Talha Badar: Outcome of patients progressing after venetoclax based therapies
Talha Badar, Hematologist/Oncologist at Mayo Clinic in Jacksonville, Florida, shared a post on X/Twitter:
” Weekend review
- Outcome of patients progressing after venetoclax based therapies
- Mechanism of venetoclax resistance
- Possible strategies to overcome resistance
Outcome of patients progressing after VEN+HMA is extremely poor with median survival 3-6 months
Mechanism of VEN resistance:
-MCL1 over-expression
-Acquired mutations in BCL-2
-BAX mutation
-FLT3 mutations/ FLT3 F691
-RAS mutations
-TP53 Mutations
-PTPN11 mutations
RWD on therapies post Venetoclax
FLT3, IDH1 or IDH2 inhibitors post venetoclax
Multi-center retrospective analysis, 53 pts, ORR (CR, CRi, PR, MLFS) 17.7%:
Median OS 4.2 months
RAS, TP53 predictive of poorer outcome
RWD on therapies post Venetoclax
CLAD/LDAC/Ven post VEN+HMA
Our center experience on 39 pts RR VEN+ HMA, CR/CRi 28%, median DOR 3.4 months.
Median OS 4.6 months, among pts who achieve CR 8.1 month
Intensive chemotherapy after VEN+HMA
RWD from our COMMAND consortium.
ORR 27%, CR 23%.
CPX-351 post VEN plus HMA ORR 33%.
23% proceeded to allo-HCT
Median OS 5.8 mo, with allo-HCT 8.2 months
Possible strategies to overcome resistance
Ven +BH3 mimetic
Limited duration of Ven? prevent emergence of resistance
Upfront Ven, HMA+Flt3i
MCL1i (limited by cardiotoxicity)
TP53m—> targets APR-246, Magro: limited by toxicity/efficacy. Allo-HCT in CR1″
Source: Talha Badar/X