Patient characteristics
| Age/sex . | FLT3 mutation . | Other mutations . | CNS status . | Upfront chemotherapy regimen . | Time from diagnosis to first relapse, mo . | Gilteritinib regimen (line of therapy) . | Gilteritinib dosing schedule . | Cycles . | Response to gilteritinib and cycle of MRD . | Toxicity . | Status . | Follow-up, mo . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 6/M | FLT3 non-ITD p.N676K missense variant of TKD | RUNX1, GATA2, CREBBP | CNS3 | ADE + GO | Refractory | FLAG-Ida + gilteritinib | 40 mg (2 mg/kg) daily d 1-14 | 1 | NR | Alanine aminotransferase increased, febrile neutropenia, creatinine elevation, seizure, anemia, thrombocytopenia | Alive | 7 |
| 21/F | FLT3 ITD, ITD ratio of 0.27 | NPM1 | CNS1 | CLIA + VEN | NA | CLIA + gilteritinib consolidation | 80 mg daily | 4 | CR; MRD− first cycle | Febrile neutropenia, constipation, abdominal pain, dysuria, bacteremia, acidosis, anemia, thrombocytopenia | Alive | 10 |
| 21/F | FLT3-ITD, ITD ratio of 0.10 | NPM1 | CNS1 | 7 + 3 and midostaurin | Refractory | CLIA + VEN + gilteritinib | 120 mg daily ×14 d/cycle ×2 cycles; 40 mg daily post-SCT maintenance ×3 mo and then increased to 80 mg daily | 3, then post-SCT maintenance | CR; MRD− third cycle | Febrile neutropenia, anemia, thrombocytopenia, bacteremia, colitis, HTN | Alive | 14 |
| 17/F | FLT3 ITD, ITD ratio of 0.02 | Negative | CNS1 | ADE + sorafenib | Refractory | Cytarabine + GO + gilteritinib | 120 mg daily ×1 cycle; post-SCT maintenance 40, 80, 120 mg daily (adjusted because of AEs) | 5, then post-SCT maintenance | CR; MRD− after SCT | Febrile neutropenia, nausea, hypomagnesemia, neuropathy, thrombocytopenia, anemia, paresthesia, rhabdomyolysis, lung infection | Alive | 18 |
| 19/M | FLT3 ITD and D835 point mutation; ITD ratio of 0.625 and D835 ratio of 0.062 | Mosaic germ line GATA2 deletion, KIT | CNS3 | ADE | Refractory | (1) Mitoxantrone + cytarabine; (2) AZA, fludarabine, cytarabine; (3) DAC; (4) AMG330 (BiTE CD33/CD3); (5) CAR T-cell infusion; (6) Ox40 mAb; (7) S64315 (MCL-1 inhibitor); (8) DAC + VEN + midostaurin; (9) DCLL9718S (anti-CLL1) + AZA; (10) DAC + VEN + sorafenib; (10) DAC + VEN + gilteritinib + ponatinib; (11) fludarabine + cytarabine + vorinostat + ponatinib + gilteritinib | 120 mg daily | 7 | NR | Alanine aminotransferase increased, febrile neutropenia, fungal pneumonia, bacteremia, intracranial hemorrhage, acidosis | Dead | 8 |
| 20/F | FLT3-ITD then FLT3-TKD (ratios unknown) | CUX1, WT1 | CNS1 | ADE + sorafenib | 27 mo; day +700 from SCT | (1) FLAG + midostaurin; (2) cytarabine + mitoxantrone + midostaurin; (3) second SCT; (4) DAC + vorinostat + sunitinib; (5) DAC + VEN + sunitinib; (6) DAC + sunitinib + AZA + gilteritinib + VEN | 120 mg daily continuous | 1 | NR | Febrile neutropenia, anemia, thrombocytopenia | Dead | 2 |
| 19/F | FLT3 ITD, ITD ratio of 0.46 | NPM1, TP53, WT1 | CNS1 | ADE + sorafenib | 10 mo | (1) CPX-351 + FLAG; (2) cytarabine + PEG + midostaurin; (2) DAC + VEN + sorafenib; (3) SCT + post-SCT maintenance with sorafenib; (4) azacitidine + VEN + gilteritinib; (5) second SCT + post-SCT maintenance AZA + gilteritinib | 80 mg daily continuous | 3, then post-SCT maintenance | CR; MRD− third cycle | Febrile neutropenia, anemia, bacteremia, neuropathy, thrombocytopenia, hypomagnesemia, thromboembolic event, paresthesia, alanine aminotransferase increased, creatinine increase | Alive | 12 |
| 14/M | FLT3-ITD allelic ratio of 0.67 (N609_L610ins) | NUP98-NSD1, WT1 S118fs*81 | CNS1 | ADE | Refractory | AZA-FLA + gilteritinib ×2 cycles, HSCT, post-HSCT gilteritinib | AZA-FLA + gilteritinib ×2 cycles, HSCT, post-HSCT gilteritinib | 2, then post-SCT maintenance | CR; MRD− first cycle | Tooth discoloration, febrile neutropenia with S mitis bacteremia, anemia, thrombocytopenia | Alive | 7 |
| Age/sex . | FLT3 mutation . | Other mutations . | CNS status . | Upfront chemotherapy regimen . | Time from diagnosis to first relapse, mo . | Gilteritinib regimen (line of therapy) . | Gilteritinib dosing schedule . | Cycles . | Response to gilteritinib and cycle of MRD . | Toxicity . | Status . | Follow-up, mo . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 6/M | FLT3 non-ITD p.N676K missense variant of TKD | RUNX1, GATA2, CREBBP | CNS3 | ADE + GO | Refractory | FLAG-Ida + gilteritinib | 40 mg (2 mg/kg) daily d 1-14 | 1 | NR | Alanine aminotransferase increased, febrile neutropenia, creatinine elevation, seizure, anemia, thrombocytopenia | Alive | 7 |
| 21/F | FLT3 ITD, ITD ratio of 0.27 | NPM1 | CNS1 | CLIA + VEN | NA | CLIA + gilteritinib consolidation | 80 mg daily | 4 | CR; MRD− first cycle | Febrile neutropenia, constipation, abdominal pain, dysuria, bacteremia, acidosis, anemia, thrombocytopenia | Alive | 10 |
| 21/F | FLT3-ITD, ITD ratio of 0.10 | NPM1 | CNS1 | 7 + 3 and midostaurin | Refractory | CLIA + VEN + gilteritinib | 120 mg daily ×14 d/cycle ×2 cycles; 40 mg daily post-SCT maintenance ×3 mo and then increased to 80 mg daily | 3, then post-SCT maintenance | CR; MRD− third cycle | Febrile neutropenia, anemia, thrombocytopenia, bacteremia, colitis, HTN | Alive | 14 |
| 17/F | FLT3 ITD, ITD ratio of 0.02 | Negative | CNS1 | ADE + sorafenib | Refractory | Cytarabine + GO + gilteritinib | 120 mg daily ×1 cycle; post-SCT maintenance 40, 80, 120 mg daily (adjusted because of AEs) | 5, then post-SCT maintenance | CR; MRD− after SCT | Febrile neutropenia, nausea, hypomagnesemia, neuropathy, thrombocytopenia, anemia, paresthesia, rhabdomyolysis, lung infection | Alive | 18 |
| 19/M | FLT3 ITD and D835 point mutation; ITD ratio of 0.625 and D835 ratio of 0.062 | Mosaic germ line GATA2 deletion, KIT | CNS3 | ADE | Refractory | (1) Mitoxantrone + cytarabine; (2) AZA, fludarabine, cytarabine; (3) DAC; (4) AMG330 (BiTE CD33/CD3); (5) CAR T-cell infusion; (6) Ox40 mAb; (7) S64315 (MCL-1 inhibitor); (8) DAC + VEN + midostaurin; (9) DCLL9718S (anti-CLL1) + AZA; (10) DAC + VEN + sorafenib; (10) DAC + VEN + gilteritinib + ponatinib; (11) fludarabine + cytarabine + vorinostat + ponatinib + gilteritinib | 120 mg daily | 7 | NR | Alanine aminotransferase increased, febrile neutropenia, fungal pneumonia, bacteremia, intracranial hemorrhage, acidosis | Dead | 8 |
| 20/F | FLT3-ITD then FLT3-TKD (ratios unknown) | CUX1, WT1 | CNS1 | ADE + sorafenib | 27 mo; day +700 from SCT | (1) FLAG + midostaurin; (2) cytarabine + mitoxantrone + midostaurin; (3) second SCT; (4) DAC + vorinostat + sunitinib; (5) DAC + VEN + sunitinib; (6) DAC + sunitinib + AZA + gilteritinib + VEN | 120 mg daily continuous | 1 | NR | Febrile neutropenia, anemia, thrombocytopenia | Dead | 2 |
| 19/F | FLT3 ITD, ITD ratio of 0.46 | NPM1, TP53, WT1 | CNS1 | ADE + sorafenib | 10 mo | (1) CPX-351 + FLAG; (2) cytarabine + PEG + midostaurin; (2) DAC + VEN + sorafenib; (3) SCT + post-SCT maintenance with sorafenib; (4) azacitidine + VEN + gilteritinib; (5) second SCT + post-SCT maintenance AZA + gilteritinib | 80 mg daily continuous | 3, then post-SCT maintenance | CR; MRD− third cycle | Febrile neutropenia, anemia, bacteremia, neuropathy, thrombocytopenia, hypomagnesemia, thromboembolic event, paresthesia, alanine aminotransferase increased, creatinine increase | Alive | 12 |
| 14/M | FLT3-ITD allelic ratio of 0.67 (N609_L610ins) | NUP98-NSD1, WT1 S118fs*81 | CNS1 | ADE | Refractory | AZA-FLA + gilteritinib ×2 cycles, HSCT, post-HSCT gilteritinib | AZA-FLA + gilteritinib ×2 cycles, HSCT, post-HSCT gilteritinib | 2, then post-SCT maintenance | CR; MRD− first cycle | Tooth discoloration, febrile neutropenia with S mitis bacteremia, anemia, thrombocytopenia | Alive | 7 |
ADE, cytarabine, daunorubicin, etoposide; AZA, azacitidine; BiTE, bispecific T-cell engager; CAR, chimeric antigen receptor; CLIA, cladribine, idarubicin, cytarabine; CNS, central nervous system; CR, complete response; DAC, decitabine; FLAG, fludarabine, cytarabine, granulocyte colony-stimulating factor; GO, gemtuzumab ozogamicin; HSCT, hematopoietic stem cell transplantation; HTN, hypertension; Ida, idarubicin; mAb, monoclonal antibody; MRD, minimal residual disease; NA, not applicable; NR, no response; PEG, pegaspargase; SCT, stem cell transplantation; TKD, tyrosine kinase domain; VEN, venetoclax.