Table 1.

Experimental treatments (phase 2/phase 3 studies) of IPSS lower-risk MDS patients refractory/relapsed after ESAs and severely anemic/RBC transfusion dependent

StudyDoses# PatientsInclusion criteriaResults (HI-E per IWG criteria) %
Azacitidine + ESAs phase 248  75 mg/m2 daily for 5-d/28-d cycle plus EPO β 60 000 U/wk 49 sEPO >500 U/L or ESA R/R 34.7 
Oral azacitidine (cc-486) (www.clinicaltrials.gov; #NCT01566695) 300 mg daily for 21-d/28-d cycle Ongoing RBC TD and PLT <75 × 109/L Ongoing 
Lenalidomide phase 349  10 mg os daily 28-d cycle 239 (160) sEPO >500 U/L or ESA R/R 26.9 
Lenalidomide + ESAs phase 350  10 mg daily for 21-d/28-d cycle plus EPO β 60 000 U/wk 131 (65) sEPO >500 U/L or ESA R/R 39.4 
Luspatercept phase 251  1 mg/kg* SC every 3 wk 32 sEPO >500 U/L or ESA R/R with/without RS 69 
Galunisertib phase 252  150 mg os BID for 14-d/28-d cycle 41 sEPO >500 U/L or ESA R/R 26 
StudyDoses# PatientsInclusion criteriaResults (HI-E per IWG criteria) %
Azacitidine + ESAs phase 248  75 mg/m2 daily for 5-d/28-d cycle plus EPO β 60 000 U/wk 49 sEPO >500 U/L or ESA R/R 34.7 
Oral azacitidine (cc-486) (www.clinicaltrials.gov; #NCT01566695) 300 mg daily for 21-d/28-d cycle Ongoing RBC TD and PLT <75 × 109/L Ongoing 
Lenalidomide phase 349  10 mg os daily 28-d cycle 239 (160) sEPO >500 U/L or ESA R/R 26.9 
Lenalidomide + ESAs phase 350  10 mg daily for 21-d/28-d cycle plus EPO β 60 000 U/wk 131 (65) sEPO >500 U/L or ESA R/R 39.4 
Luspatercept phase 251  1 mg/kg* SC every 3 wk 32 sEPO >500 U/L or ESA R/R with/without RS 69 
Galunisertib phase 252  150 mg os BID for 14-d/28-d cycle 41 sEPO >500 U/L or ESA R/R 26 

Of the numerous studies performed in this clinical setting, reported here are some of the most relevant phase 2/3 studies, as referenced and quoted in the text.

BID, twice daily; ESA R/R, erythropoietic stimulating agent relapsed/refractory; os, orally; RS, ring sideroblasts; sEPO, endogenous serum EPO; TD, transfusion dependent.

*

Starting dose, titration up to 1.75 mg/kg.

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