Table 2.
Main evidence of in vivo GO efficacy in AML subgroups defined according to biomarkers of response.
| Biomarker | Main Observations | Study | References |
|---|---|---|---|
| CD33 expression | GO improved OS of patients with >80% CD33+ blasts | EORTC-GIMEMA AML-19 | [37] |
| GO improved EFS and RFS of patients expressing high CD33 surface levels | ALFA-0701 | [80] | |
| Low percentage of CD33+ blasts associated with higher risk of relapse after GO | MRC AML15, NCRI AML16 | [81] | |
| Patients in the 2nd to 4th quartiles of CD33 surface expression had higher CR and lower MRD rates at the end of the first cycle, lower risk of relapse and better DFS | COG AAML0531 | [76] | |
| CD33 SNPs | rs12459419 CC genotype: lower risk of relapse and better EFS and DFS in the GO arm | COG AAML0531 | [82] |
| rs12459419 C > T SNP: no GO benefit | COG AAML0531 | [82] | |
| NPM1-mut patients with the rs12459419 CC genotype showed a superior RFS in the GO arm | AMLSG 09-09 | [83] | |
| Patients carrying rs1803254 GG, rs35112940 GG, rs2455069 GG, rs1736475 TT and rs201074739 CCGG/CCGG had reduced RR to GO | COG AAML0531 | [88] | |
| CD33_PGx6_Score >0 associated with high CD33 expression, better RFS and lower RR in the GO arm | COG AAML0531 | [88] | |
| Cytogenetic alterations | GO provided a survival benefit in patients with good and intermediate cytogenetic risks, but not in the adverse cytogenetic group | Various | [37,43,47,52,89,91] |
| The addition of GO to standard chemotherapy reduced the risk of relapse in CBF cases carrying KIT mutations | FLAG-GO | [93] | |
| The addition of GO to standard chemotherapy induced higher EFS in KMT2A-rearranged AML | COG AAML0531 | [100] | |
| Molecular profile | GO provided a survival benefit in patients from favorable and intermediate, but not adverse molecular risk categories (ELN 2017) | ALFA-0701 | [49,91] |
| GO provided EFS, RFS and OS benefit in NPM1-mut AML and reduced the incidence of relapse in NPM1-mut patients achieving CR/CRi | ALFA-0701, AMLSG 09-09 | [50,107] | |
| GO improved EFS of FLT3-ITD-wt, but not FLT3-ITD-mut patients | AMLSG 09-09, MRC AML15, NCRI AML16 | [52,107] | |
| GO improved OS, EFS and RFS and reduced the RR in adult FLT3-ITD-mut patients | COG AAML03P1, COG AAML0531 | [50,92,107,108] | |
| GO provided clinical benefit to patients with activating signaling mutations | ALFA-0701 | [104] | |
| The mutational status of seven genes identified a group characterized by NPM1-mut, FLT3-ITD-wt or biallelic CEBPA-mut that displayed the best outcome in the GO arm | GOELAMS/FILO AML 2006-IR | [112] | |
| Multidrug resistance | ABCB1 expression associated with failure to clear bone marrow blasts and to achieve CR or poos OS and EFS | Various | [115,118,119,121,122,123,124,125] |
| ABCB1 rs1045642 CT or TT genotype associated with better outcomes in GO recipients | COG AAML0531 | [123] | |
| MRD | GO-treated patients frequently achieved negativity for NPM1 mutation MRD and a reduction 1000 of NPM1 mutation transcript combined with MRD negativity was predictive of lower RR | ALFA-0701, AMLSG 09-09 | [130,131] |
| LSC signature | GO addition improved the outcome of patients having low LSC17 score but not those with high signature score | ALFA-0701 | [132] |
CR: complete remission; CRi: complete remission with incomplete hematologic recovery; DFS: disease free survival; EFS: event free survival; LSC: leukemia stem cell; MRD: minimal residual disease; mut: mutated; OS: overall survival; RFS; relapse free survival; RR: relapse rate; SNP: single nucleotide polymorphism.