Talha Badar: In view of recent approval of IDH1i in MDS brief tweetorial

Talha Badar, Assistant Professor of Oncology at Mayo Clinic Comprehensive Cancer Center, posted on X/Twitter:

”Weekend review!

In view of recent approval of IDH1i in MDS.
IDH1m present in 3% of pts with MDS.
Earlier approved for RR AML with IDH1m and AML ineligible for IC.
Brief tweetorial.

Retrospective analysis suggests, MDS points with neutropenia, regardless of IPSS-R, more enriched with IDH1/2 and these can potentially targeted with IDHi.

First in human, single arm phase dose escalation study, 16 pts Rx @ 500 mg OD. CR 44%, 60% maintained response at 1 year (NCT02074839).

The idiome phase 2 study by the GFM group; evaluated IDHi in MDS failing HMA or HR-MDS. 32 pts treated, ORR was 69%, CR 46%. DOR 7.4 mo, OS 14 mo (91% response rate in treatment naive HR-MDS).

20 pts with MDS Rx with Olutasidenib (highly selective and potent) IDH1i, 6 alone and 14 with AZA. Clinical responses were seen in 33% with alone and 73% with combo.

Recently published study on Olutasidenib in MDS/AML 78 pts (46 with combo) Rx, response rate in the range of 40%, comparable b/w mono and combo therapy.

After FDA breakthrough designation, enrollment was expanded: 19 pts were Rx (78.9% with HMA failure) mOS 35.7 mo. 15/18 had ORR,CR 39% mDOR not reached at data cut off. Median time to response 1.9 mo Approval is based on study of 18 pts ONLY!

Conclusion Albeit study with small sample size and IDH1m occurrence in only 3-4% of MDS Seems to be effective target, highly encouraging responses post HMA failure! ORR up-to 90% in treatment naive MDS.”

Source: Talha Badar/Twitter