Table 2.
Preliminary results of agents undergoing phase III trial for upfront management of acute myeloid leukemia in older adults unfit for intensive chemotherapy
| Study drugs/arms | Phase, N | Response rate | Median OS | Ongoing phase III trial |
|---|---|---|---|---|
| Guadecitabine, (2 different doses)[57] | Randomized phase 2, n=107 | 53% CR/CRi, no difference among high-risk AML or sAML | 10 months, no difference among high-risk AML or sAML | Guadecitabine vs. treatment choice (NCT02920008) |
| Ten-day decitabine[50] | Phase 2, n=53 | 64% CR/CRi (74–75% CR/CRi among sAML or tAML and high-risk AML)* | 55 weeks | 10-day decitabine vs. 7+3 (NCT02172872) |
| Pracinostat and azacitidine[56] | Phase 2, n=50 | 52% CR/CRi/MLFS | 62% at 1-year, median OS 13 months in high- risk AML | Azacitidine with or without pracinostat (NCT03151408) |
| Pevonedistat and azacitidine[55] | Phase 1b, n=64 | 50% CR/CRi/PR, no difference in de novo vs sAML, and int vs high risk AML; 80% CR/PR in TP53 mutated AML (n=5) | 7 months | Azacitidine with or without pevonedistat in low-blast AML, CMML, high-risk MDS (NCT03268954) |
| Glasdegib with LDAC, decitabine or 7+3[89] | Phase 1b, n=52 including 7 MDS | CR/CRi 9%, 29% and 54% | 4, 11 and 35 months | Azacitidine or 7+3, with or without glasdegib (NCT03416179) |
| Ivosidenib or enasidenib and azacitidine[84] in IDH mutated† | Phase 1b/2, n=17 (ongoing) | 53% CR/CRi/PR | NA | Azacitidine with or without ivosidenib (NCT03173248) |
| Azacitidine and nivolumab[90]‡ | Phase 2, n=10 (ongoing) | 55% CR/CRp | NA | 4-arm phase II/III trials, azacitidine alone, with nivolumab or midostaurin, or decitabine and cytarabine (NCT03092674) |
| Uproleselan (GMI-1271) and 7+3[54]¶ | Part of a phase 2 trial, n= 25 | 72% CR/CRi, 69% among sAML | 52% at 1 year; median OS of 10 months for sAML | 7+3 with or without uproleselan (phase II/III trial, NCT03701308) |
AML acute myeloid leukemia, CMML chronic myelomonocytic leukemia, CR complete remission, CRi CR with incomplete count recovery, CRp CR with incomplete platelet recovery, MDS myelodysplastic syndrome, MLFS morphologic leukemia-free state, N number of patients in the trial, NA not available, OS overall survival, PR partial remission, sAML secondary AML, tAML therapy-related AML
Another study[51] also demonstrated a high response rate among patients with AML and myelodysplastic syndrome with high-risk cytogenetic (67%) and TP53 mutation (100%) with 10-day decitabine.
An ongoing phase 1 trial of single-agent ivosidenib in newly diagnosed IDH1 mutated AML patients demonstrated a CR/CR with incomplete hematological recovery (CRh) of 41% among 34 patients treated with a dose of 500 mg daily.[91] Early results of a phase 1b/II sub-study from the BEAT AML Master Trial demonstrated a CR/CRi rate of 43% with enasidenib monotherapy in 23 older adults with newly diagnosed AML.[92] Another phase 1 trial of ivosidenib or enasidenib in combination with intensive chemotherapy in IDH mutated AML (n=134) demonstrated high rates of CR/CRi/CRp among de novo and sAML patients treated with ivosidenib (93% and 46%) and enasidenib (73% and 63%). MRD negative rates were 89% and 58% for IDH1 and IDH2 mutated patients, respectively.[93]
Nivolumab in combination with idarubicin and intermediate-dose cytarabine in newly diagnosed AML or high-risk MDS patients aged 18–65 years resulted in a CR/CRi of 77%, MRD negativity rate of 53% and median OS of 18 months (versus 13 months in historical cohort, p=0.2).[94]
No grade ¾ mucositis was seen with uproleselan and 7+3.