S126: Gemtuzumab-Based Induction Chemotherapy Combined With Midostaurin for Flt3 Mutated Aml. Results From the Ncri Aml19 “Midotarg” Pilot Trial

Russell, Nigel H.; Wilhelm-Benartzi, Charlotte S.; Othman, Jad; Dillon, Richard; Potter, Nicola; Jovanović, Jelena; Gilkes, Amanda F.; Batten, Leona M; Canham, Joanna; Hinson, Emily L; Kottaridis, Panagiotis D.; Cavenagh, James D.; Arnold, Connie L.; Dennis, Michael; Knapper, Steven

doi:10.1097/01.hs9.0000843396.14484.b9

Cited by 8 publications

(11 citation statements)

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“…Finally, the third published abstract concentrated on MIDOTARG pilot trial results evaluating GO+MIDO+IC safety in 59 newly diagnosed FLT3+ AML and the impact on MRD kinetics. 8 Induction course treatment compliance was comparable to our results (100% vs. 100%). The difference between the MIDOTARG pilot trial and our study was the number of GO doses during induction treatment (2 vs. 3, respectively).…”

supporting

confidence: 87%

“…2,8 Furthermore, CR/CRi was achieved in 88% vs. 91% in our study. 8 In our study, only one patient died due to infection in molecular CR (9%). Our study's major strength is its unique focus on a homogenous patient cohort with FLT3mutated/CD33+ AML treated by GO+MIDO+IC at two academic hematology centers.…”

mentioning

confidence: 41%

“…There have only been limited conference abstracts of ongoing studies published. [6][7][8] Since both drugs were available at once for newly diagnosed AML patients in real life, and the combining of GO plus MIDO with standard IC did not represent a pharmacological contraindication, we decided to employ and retrospectively evaluate the effectiveness and safety of a GO+MIDO+standard IC in patients treated at two Czech hematological centers.…”

Section: Main Bodymentioning

confidence: 99%

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Gemtuzumab ozogamicin plus midostaurin in conjunction with standard intensive therapy for FLT3- mutated acute myeloid leukemia patients – Czech center experience

et al. 2023

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confidence: 87%

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confidence: 41%

Section: Main Bodymentioning

confidence: 99%

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Gemtuzumab ozogamicin plus midostaurin in conjunction with standard intensive therapy for FLT3- mutated acute myeloid leukemia patients – Czech center experience

et al. 2023

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“…In this context, we and others have shown that midostaurin can be safely combined with DA 1 GO, 19,20 and studies with FLAG-Ida 1 GO are planned. The survival benefit of FLAG-Ida 1 GO in NPM1 mut AML was supported by MRD analysis, where patients treated with FLAG-Ida 1 GO had faster, deeper clearance of NPM1 transcripts than those receiving DA 1 GO.…”

mentioning

confidence: 90%

Fludarabine, Cytarabine, Granulocyte Colony-Stimulating Factor, and Idarubicin With Gemtuzumab Ozogamicin Improves Event-Free Survival in Younger Patients With Newly Diagnosed AML and Overall Survival in Patients With NPM1 and FLT3 Mutations

Russell,

Wilhelm-Benartzi,

Othman

et al. 2024

JCO

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PURPOSE To determine the optimal induction chemotherapy regimen for younger adults with newly diagnosed AML without known adverse risk cytogenetics. PATIENTS AND METHODS One thousand thirty-three patients were randomly assigned to intensified (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin [FLAG-Ida]) or standard (daunorubicin and Ara-C [DA]) induction chemotherapy, with one or two doses of gemtuzumab ozogamicin (GO). The primary end point was overall survival (OS). RESULTS There was no difference in remission rate after two courses between FLAG-Ida + GO and DA + GO (complete remission [CR] + CR with incomplete hematologic recovery 93% v 91%) or in day 60 mortality (4.3% v 4.6%). There was no difference in OS (66% v 63%; P = .41); however, the risk of relapse was lower with FLAG-Ida + GO (24% v 41%; P < .001) and 3-year event-free survival was higher (57% v 45%; P < .001). In patients with an NPM1 mutation (30%), 3-year OS was significantly higher with FLAG-Ida + GO (82% v 64%; P = .005). NPM1 measurable residual disease (MRD) clearance was also greater, with 88% versus 77% becoming MRD-negative in peripheral blood after cycle 2 ( P = .02). Three-year OS was also higher in patients with a FLT3 mutation (64% v 54%; P = .047). Fewer transplants were performed in patients receiving FLAG-Ida + GO (238 v 278; P = .02). There was no difference in outcome according to the number of GO doses, although NPM1 MRD clearance was higher with two doses in the DA arm. Patients with core binding factor AML treated with DA and one dose of GO had a 3-year OS of 96% with no survival benefit from FLAG-Ida + GO. CONCLUSION Overall, FLAG-Ida + GO significantly reduced relapse without improving OS. However, exploratory analyses show that patients with NPM1 and FLT3 mutations had substantial improvements in OS. By contrast, in patients with core binding factor AML, outcomes were excellent with DA + GO with no FLAG-Ida benefit.

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“…More recently, results from the UK NCRI AML19 in NPM1 mutated patients treated with 2 courses of FLAG-Ida-GO who were NPM1 MRD negative in the peripheral blood [28] had a similar OS and RFS independently of the number of consolidations (zero, one, or two) in a non-randomised comparison [29].…”

Section: Chemotherapymentioning

confidence: 99%

Optimal Post-Remission Consolidation Therapy in Patients with AML

Jimenez-Chillon,

Dillon,

Russell

2023

Acta Haematol

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Background: Despite recent advances, 40–85% of patients with acute myeloid leukaemia (AML) achieve complete remission after intensive chemotherapy. However, without optimal treatment after remission, the risk of relapse remains high. Summary: A variable number of consolidation cycles consisting of intermediate doses of cytarabine are the most commonly used regimens in low-intermediate-risk AML, while patients at higher risk of relapse should consolidate response by proceeding to HSCT. Different post-consolidation (maintenance therapies) have demonstrated their benefit in prolonging relapse-free survival, and others are still under investigation. Careful consideration should be given to which patients benefit most from each of these interventions, considering that the risk of relapse is dynamic. Key Messages: Patients consolidated with chemotherapy should receive either 2 courses of HDAC or no more than 3–4 cycles of IDAC with dose reduction in patients over 60 years. Patients with mutated FLT3 AML benefit from post-consolidation maintenance with FLT3 inhibitors, and selected patients not fit for adequate consolidation may benefit from CC-468 maintenance. Patients at higher risk of relapse should proceed to allogeneic SCT as soon as possible, opting for a more intensive conditioning in patients younger than 55 years. However, autologous HSCT may still have role in favourable-risk MRD-negative AML. Multiple treatment options targeting MRD are emerging, either as definitive treatment or as a bridge to allogeneic transplantation, and are likely to become increasingly relevant.

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S126: Gemtuzumab-Based Induction Chemotherapy Combined With Midostaurin for Flt3 Mutated Aml. Results From the Ncri Aml19 “Midotarg” Pilot Trial

Abstract: Book distributed under the Attribution-NonCommercial-NoDerivs (CC BY-NC-ND) which allows third parties to download the articles and share them with others as long as they credit the author and the Abstract Book, but they cannot change the content in any way or use them commercially.

Cited by 8 publications

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Gemtuzumab ozogamicin plus midostaurin in conjunction with standard intensive therapy for <i>FLT3</i>- mutated acute myeloid leukemia patients – Czech center experience

Gemtuzumab ozogamicin plus midostaurin in conjunction with standard intensive therapy for <i>FLT3</i>- mutated acute myeloid leukemia patients – Czech center experience

Fludarabine, Cytarabine, Granulocyte Colony-Stimulating Factor, and Idarubicin With Gemtuzumab Ozogamicin Improves Event-Free Survival in Younger Patients With Newly Diagnosed AML and Overall Survival in Patients With NPM1 and FLT3 Mutations

Optimal Post-Remission Consolidation Therapy in Patients with AML

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