Recently approved drugs for AML
| Drug . | Indication . | Route of administration . | Significant findings in clinical trials . | Issues needing special attention . |
|---|---|---|---|---|
| Midostaurin Rydapt® | Newly diagnosed FLT3 mut AML in combination with intensive therapy (FDA, EMA) | Oral | Phase 3 trial (RATIFY): intensive chemotherapy + midostaurin vs placebo: 4-year OS: 51.4% midostaurin vs 44.3% placebo | Careful administration of comedications with strong CYP3A4 inhibitory activity |
| CPX-351 Vyxeos® | Newly diagnosed tAML, AML-MRC (FDA, EMA) | IV | Phase 3 trial: median OS 9.6 (CPX-351) vs 6.0 months (standard chemotherapy) | Side effects similar to standard chemotherapy but less alopecia |
| Gemtuzumab ozogamicin Mylotarg® | Newly diagnosed CD33+ AML (FDA, EMA) in combination with intensive therapy, R/R CD33+ AML in combination with intensive therapy (FDA) | IV | Phase 3 trial (ALFA-0701): intensive chemotherapy +/− GO: 2-year OS: 53.2% GO vs 41.9% standard | Hepatotoxicity (including veno-occlusive disease), infusion-related reactions, infection |
| Venetoclax Venclexta® | Newly diagnosed AML in patients ≥75 years or with comorbidities precluding intensive therapy; in combination with LDAC or HMA (FDA) | Oral | VIALE-A trial: VEN-AZA vs placebo: median OS 14.7 (venetoclax) vs 9.6 months (placebo) VIALE-C trial: LDAC-VEN vs placebo: median OS 8.4 (venetoclax) vs 4.1 months (placebo) | Hematological toxicity (follow recommended dose adjustments), neutropenic fever, dose adjustments if comedications with strong CYP3A4 inhibitory activity, tumor lysis syndrome (but much rarer than in CLL) |
| Glasdegib Daurismo® | Newly diagnosed AML in patients ≥75 years or with comorbidities precluding intensive therapy; in combination with LDAC (FDA, EMA) | Oral | Phase 2 BRIGHT AML 1003 trial: LDAC +/− glasdegib: median OS was 8.8 (LDAC-glasdegib) vs 4.9 months (LDAC alone) | Musculoskeletal pain |
| CC-486 Onureg® | Maintenance therapy AML patients in CR/CRi after intensive induction who are unable to complete intensive curative therapy | Oral | Phase 3 QUAZAR AML-001: CC-486 vs placebo: median OS 24.7 (CC-486) vs 14.8 months (placebo) | GI toxicity, neutropenia |
| Enasidenib Idhifa® | R/R IDH2 mut AML as monotherapy (FDA) | Oral | Phase 1/2 trial: OR in 40.3% of patients, OS 9.3 months | Check IDH2 mutational status at time of R/R disease, IDH differentiation syndrome, indirect hyperbilirubinemia |
| Ivosidenib Tibsovo® | Newly diagnosed or R/R IDH1 mut AML as monotherapy(FDA) | Oral | Phase 1b: monotherapy CR in 22% and OR in 42% of patients | Check IDH1 mutational status at time of diagnosis and R/R disease, IDH differentiation syndrome, indirect hyperbilirubinemia |
| Gilteritinib Xospata® | R/R FLT3 mut AML as monotherapy (FDA, EMA) | Oral | Phase 3 (ADMIRAL) trial: gilteritinib vs salvage chemotherapy: CR/CRi 34% (gilteritinib) vs 15.4% (salvage therapy); OS 9.3 (gilteritinib) vs 5.6 months (salvage therapy) | Check FLT3 mutational status at time of R/R disease |
| Drug . | Indication . | Route of administration . | Significant findings in clinical trials . | Issues needing special attention . |
|---|---|---|---|---|
| Midostaurin Rydapt® | Newly diagnosed FLT3 mut AML in combination with intensive therapy (FDA, EMA) | Oral | Phase 3 trial (RATIFY): intensive chemotherapy + midostaurin vs placebo: 4-year OS: 51.4% midostaurin vs 44.3% placebo | Careful administration of comedications with strong CYP3A4 inhibitory activity |
| CPX-351 Vyxeos® | Newly diagnosed tAML, AML-MRC (FDA, EMA) | IV | Phase 3 trial: median OS 9.6 (CPX-351) vs 6.0 months (standard chemotherapy) | Side effects similar to standard chemotherapy but less alopecia |
| Gemtuzumab ozogamicin Mylotarg® | Newly diagnosed CD33+ AML (FDA, EMA) in combination with intensive therapy, R/R CD33+ AML in combination with intensive therapy (FDA) | IV | Phase 3 trial (ALFA-0701): intensive chemotherapy +/− GO: 2-year OS: 53.2% GO vs 41.9% standard | Hepatotoxicity (including veno-occlusive disease), infusion-related reactions, infection |
| Venetoclax Venclexta® | Newly diagnosed AML in patients ≥75 years or with comorbidities precluding intensive therapy; in combination with LDAC or HMA (FDA) | Oral | VIALE-A trial: VEN-AZA vs placebo: median OS 14.7 (venetoclax) vs 9.6 months (placebo) VIALE-C trial: LDAC-VEN vs placebo: median OS 8.4 (venetoclax) vs 4.1 months (placebo) | Hematological toxicity (follow recommended dose adjustments), neutropenic fever, dose adjustments if comedications with strong CYP3A4 inhibitory activity, tumor lysis syndrome (but much rarer than in CLL) |
| Glasdegib Daurismo® | Newly diagnosed AML in patients ≥75 years or with comorbidities precluding intensive therapy; in combination with LDAC (FDA, EMA) | Oral | Phase 2 BRIGHT AML 1003 trial: LDAC +/− glasdegib: median OS was 8.8 (LDAC-glasdegib) vs 4.9 months (LDAC alone) | Musculoskeletal pain |
| CC-486 Onureg® | Maintenance therapy AML patients in CR/CRi after intensive induction who are unable to complete intensive curative therapy | Oral | Phase 3 QUAZAR AML-001: CC-486 vs placebo: median OS 24.7 (CC-486) vs 14.8 months (placebo) | GI toxicity, neutropenia |
| Enasidenib Idhifa® | R/R IDH2 mut AML as monotherapy (FDA) | Oral | Phase 1/2 trial: OR in 40.3% of patients, OS 9.3 months | Check IDH2 mutational status at time of R/R disease, IDH differentiation syndrome, indirect hyperbilirubinemia |
| Ivosidenib Tibsovo® | Newly diagnosed or R/R IDH1 mut AML as monotherapy(FDA) | Oral | Phase 1b: monotherapy CR in 22% and OR in 42% of patients | Check IDH1 mutational status at time of diagnosis and R/R disease, IDH differentiation syndrome, indirect hyperbilirubinemia |
| Gilteritinib Xospata® | R/R FLT3 mut AML as monotherapy (FDA, EMA) | Oral | Phase 3 (ADMIRAL) trial: gilteritinib vs salvage chemotherapy: CR/CRi 34% (gilteritinib) vs 15.4% (salvage therapy); OS 9.3 (gilteritinib) vs 5.6 months (salvage therapy) | Check FLT3 mutational status at time of R/R disease |
CLL, chronic lymphocytic leukemia; CRi, CR with incomplete hematologic recovery; IV, intravenous; mut, mutated; OR, overall response.