Table 2.

New drugs for high-risk patients.

New Active Principle	Mechanism of Action	Efficacy in Evaluable Patients	Clinical Trial
Guadecitabine	HMA, inhibits DNA/RNA methyltransferases	N = 105 ORR 51% treatment naïve patients ORR 43% R/R patients	NCT01261312 phase I/II
Pevonedistat + azacytidine	NAE first inhibitor	N = 58 CR rate of 51% with a median duration of response of 34 months	NCT02610777 phase II
Venetoclax + azacytidine	BCL-2 inhibitor	N = 78 CR rate of 40%	NCT02942290 phase Ib
Nivolumab + ipilimumab +/− azacytidine	Anti PD1 and anti CTLA4 immune checkpoint inhibitors	N = 26 CR rate of 18% in HMA failure cohort (N = 11) CR rate of 33% in HMA naïve cohort (N = 15)	NCT02530463 phase II
Sabatolimab + decitabine	Humanized anti-TIM-3 antibody	N = 16 CR rate of 50%	NCT03066648 phase I
Magrolimab + azacytidine	Anti CD47 immune checkpoint inhibitor	N = 33 ORR 91%, CR rate of 42%	NCT03248479 phase I
Flotetuzumab	CD123 X CD3 bispecific antibody	N = 14 Patients with either R/R AML or MDS ORR 43%	NCT02152956 phase I
Ivosidenib	mutant IDH1 inhibitor	N = 26 ORR 69%, CR rate of 46%	NCT03503409 phase II
Enasidenib	Mutant IDH2 inhibitor	N = 17 ORR 53%	NCT01915498 phase I

HMA, hypomethylating agent; DNA, deoxyribonucleic acid; RNA, ribonucleic acid; NAE, NEDD8-activating enzyme; ORR, overall response rate; CR, complete remission; TIM-3, T-cell immunoglobulin domain and mucin domain-3; MDS, myelodysplastic syndrome; IDH1, isocitrate dehydrogenase 1; IDH2, isocitrate dehydrogenase 2; r/r, relapsed/refractory; AML, acute myeloid leukemia.