Table 1.
AML mutations selectively targeted by drugs, and available studies in post-transplant maintenance and relapse
| Mutated gene | Drug | Trials for maintenance after alloHCT | Trials in relapsed AML |
|---|---|---|---|
| FLT3 | Midostaurin | 120 pts randomized to midostaurin vs standard of care. OS 85% vs 76% at 24 months (P = 0.34). NCT018833624 | 99 pts treated. ORR 71% in FLT3mut pts and 42% in FLT3wt pts. NCT000459429 |
| Sorafenib (active only in FLT3-ITD) | 83 pts randomized to sorafenib vs placebo. OS 90.5% vs 66.2% at 24 months (P = 0.007). DRKS000005915 202 pts randomized to sorafenib vs placebo. 2-year OS 82% vs 68% (P = 0.012). NCT024742906 |
29 pts treated. ORR 37, 9%, median OS 7.1 months.10 | |
| Crenolanib | A phase 2 trial is currently ongoing. NCT02400255 | 38 pts treated; ORR 47% at 14 weeks.11 | |
| Gilteritinib | 356 pts randomized to gilteritinib vs placebo. No difference in OS, but in pts with MRD higher RFS with gilteritinib (P = 0.0065). NCT029972027 | 371 pts randomized to gilteritinib vs chemotherapy. ORR 67.6% vs 25.8%, OS 9.3 months vs 5.6 months (P < 0.001). NCT0242193912 | |
| Quizartinib (active only in FLT3-ITD) | 13 pts treated, acceptable toxicities, OS 13-142 weeks; no difference in OS vs historical cohort. NCT014684678 | 367 pts randomized to quizartinib vs chemotherapy. OS 6.2 months vs 4.7 months (P = 0.02). NCT02039726 (Cortes et al.)13 | |
| IDH1 | Ivosidenib | 16 pts treated, PFS 81% at 2 years, OS 88% at 2 years. NCT0356482115 | 258 pts treated. ORR 41.6%. NCT0207483918 |
| Olutasidenib | 31 pts treated. ORR 22%. NCT0271957416 | ||
| IDH2 | Enasidenib | 19 pts treated, PFS 69% at 2 years, OS 74% at 2 years. NCT0351551214 | 229 pts treated. ORR 40.3%. NCT0191549817 |
| KMT2A fusion NPM1 NUP98 fusion |
Revumenib | 9 pts treated, CR maintained in 6/9 (66%). NCT0406539919 | 68 pts treated. ORR 53%, CR/CRh 30%. NCT0406539920 |
| JNJ-72576617 | A phase 1 trial is currently ongoing. NCT05453903 | ||
| Ziftomenib | A phase 1 trial is currently ongoing. NCT06440135 | A phase 1 trial is currently ongoing. NCT04067336 |
CR, complete remission; CRh, complete remission with partial hematological recovery; mut, mutated; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; pts, patients; RFS, relapse-free survival; wt, wild type.