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. 2024 Jul 24;5(4):728-737.
doi: 10.1002/jha2.981. eCollection 2024 Aug.

Real-world outcomes of intensive induction approaches in core binding factor acute myeloid leukemia

Alexandra E Rojek  1 , Benjamin J McCormick  2 , Joanna Cwykiel  3 , Oluwatobi Odetola  3 , Yasmin Abaza  3 , Nhi Nai  4 , Charles E Foucar  5 , Rohan K Achar  6 , Rory M Shallis  6 , Danielle Bradshaw  7 , Meaghan Standridge  8 , Vamsi Kota  7 , Guru Subramanian Guru Murthy  9 , Talha Badar  2 , Anand A Patel  1
Affiliations

Real-world outcomes of intensive induction approaches in core binding factor acute myeloid leukemia

Alexandra E Rojek et al. EJHaem. .

Abstract

Core-binding factor acute myeloid leukemia (CBF-AML) is characterized by the presence of inv(16)/t(16;16) or t(8;21) and is classified as a favorable risk by the 2022 European LeukemiaNet (ELN) guidelines. The CD33-targeting antibody-drug conjugate, gemtuzumab ozogamicin (GO), is commonly added to intensive chemotherapy (IC) in CBF-AML. We sought to compare outcomes in patients treated with IC with or without GO in CBF-AML. We included 200 patients with CBF-AML treated with IC across seven academic centers. Induction treatment regimens were categorized as IC alone, IC with GO, or IC with KIT inhibitor (dasatinib or midostaurin). Median follow-up for the whole cohort was 2.5 years. Three-year overall survival (OS) was 70% and 3-year event-free survival (EFS) was 51%. Patients treated with IC with GO experienced a 3-year EFS of 50% compared to those treated with IC alone who experienced a 3-year EFS of 47%, with no statistically significant difference (p = 0.62). Similarly, those treated with IC with GO did not experience an improved OS compared to those treated with IC alone (p = 0.67). Patients treated with IC with KIT inhibitor experienced a significantly improved 3-year EFS of 85% compared to those with IC with or without GO (p = 0.04). We find in our study that there is no survival benefit in patients treated with IC with the addition of GO; improved EFS was seen in patients with CBF-AML treated with IC plus KIT inhibitors, consistent with outcomes noted in prospective studies utilizing this approach.

Keywords: acute myeloid leukemia; core binding factor; intensive chemotherapy.

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Conflict of interest statement

Alexandra E. Rojek, Benjamin J. McCormick, Joanna Cwykiel, Oluwatobi Odetola, Nhi Nai, Rohan K. Achar, Danielle Bradshaw, Meaghan Standridge, and Guru Subramanian Guru Murthy declare no conflict of interest.Yasmin Abaza received research funding from Biomea, Curis, Biosight, and ALX Oncology Novartis; honoraria from Servier, Pfizer, BMS, Kite, Astellas, and Rigel. Charles E. Foucar received honoraria from the Binaytara Foundation. Rory M. Shallis received honoraria from Bristol Myers Squibb, Kura Oncology, Gilead Sciences, Rigel, and Servier. Vamsi Kota: Kite: honoraria; Novartis: honoraria; Incyte: research funding; Pfizer: honoraria. Talha Badar served on an advisory board for Takeda, Morphosys, and Pfizer. Anand A. Patel received honoraria from AbbVie and Bristol Myers Squibb; research funding from Krono Bio and Pfizer from AbbVie and Bristol Myers Squibb; research funding from Krono Bio and Pfizer.

Figures

FIGURE 1
FIGURE 1
Sankey plot of treatment patterns from induction chemotherapy through consolidation therapy, and relapse outcomes. *IC, intensive chemotherapy; KITi, KIT inhibitor (dasatinib or midostaurin); GO, gemtuzumab ozogamicin; R/R, relapsed/refractory disease; CR1, first complete remission; CR2, second complete remission; alloSCT, allogeneic stem cell transplantation.
FIGURE 2
FIGURE 2
Event‐free survival outcomes of CBF‐AML patients. (A) By induction chemotherapy regimen—intensive chemotherapy (IC) with gemtuzumab ozogamicin (GO), IC with KIT inhibition, or IC without a targeted inhibitor; (B) by CBF cytogenetic abnormality. *CBF‐AML, core‐binding factor acute myeloid leukemia; IC, intensive chemotherapy.
FIGURE 3
FIGURE 3
Overall survival outcomes of CBF‐AML patients. (A) By induction chemotherapy regimen—intensive chemotherapy (IC) with gemtuzumab ozogamicin (GO), IC with KIT inhibition, or IC without a targeted inhibitor; (B) by CBF cytogenetic abnormality. *CBF‐AML, core‐binding factor acute myeloid leukemia; IC, intensive chemotherapy.
FIGURE 4
FIGURE 4
Survival outcomes by post‐induction FISH‐ and PCR‐based residual disease status in evaluable patients. (A) Event‐free survival, (B) Overall survival. *FISH, fluorescence in situ hybridization; PCR, polymerase chain reaction.
FIGURE 5
FIGURE 5
Somatic mutations in patients with CBF‐AML. Somatic mutations are shown in blue and non‐mutated genes are in gray. *CBF‐AML, core‐binding factor acute myeloid leukemia.
See this image and copyright information in PMC

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