Vilnius, Lithuania

    Andrius Zucenka, Vilmante Vaitekenaite, Kazimieras Maneikis, Regina Pileckyte, Valdas Peceliunas & Laimonas Griskevicius

  2. Hematology, Oncology and Transfusion Medicine Center, Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania

    Andrius Zucenka, Vilmante Vaitekenaite, Kazimieras Maneikis, Linas Davainis, Regina Pileckyte, Igoris Trociukas, Valdas Peceliunas, Tadas Zvirblis, Vytautas Staras & Laimonas Griskevicius

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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.

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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 56, 2804–2812 (2021). https://doi.org/10.1038/s41409-021-01416-5

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