Table 2.

Emerging therapies for LR-MDS

Agent	Mechanism of action	Route of administration	Suggested patient population	Single or combination	Response rate	Reference
Roxadustat	Hypoxia-inducible factor (HIF) inhibitor	Oral	LR-MDS (non-del5(q)) with low transfusion burden, sEPO ≤400 U/L	Phase 3 study ongoing ROXA vs Placebo	Dose finding cohort results: N=24. HI-E=54%, TI=38% after 28 wk of treatment. TI=78% at higher dose level 2.5mg/kg	46
Imetelstat	Telomerase inhibitor	Intravenous	LR-MDS (non del5(q))with high transfusion burden and ESA failure	Phase 2/3 iMERGE study	HI-E=68%, TI for 8 wk=42%, TI for >24 wk=29%, CR=13% and CRi=10%. No PR. High rates of myelosuppression	47,48
H3B-8800	Spliceosomal inhibitor: synthetic lethality	Oral	LR-MDS with spliceosome mutations	Phase 1 dose escalation study	14% HI, no CR/PR PD studies demonstrated dose dependent splicing modulation	49
APR-246	TP53 modifier	Intravenous	Treatment naïve HR-MDS/AML with TP53 mutation	Combined with HMA	RR=75-87%, CR=55% CR in phase 2 when combined with HMA	50,51
Ivosidenib	IDH1 inhibitor	Oral	R/R MDS with IDH1 mutation (N=12)	Phase 1 single agent	CR=5/12 and RR=11/12	52
FT-2102	IDH1 inhibitor	Oral	MDS and AML (N=36)	Phase 1/2 single agent and + HMA	CR/CRi 38% single agent (N=16) CR=27% combo with HMA	53
Enasidenib	IDH2 inhibitor	Oral	R/R MDS with IDH2 mutation (N=17)	Single or combined	1/17=CR and 10/17=Response	54

CR = complete remission, CRi = complete remission with incomplete count recovery, ESA = erythroid stimulating agent, HI-E = erythroid hematological improvement, HMA = hypomethylating agent, LR = lower risk, PR = partial response, R/R = relapsed/refractory, RR = response rate, sEPO = serum erythropoetin level, TI = transfusion independence.