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Talha Badar: Brief review focusing on VEN and HMA triplets in AML

Photo taken from Talha Badar/Twitter

Feb 13, 2024, 08:00

Talha Badar: Brief review focusing on VEN and HMA triplets in AML

Talha Badar, Hematologist/Oncologist at Mayo Clinic in Jacksonville, Florida, shared a thread on X/Twitter:

“Weekend review: Sub-group of Acute Myeloid Leukemia (AML) with targetable mutation have sub-optimal response of Venetoclax (VEN) with Hypomethylating agents (HMA), for example, FLT3m, KMT2A OR sequencing targeted therapy post-VEN have modest responses, for example, IDH1/2i.

Brief review focusing on VEN+HMA triplets in AML:

Phase I/II VEN+AZA with Gilt (MTD; 80 mg) in ND and RR FLT3m AML
C1 AZA 7d, VEN 28d, Gilt 28d
VEN and Gilt held if d14 BM hypoplastic/ <5% blast
C2 AZA 5d, VEN 7d, Gilt 28d
30 ND, CR/CRi 96% 18 mo RFS/OS 71/72%. 2
2 RR, CR/CRi 27%

VEN (14-21d), DEC (10d) and Quizartinib (30-40mg daily);
28 pts (23 RR AML)
RR gp CRc 78%, mOS 7.8 mo
ND gp CRc 100%, mOS 19/8 mo with/without alloHCT.
G3/4 non-hem AE 30-40%, 60d mortality 5%

IVO, VEN +/- AZA in IDH1m
Phase1b/II study on 31 pts. AE were G1/2 91%
CRc= IVO + VEN + AZA vs IVO + VEN 90%vs 83%; OS NR vs 42 mo

Phase 1: AZA+VEN and APR246 in TP53m AML
49 pts No DLT, sAE 27%
CR 38%, ORR 64%
Aprea myeloid program was stopped after it fails to meet PE of CR in HR-MDS.

Ph1b/II study evaluated VEN+HMA+Magro triplet in AML;
43 pts/ 27 TP53m: CR 63%/ 83% TP53m. 12 mo OS 53 vs 83%.
ENHANCE-III trial comparing Ven/HMA to Ven/HMA+ Magro halted; Magro demonstrated futility and increased the risk of death

VEN+HMA with Tagraxofusp (TAG)
TAG 12 μg/kg/d for 3d, with 7-d AZA +/− 21-d VEN.
Expansion cohort of 26 pts ELN adverse risk (50% TP53 mutated), ORR 69%, 39% CR, 19% CRi
PFS 14 and mOS 8.5 mo