IDH1/2-inhibitor–based treatments and responses (clinical and molecular) of patients with IDH1/2-mutated post–MPN AML (N = 12)
| Pt* . | IDH1/2-inhibitor–based treatment . | Clinical trial (NCT ID)† . | IDH1/2 VAF prior to IDH1/2-i Rx (%) . | IDH1/2 VAF after IDH1/2-i Rx (%) . | Response‡ . | BM blasts, prior to and during IDH1/2-i Rx . |
|---|---|---|---|---|---|---|
| 1 | ENASIDENIB + RUX + AZA | — | IDH2 R140Q (47) | IDH2 clearance§ | CR | 45% → 1%, MRD negative |
| 2 | AG-120 + VENETOCLAX | NCT03471260 | IDH1 R132C (21) | IDH1 clearance§ | CR | 26% → 1%, MRD 0.18% |
| 3 | AG-221 + [7+3] | NCT02632708 | IDH2 R140Q (<3) | IDH2 clearance§ | CR | 25% → 1%, MRD 0.3% |
| 4 | FT-2102 + AZA | NCT02719574 | IDH1 R132C (44) | IDH1 R132C (36) | SD | 86% →7%, MRD 0.06% |
| IDH2 R140Q (2) | ||||||
| 5 | AG-221 + AZA | NCT02677922 | IDH2 R140Q (16) | IDH2 clearance§ | SD | 79% → 9% |
| 6 | ENASIDENIB‖ + RUX + DAC | — | IDH2 R140Q (35) | NA | NR | NA |
| 7 | AG-120¶ | NCT02074839 | IDH1 R132C (20) | NA | NR | NA |
| 8 | Investigational IDH1-i | NCT03127735 | IDH1 R132C (40) | IDH1 R132C (45.5) | SD | 69% → 7% |
| AG-120 + VENETOCLAX | NCT03471260 | IDH1 R132F (<5) | ||||
| IVOSIDENIB + VEN + AZA | — | IDH2 R140Q (38.5) | ||||
| 9 | IDH-305 | NCT02381886 | IDH1 R132C (11) | IDH1 R132C# | SD | 64% → 15% |
| 10 | AG-120 | NCT02074839 | IDH1 R132C (8.5) | IDH1 R132C (42) | SD | 54% → 13% |
| 11 | AG-221 | NCT01915498 | IDH2 R140Q (28) | IDH2 R140Q# | NR | No change |
| 12 | FT-2102 | NCT02719574 | IDH1 R132H (25) | IDH1 R132H# | PD | 12% → 88% |
| IVOSIDENIB + CLIA + GO | — |
| Pt* . | IDH1/2-inhibitor–based treatment . | Clinical trial (NCT ID)† . | IDH1/2 VAF prior to IDH1/2-i Rx (%) . | IDH1/2 VAF after IDH1/2-i Rx (%) . | Response‡ . | BM blasts, prior to and during IDH1/2-i Rx . |
|---|---|---|---|---|---|---|
| 1 | ENASIDENIB + RUX + AZA | — | IDH2 R140Q (47) | IDH2 clearance§ | CR | 45% → 1%, MRD negative |
| 2 | AG-120 + VENETOCLAX | NCT03471260 | IDH1 R132C (21) | IDH1 clearance§ | CR | 26% → 1%, MRD 0.18% |
| 3 | AG-221 + [7+3] | NCT02632708 | IDH2 R140Q (<3) | IDH2 clearance§ | CR | 25% → 1%, MRD 0.3% |
| 4 | FT-2102 + AZA | NCT02719574 | IDH1 R132C (44) | IDH1 R132C (36) | SD | 86% →7%, MRD 0.06% |
| IDH2 R140Q (2) | ||||||
| 5 | AG-221 + AZA | NCT02677922 | IDH2 R140Q (16) | IDH2 clearance§ | SD | 79% → 9% |
| 6 | ENASIDENIB‖ + RUX + DAC | — | IDH2 R140Q (35) | NA | NR | NA |
| 7 | AG-120¶ | NCT02074839 | IDH1 R132C (20) | NA | NR | NA |
| 8 | Investigational IDH1-i | NCT03127735 | IDH1 R132C (40) | IDH1 R132C (45.5) | SD | 69% → 7% |
| AG-120 + VENETOCLAX | NCT03471260 | IDH1 R132F (<5) | ||||
| IVOSIDENIB + VEN + AZA | — | IDH2 R140Q (38.5) | ||||
| 9 | IDH-305 | NCT02381886 | IDH1 R132C (11) | IDH1 R132C# | SD | 64% → 15% |
| 10 | AG-120 | NCT02074839 | IDH1 R132C (8.5) | IDH1 R132C (42) | SD | 54% → 13% |
| 11 | AG-221 | NCT01915498 | IDH2 R140Q (28) | IDH2 R140Q# | NR | No change |
| 12 | FT-2102 | NCT02719574 | IDH1 R132H (25) | IDH1 R132H# | PD | 12% → 88% |
| IVOSIDENIB + CLIA + GO | — |
BM, bone marrow; IDH1/2-i, IDH1/2 inhibitor; IDH1-i, IDH1 inhibitor; MRD, measurable residual disease (measured by flow cytometry); NA, not analyzed; NR, no response; PD, progressive disease.
Patients 1 through 7 had newly diagnosed post–MPN AML, and patients 8 through 12 had R/R post–MPN AML.
Clinical trial identifiers are reported with NCT numbers; the remaining treatments were off clinical trials.
Responses were assessed according to the 2017 ELN criteria.15
IDH1/2 clearance is defined as undetectable VAF (measured by NGS).
Enasidenib was added to the regimen towards the end of post-MPN AML treatment; however, patient 6 harbored IDH2 for several months (during MF-AP).
Patient 7 harbored IDH1 for several months (during MF-AP) prior to treatment with AG-120.
Positive IDH1/2 mutation; VAF not reported.