Table 3.

Low-intensity single agent approaches.

Trial	Population	Regimen(s)	Response(s)	Survival	Comments
AML14 MRC [27]	Untreated AML or high-risk MDS unfit for intensive therapy	LDAC vs. hydroxyurea	CR = 18% vs. 1% (p < .00006)	OR for survival was 0.60 favoring LDAC (p = .0009)	There was no benefit among patients who did not achieve CR Survival was much improved with AZA for those treated with supportive care or LDAC but similar for those who received induction
AZA-AML-001 [28]	Newly diagnosed AML, age ≥65, WBC ≤15K, blasts >30%, ECOG ≤2, not eligible for HSCT with int/adverse cytogenetics	AZA 75 mg/m2 for 7 days every 28 days vs. CCR (SC, LDAC, or induction)	CR + CRi = 27.8% vs. 25.1%	Median OS favored AZA when censoring for subsequent therapy at 12.1 months vs. 6.9 months (p = .0190)
DACO-OI6 [30]	Newly diagnosed AML with int/adverse cytogenetics, age ≥65, WBC ≤40 K, ECOG ≤2	DEC 20 mg/m2 for 5 days every 28 days vs. TC (SC or LDAC)	CR + CRp = 17.8% vs. 7.8% (p = .001)	Median OS favored DEC 7.7 months vs. 5.0 months (log rank p = .037)	There were more serious AEs with DEC than TC
Ohio State [32]	Previously untreated AML, age ≥60, no WBC limit	DEC 20 mg/m2 IV for 10 days every 28 days	CR = 47% CRi = 17% ORR = 64%	Median OS = 55 weeks	Response rate was 50% for WBC ≥50 K, 74% for sAML, 75% for complex karyotype
SGI-110–01 [39]	Treatment naive AML not candidates for intensive induction due to age ≥65, ECOG 2, comorbidities or poor-risk cytogenetics	Guadecitabine 60–90 mg/m2 IV for 5 days every 28 days vs. guadecitabine 60 mg/m IV on days 1 −5 and 8–12 every 28 days	ORR (CR + CRp + CRi) = 57% vs. 48% (p = .43)	Median OS 10.5 months vs. 8.7 months (p = .89)	Toxicities were similar. CR and CRp were 40–45% for both arms
AML16 [40]	Untreated AML or high-risk MDS unfit for intensive therapy, age ≥60	LDAC vs. clofarabine 20 mg/m2 IV for 5 days every 4–6 weeks	ORR (CR + CRi) = 19% vs. 38% (p < .001)	2-year OS was 12% vs. 13%	Greatly increased toxicity in the clofarabine arm led to similar survival, clofarabine required significantly more supportive care including hospitalization
AML16 and LI-1 [42]	Untreated AML or high-risk MDS unfit for intensive therapy, age ≥60	LDAC vs. sapacitabine 300 mg PO BID on days 1–3 and 8–10 every 28 days	ORR (CR + CRi) = 27% vs. 16% (p = .09)	2-year survival 12% vs. 11% (p = .2)	Toxicities were similar with more grade 3/4 diarrhea with sapacitabine
SGN33A-001 [43]	CD33+, previously untreated AML ineligible for or declined conventional treatment	Vadastuximab 40mcg/kg q3wks ×2 cycles	CR + CRi = 54%	Survival data not yet mature	Trials subsequently halted due to increased VOD with HSCT

LDAC: cytarabine 20 mg SubQ BID for 10 days every 28–42 days.

SC: supportive care.

AZA: azacitidine (Vidaza).

DEC: decitabine (Dacogen).