Talha Badar: Weekend review. Venetoclax for NPM1m

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

“Weekend review
Venetoclax for NPM1m AML
Historically, this group of pts responds great to intensive chemotherapy: CR upto 85% and 5 yr OS 40-50%, and preferred even in elderly with good PS  How venetoclax based therapy is evolving for this gp of pts

2/Link to study/
HMA+ VEN for newly diagnosed NPM1m AML
Long-term fu of phase 1b study of VEN+HMA, 17% of pts had NPM1m AML; reported CR/CRi rate of 79%. With a median fu of 29 and 40 mo with Aza and Dec combinations: median duration of response not reached.

3/Link to study/
HMA+ VEN for newly diagnosed NPM1m AML
LDAC plus Venetoclax, phase Ib/II study 13 pts had NPM1 with CR/CRi rate was 89%.

4/Link to study/
VIALE-A phase III study (n=27) the overall response rate was 93% and the 2-year OS was 75% for patients harboring a NPM1 mutation.

5/Link to study/
HMA+ VEN for newly diagnosed NPM1m AML Real world analysis from Mayo Clinic Comprehensive Cancer Center reported CR/CRi rate > 80% with 2 yrs OS > 70%

6/Link to study/
Venetoclax combination for RR AML
In retrospective analysis HMA/LDAC combo with VEN showed CR/CRi of 67%. Survival on subset not reported.

7/Link to study/
In another real world retrospective analysis, VEN+HMA for RR NPM1m AML : CR/CRi, 46%; ORR, 62%; OR, 4.53; 95% CI, 1.31-15.66; P = .02) suggesting favorable outcome.

8/Link to study/
Venetoclax combination for NPM1 AML with molecular relapse
30-40% NPM1m will relapse. Molecular relapse with inevitably lead to florid relapse. retrospective analysis,56/79 (84%) pts responded, 71% MRD 41/79 bridged to allo-HCT
2 yrs OS 67%

9/Link to study/
Venetoclax combination for NPM1 AML with molecular relapse
Another study on 12 NPM1m AML pts with molecular relapse treated with LDAC plus venetoclax
11/12 (92%) of pts achieved MRD negativity.
At a median follow up of 12 months, none relapsed.

Summary:
VEN+HMA demonstrates comparable outcome to intensive chemotherapy
Successfully allo-HCT.
Excellent MRD – rates after molecular relapse: prospective study ongoing: NCT04867928
PIII ongoing to determine if intensive chemo is better than VEN +HMA(VINCENT Trial)”

Source: Talha Badar/X