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. 2022 Apr 16;14(8):2025.
doi: 10.3390/cancers14082025.

Azacitidine Plus Venetoclax for the Treatment of Relapsed and Newly Diagnosed Acute Myeloid Leukemia Patients

Sylvain Garciaz  1   2 , Marie-Anne Hospital  2 , Anne-Sophie Alary  3 , Colombe Saillard  2 , Yosr Hicheri  2 , Bilal Mohty  2 , Jérôme Rey  2 , Evelyne D'Incan  2 , Aude Charbonnier  2 , Ferdinand Villetard  2 , Valerio Maisano  2 , Laura Lombardi  2 , Antoine Ittel  4 , Marie-Joelle Mozziconacci  4 , Véronique Gelsi-Boyer  4   5 , Norbert Vey  1   2
Affiliations

Azacitidine Plus Venetoclax for the Treatment of Relapsed and Newly Diagnosed Acute Myeloid Leukemia Patients

Sylvain Garciaz et al. Cancers (Basel). .

Abstract

Venetoclax (VEN) belongs the BH3-mimetic class that selectively targets BCL-2, activating apoptosis. The combination of VEN and azacitidine (AZA) has changed the paradigm of treatment of newly diagnosed (ND) acute myeloid leukemia (AML) patients ineligible for intensive chemotherapy. There is scarce evidence for the use of VEN-AZA for relapsed or refractory (R/R) AML. We compared the outcome of 39 R/R AML and 38 ND AML patients treated between 01/20 and 12/21. The median age was 69 (22-86) and 73 (61-81) in the R/R and ND groups, respectively. Adverse cytogenetics were found in 36% of patients in the R/R group and 59% of patients in the ND group. Overall response rate was 37% in R/R AML, including 13% CR, 8% CRi, 3% PR and 13% MLFS, and 58% in the ND AML, including 32% CR, 13% CRi and 13% MLFS. Adverse cytogenetics was associated with treatment failure in the R/R group (Relative Risk = 0.13, p = 0.005). Median overall survival (OS) was 5.9 months in the R/R group and 9.4 months in the ND group. Median OS was 2.2 months in the adverse cytogenetics group versus 8.7 months in the intermediate cytogenetics group in the R/R group (p = 0.02). Median leukemia-free survival was not different between the two groups (9.4 months and 10.3 months), indicating that VEN-AZA can be an efficient salvage treatment for selected R/R AML patients. In conclusion, VEN-AZA is a promising treatment for ND AML and for selected R/R AML patients.

Keywords: acute myeloid leukemia; venetoclax.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Treatment modalities. Patients received 7 days of AZA (blue). Number of VEN weeks of treatment (different shades of purple) during cycle 1 and subsequent cycles depends on patients age and comorbidities, disease response, and hematological toxicities.
Figure 2
Figure 2
Bar graph showing the number of patients with detected mutations in the ND and R/R groups of patients treated with VEN–AZA.
Figure 3
Figure 3
Bar graphs showing response rates on day-28 and day-56 in the first line cohort (A), the R/R cohort (B) and the VIALE-A trial eligible patients (C). Bar graphs showing response rate on day-56 according to cytogenetics (D), TP53 and/or RAS mutation (E) and % of VEN dose at cycle 1 (F).
Figure 4
Figure 4
Kaplan–Meier analyses showing overall survival (OS) in the R/R AML group (A) and in the ND AML group (B) of patients according to cytogenetics, OS and event-free survival (EFS) according to TP53 and/or RAS status (C,D) and leukemia-free survival (LFS) of responding patients in the R/R group ND AML group according to the disease status before starting treatment (ND versus R/R, (E) or response on day-56 (MLFS versus CR/CRi/PR, (F).
Figure 5
Figure 5
Forest plots showing clinical and molecular factors associated with response (RR > 1) or the lack of response (RR < 1) in the ND AML group (A) and the R/R AML group (B). Blue and purple lines indicate risk factors associated with response or lack of response, respectively.
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