FLT3 KD mutations found at relapse in patients with bone marrow responses on quizartinib
| Patients number . | Sex . | Age (y) . | Prior therapy . | Karyotype pretreatment . | Karyotype at relapse . | Bone marrow blasts in relapse sample (%) . | Quizartinib dose (mg) . | Bone marrow blasts at best response (%) . | FLT3 KD mutation at relapse . | Mutation detection method . | Weeks on study . |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 1009-003 | F | 75 | 7+3 | 45∼54,XX,+3,+6,+7,+8,+13,+14,+21,+22[cp15]/46,XX[5] | 52,XX,+3,+6,+7,+8,+10,+12,+13[cp7]/46,XX[14] | 90 | 90, increased to 135 for refractory disease | <5 | D835F, D835Y, D835V | SMRT sequencing | 12 |
| 1009-007 | F | 64 | 7+3, HiDAC | Normal | ND | 75 | 90, reduced to 60 for QT prolongation | <5 | D835Y | SMRT sequencing | 10 |
| 1009-014 | M | 62 | 7+3, HAM | Normal | ND | 10-15 | 135, reduced to 90 for QT prolongation | <5 | D835V | PCR subcloning | 10 |
| 1009-018 | M | 70 | 7+3, HiDAC | 45,X,-Y,add(2)(p12),t(6;19)(p21;q11.2),t(8;21)(q22;q22),add(16)(q13),add(20)(q?13.1)[20] | 45,X,-Y, add(2)(p12), t(6;19)(p21;q11.2), t(8;21)(q22;q22), add(16)(q13), add(20)(q?13.1)[3]/46, XY[2] | 38 | 135, reduced to 90 for QT prolongation | <5 | None | PCR subcloning | 15 |
| 1009-019 | M | 52 | 7+3, HiDAC, Cytoxan/TBI | 46, XY, add(6)(p21),del(8)(p21),add(12)(q24.1)[13]/46,XY,del(1)(q32),del(7)(q22q32),der(6;12)(q10;p10),add(22)(q?11.2),+mar[3]/45,XY,t(1;2)(p?22;q11.2)-21[1]/46,XY[3] | ND | 68 | 135 | <5 | D835Y | PCR subcloning | 10 |
| 1009-021 | M | 65 | Azacitidine + sapacitabine | 46,XY,+11[15] | 46,XY,+11[13]/47,sl,add(17)(p11.2)[9] | 45 | 135 | 10 | D835Y | PCR subcloning | 18 |
| 3351-1085 | F | 69 | Clofarabine, MEC | Normal | No growth, most recent karyotype during response: 46,XX,t(8;12)(q12;p13),add(10)(q11,2),-11,+mar[5]/46,XX[15] | 78 | 30, increased to 60 for refractory disease | <5 | D835Y | PCR subcloning | 11 |
| 1011-006 | M | 70 | 7+3, low-dose cytarabine | Normal | ND | 10 | 200 | 5 | D835Y | SMRT sequencing | 7 |
| 1011-007 | F | 56 | 7+3, HAM | Normal | 46,XX,del(11)(p?13p?15)[12]/46,XX[9] | 80 | 200 | <5 | F691L, D835V, D835Y | SMRT sequencing | 8 |
| 1005-004 | F | 60 | Cytarabine and mitoxantrone | Normal | Normal | 92 | 200 | <5 | F691L | SMRT sequencing | 19 |
| 1005-006 | M | 43 | 7+3, MEC | 46,XY,t(1;15)(p22;q15) | ND | 59 | 200 | <5 | D835Y, D835F | SMRT sequencing | 6 |
| 1005-007 | F | 59 | 7+3, HiDAC | Normal | ND | 39 | 135 | <5 | D835V, D835Y | SMRT sequencing | 23 |
| 1005-009 | M | 68 | Cytarabine and mitoxantrone | Normal | ND | 58 | 135 | <5 | D835Y | SMRT sequencing | 18 |
| 1005-010 | M | 52 | 7+3, HiDAC, mitoxantrone, and etoposide | 46,XY,t(4;12)(q26;p11.2),t(8;14)(q13;q11.2) | ND | 22 | 135 | <5 | F691L | SMRT sequencing | 19 |
| 512-92-61 (0820-1039) | F | 64 | 7+3, carboplatin and topotecan | Normal | 46,XX,t(5;7)(q15;p15)[2]/46,XX[18] | 80 | 30, increased to 60 for refractory disease | <5 | D835I | PCR subcloning | 8 |
| 1009-011* | F | 33 | 7+3, HiDAC, G-CLAC | Normal | NA | <5 | 90 | <5 | NA | NA | Off study for transplant after 6 weeks |
| Patients number . | Sex . | Age (y) . | Prior therapy . | Karyotype pretreatment . | Karyotype at relapse . | Bone marrow blasts in relapse sample (%) . | Quizartinib dose (mg) . | Bone marrow blasts at best response (%) . | FLT3 KD mutation at relapse . | Mutation detection method . | Weeks on study . |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 1009-003 | F | 75 | 7+3 | 45∼54,XX,+3,+6,+7,+8,+13,+14,+21,+22[cp15]/46,XX[5] | 52,XX,+3,+6,+7,+8,+10,+12,+13[cp7]/46,XX[14] | 90 | 90, increased to 135 for refractory disease | <5 | D835F, D835Y, D835V | SMRT sequencing | 12 |
| 1009-007 | F | 64 | 7+3, HiDAC | Normal | ND | 75 | 90, reduced to 60 for QT prolongation | <5 | D835Y | SMRT sequencing | 10 |
| 1009-014 | M | 62 | 7+3, HAM | Normal | ND | 10-15 | 135, reduced to 90 for QT prolongation | <5 | D835V | PCR subcloning | 10 |
| 1009-018 | M | 70 | 7+3, HiDAC | 45,X,-Y,add(2)(p12),t(6;19)(p21;q11.2),t(8;21)(q22;q22),add(16)(q13),add(20)(q?13.1)[20] | 45,X,-Y, add(2)(p12), t(6;19)(p21;q11.2), t(8;21)(q22;q22), add(16)(q13), add(20)(q?13.1)[3]/46, XY[2] | 38 | 135, reduced to 90 for QT prolongation | <5 | None | PCR subcloning | 15 |
| 1009-019 | M | 52 | 7+3, HiDAC, Cytoxan/TBI | 46, XY, add(6)(p21),del(8)(p21),add(12)(q24.1)[13]/46,XY,del(1)(q32),del(7)(q22q32),der(6;12)(q10;p10),add(22)(q?11.2),+mar[3]/45,XY,t(1;2)(p?22;q11.2)-21[1]/46,XY[3] | ND | 68 | 135 | <5 | D835Y | PCR subcloning | 10 |
| 1009-021 | M | 65 | Azacitidine + sapacitabine | 46,XY,+11[15] | 46,XY,+11[13]/47,sl,add(17)(p11.2)[9] | 45 | 135 | 10 | D835Y | PCR subcloning | 18 |
| 3351-1085 | F | 69 | Clofarabine, MEC | Normal | No growth, most recent karyotype during response: 46,XX,t(8;12)(q12;p13),add(10)(q11,2),-11,+mar[5]/46,XX[15] | 78 | 30, increased to 60 for refractory disease | <5 | D835Y | PCR subcloning | 11 |
| 1011-006 | M | 70 | 7+3, low-dose cytarabine | Normal | ND | 10 | 200 | 5 | D835Y | SMRT sequencing | 7 |
| 1011-007 | F | 56 | 7+3, HAM | Normal | 46,XX,del(11)(p?13p?15)[12]/46,XX[9] | 80 | 200 | <5 | F691L, D835V, D835Y | SMRT sequencing | 8 |
| 1005-004 | F | 60 | Cytarabine and mitoxantrone | Normal | Normal | 92 | 200 | <5 | F691L | SMRT sequencing | 19 |
| 1005-006 | M | 43 | 7+3, MEC | 46,XY,t(1;15)(p22;q15) | ND | 59 | 200 | <5 | D835Y, D835F | SMRT sequencing | 6 |
| 1005-007 | F | 59 | 7+3, HiDAC | Normal | ND | 39 | 135 | <5 | D835V, D835Y | SMRT sequencing | 23 |
| 1005-009 | M | 68 | Cytarabine and mitoxantrone | Normal | ND | 58 | 135 | <5 | D835Y | SMRT sequencing | 18 |
| 1005-010 | M | 52 | 7+3, HiDAC, mitoxantrone, and etoposide | 46,XY,t(4;12)(q26;p11.2),t(8;14)(q13;q11.2) | ND | 22 | 135 | <5 | F691L | SMRT sequencing | 19 |
| 512-92-61 (0820-1039) | F | 64 | 7+3, carboplatin and topotecan | Normal | 46,XX,t(5;7)(q15;p15)[2]/46,XX[18] | 80 | 30, increased to 60 for refractory disease | <5 | D835I | PCR subcloning | 8 |
| 1009-011* | F | 33 | 7+3, HiDAC, G-CLAC | Normal | NA | <5 | 90 | <5 | NA | NA | Off study for transplant after 6 weeks |
F, female; G-CLAC, G-CSF clofarabine high-dose cytarabine (Ara-C); HAM, high-dose Ara-C mitoxantrone; HiDAC, high-dose Ara-C; M, male; MEC, mitoxantrone etoposide cytarabine (Ara-C); NA, not applicable; ND, not done; QT, QT interval; SMRT, single-molecule real-time [sequencing]; TBI, total body irradiation.
Patient did not relapse on study drug; no relapse sample sequenced.