Pb1861: efficacy and toxicity of venetoclax plus hypomethylating agents in the real life of acute myeloid leukemia

Topic: 4. Acute myeloid leukemia - Clinical Background: Venetoclax (VTX) plus hypomethylating agents (HMA) regimens are routinely used for newly diagnosed (ND) acute myeloid leukemia (AML) patients (pts) unfit for intensive treatment or refractory/relapsed (RR). Unsponsored studies are ongoing and real-life data about response and toxicity are still not fully clear. Aims: To describe outcome and toxicity of VTX plus HMA combination regimen in AML pts in a real-life setting. Methods: In this monocentric retrospective study we evaluated 60 AML pts consecutively treated between 2018 and 2022 at our Institution. We reviewed data about history disease, treatment response and toxicity. We defined Overall Survival (OS) as the time between start of therapy and death for any cause or last follow-up and Disease-Free Survival (DFS) as the time between first response and relapse, death or last follow-up. OS and DFS were estimated by Kaplan-Meier product-limit method. Results: Out of 60 AML pts, 32 were ND and 28 RR (median of previous lines of therapy: 2), 90% were treated with azacitidine and 10% with decitabine. Median age was 67 years (IQR: 58-76), 33 pts (55%) were considered unfit at diagnosis. Median number of cycles was 2 [IQR: 2-4] with a median FU of 5.5 mo [IQR 2.5-11.5]. The overall response rate (ORR) was 63% (38/60), 29% subsequently received allogeneic bone marrow transplant and relapse occurred in 21%. Composite complete remission was achieved in 35% (21/60: 14 CR and 7 CRi). CCR was obtained in 17/32 ND pts (53%) and 4/28 RR pts (14%). CCR was not statistically different among ELN categories (p>0.7). Measurable residual disease negative status (MRD-), assessed by PCR or MPFC (blasts <0.1%), was achieved in 48% of pts in CCR (10/21). Median time to best response was 2.3 months (mo) (IQR: 0.9-4.7). Median OS and DFS were 6.1 mo and 7.7 mo, respectively. DFS in MRD negative pts was 9.3 mo. DFS was not different in ND or RR pts (p=0.628). After adjusting for cycle of first response in a bivariable Cox model, DFS was significantly higher in CCR patients vs RP+MLFS pts (HR=7.9, 95%CI: 1.7-36.2, p=0.008) (Figure). Most common adverse events (G>=3, CTCAE 5.0) were infections and haematological toxicity. Infections represented a major problem in pre-remission cycles (67% in cycle 1 and 52% in cycle 2) and sharply decreased in subsequent cycles. Neutropenia occurred in 42% (cycle 1) and 50% (cycle 2) of pts but remained a challenging issue after remission (nearly 30% after cycle 3). Summary/Conclusion: In the studied population (including both ND and RR pts) we report a high ORR with a high and fast CCR rate (35% after a median of 2.3 mo). Importantly, half of CCRs were deep (MRD-). A recent Italian study (AVALON study) reported similar rates (CCR 39%) obtained in short time (2.2 mo). Median OS and DFS were all comparable. The MRD- rate, despite the limited number of pts, is encouraging and higher than reported (in 2022 by Ong). Our study confirms that VTX plus HMA combination therapy is an attractive option for both ND and RR AML pts. The higher DFS obtained in CCR vs PR/MLFS pts suggests that the only desirable response is CCR. CCR is less frequently achievable in RR pts. However, if obtained, duration is similar to ND pts. Toxicity is manageable but special attention should be paid to minimize neutropenia occurring in remission. The preliminary results of this study show a favorable response profile of a low intensity regimen in unselected AML pts in different disease phases. Achievable profound responses and manageable toxicity translate in good survival data. Future analysis on a higher number of pts with a longer follow-up is necessary to confirm these results.Keywords: Acute myeloid leukemia, Venetoclax, Hypomethylating agents, Real world data