Acute Myeloid Leukemia (Age ≥18 years): IDH1 of IDH2 mutation or FLT3 mutation…Venetoclax-based therapy with decitabine noted as preferred...

Acute Myeloid Leukemia (Age ≥18 years): IDH1 of IDH2 mutation or FLT3 mutation…Venetoclax-based therapy with azacitidine noted as category 1 and preferred...

In the biomarker evaluable population, FLT3 mutation was detected in 42 (15%) and 22 (19%) patients in the venetoclax+azacitidine and azacitidine groups. Composite complete remission (CRc, complete remission [CR]+CR with incomplete hematologic recovery [CRi]) rates (venetoclax+azacitidine /azacitidine) for FLT3 mutant patients were 67%/36%, median duration of remission (DoR) was 17.3/5.0 months, and median OS was 12.5/8.6 months. The CRc rates among FLT3 wild-type were 67%/25%, median DoR 18.4/13.4 months, and median OS 14.7/10.1 months. When treated with venetoclax+azacitidine, patients with FLT3 mutations and FLT3 wild-type had similar outcomes.

Among treatment-naïve predominantly elderly pts with AML ineligible for intensive therapy, the combination regimen of AZA+VEN led to statistically significant and clinically meaningful improvement in response rates and OS as compared to AZA, with a manageable safety profile.

...a documented FMS-like Tyrosine Kinase (FLT3) mutation in bone marrow or peripheral blood, as described in the protocol....

...Pazienti che hanno ricevuto una precedente diagnosi di leucemia mieloide acuta con mutazione di NPM1 con o senza concomitante mutazione di FLT3-TKD o FLT3-ITD3. ...

Thirty FLT3m AML patients with R/R disease, treated at Mayo Clinic with HMA+Ven (with/without gilteritinib [Gilt]) between 2019 and 2022, were analyzed….Univariate analysis for OS showed a significantly better OS with FLT3m ITD subtype (P<0.0001), FLT3 allelic ratio <0.5 (P=0.03), and TET2 mutation (P=0.007)….Hypomethylating agent plus Ven based combination seem to be effective as salvage therapy in patients with FLT3m AML.

All patients achieved complete remission on day 21 and day 28….The sequential use of venetoclax followed by midostaurin in combination with low dose chemotherapy or HMA for newly diagnosed AML, FLT3-mutant patients who are unfit for intensive chemotherapy seems to be a promising approach with an acceptable toxicity profile.

Pts received decitabine 20 mg/m2 on D1-10 until CR/CRi, followed by 5-day cycles. VEN dose was 400 mg daily but held on C1D21 if D21 bone marrow (BM) had ≤5% blasts….DEC10-VEN offered high rates of CR/CRi, negative MRD, favorable OS and RFS across several genomic subgroups of treatment-naïve AML including NPM1, FLT3, IDH1/2...

CONTRADICTED EVIDENCE: Of 26 newly diagnosed AML patients, the CR/CRi rate was 53.8%. The median DOR and OS were 6.9 months and not reached, respectively. Of 39 R/R AML patients, the CR/CRi rate was 38.5%. The median DOR and OS were both 8.1 months. Responders to HMA and venetoclax were enriched for TET2, IDH1, and IDH2 mutations, while nonresponders were associated with FLT3 and RAS mutations.

All AML pts who received treatment with aza/ven, dec/ven or LDAC/ven as either initial induction or for RR disease...A total of 130 pts were treated with ven combo therapy with 18 pts (13.8% of all pts) receiving a subsequent alloSCT. While pts with DNMT3A, NPM1, IDH1/2 and FLT3 mutations had a high response rate to ven therapy...Only DNMT3A mutations were statistically significantly associated with a high response rate prior to alloSCT (ORR 100%, CR/CRi 63%, p=0.01).

Ven was given in combination with HMA, low dose cytarabine (LDAC), or IC in 35 (83.3%), 6 (14.3%), and 1 (2.4%) pt respectively....CR/CRi rates were higher for pts with FLT3 (p=.040) and NPM1 mutations (p=.04).

Complete response (CR)+CR with partial hematologic recovery (CRh) rates in FLT3mut pts (Ven+Aza/Pbo+Aza) were 65% (95% CI:48%-79%)/18% (5%-40%)...Among pts with FLT3-ITD, CR+CRh rates (Ven+Aza/Pbo+Aza) were 61% (95% CI: 41%-79%)/23% (5%-54%)...CR+CRh rates in pts with FLT3-TKD were 69% (95% CI: 39%-91%)/20% (3%-56%) with mDoR 18.3 (95% CI: 3.0-NR)/NR (15.1-NR) mos.

The overall CR/CRi rate with VEN‐HMA was 60% (94% in treatment‐naïve AML and 42% in r/r AML)….VEN‐HMA is associated with encouraging efficacy in FLT3m AML among both newly diagnosed unfit and r/r patients.

VEN combined with high-dose cytarabine or high-dose cytarabine and idarubicin was well tolerated and effective in children and young adults with relapsed or refractory AML. Enrollment continues to refine estimates of response rate. VEN window response is associated with BH3 dependence and end of cycle 1 response rates. Targeting BCL-XL or FLT3 may improve response to combination therapy...

The CR/CRi rates were 83.7% for pts with IDH1/IDH2 mutations, 84.6% for pts with NPM1 mutations, 59.5% for pts with TP53 mutations, and 53.3% for pts with FLT3 mutations (Table 2)….VEN + HMA or LDAC has efficacy across multiple molecular markers in AML