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2889 Intensive Induction Chemotherapy with or without Gemtuzumab Ozogamicin Among Patients with Core-Binding Factor Acute Myeloid Leukemia

Program: Oral and Poster Abstracts
Session: 615. Acute Myeloid Leukemias: Commercially Available Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster II
Hematology Disease Topics & Pathways:
Research, Acute Myeloid Malignancies, AML, Biological therapies, Antibody Therapy, Non-Biological therapies, Clinical Research, health outcomes research, Chemotherapy, Combination therapy, Diseases, real-world evidence, Therapies, Myeloid Malignancies
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Alexandra E. Rojek, MD1, Benjamin J. McCormick, MD2*, Joanna Cwykiel, MD3*, Oluwatobi Odetola, MD3, Yasmin Abaza, MD3, Rohan Achar, MD, MS4*, Rory M. Shallis, MD4, Danielle Bradshaw, MD5*, Meaghan Standridge, MD6*, Vamsi K. Kota, MD7, Talha Badar, MD2 and Anand Ashwin Patel, MD1

1Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL
2Division of Hematology-Oncology, Blood and Marrow Transplantation Program, Mayo Clinic, Jacksonville, FL
3Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL
4Section of Hematology, Department of Internal Medicine, Yale School of Medicine, Yale University, New Haven, CT
5Georgia Cancer Center, Augusta University Medical Center, Augusta, GA
6Department of Medicine, Augusta University, Augusta, GA
7Georgia Cancer Center, Augusta University, Augusta, GA

Background: 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 favorable risk by the 2022 European LeukemiaNet (ELN) guidelines. High remission rates are observed in the setting of cytarabine- or anthracycline-based induction regimens. The CD33-targeted antibody-drug conjugate gemtuzumab ozogamicin (GO) is FDA-approved for use in newly-diagnosed CD33+ AML; a meta-analysis of 5 prospective randomized studies investigating intensive chemotherapy (IC) +/- GO demonstrated an improved overall survival (OS) with the addition of GO to IC for favorable-risk AML (Hills et al, Lancet Oncol 2014). The trials included in the meta-analysis did not restrict inclusion criteria to CBF-AML alone and there remains variation amongst IC regimens utilized in CBF-AML treatment. In addition, IC combined with the KIT inhibitor dasatinib has shown remission rates and promising overall survival in prospective studies (Paschka et al, Leukemia 2018; Marcucci et al, Blood Adv 2020). We set out to investigate the outcomes of patients (pts) with CBF-AML treated with IC +/- targeted agents (GO or KIT inhibitor) across 5 institutions that are part of the Consortium on Myeloid Malignancies and Neoplastic Diseases (COMMAND).

Methods: Retrospective chart review was done to identify pts who were treated with IC with AML harboring inv(16)/t(16;16) or t(8;21) identified on cytogenetics, from January 2010 through April 2023, and were treated across 5 geographically-diverse academic institutions. Pt clinical characteristics, cytogenetics, molecular mutations, treatment, relapse, and OS data were collected. Relapse-free survival (RFS) and OS were both analyzed using Kaplan-Meier analysis.

Results: One-hundred forty-nine consecutive pts with CBF-AML were identified, 76 (51%) with inv(16) and 73 (49%) with t(8;21). Median age of pts was 47 years (yrs) (range 18-80yrs), with 64% male pts, and 106 (71%) pts had an ECOG performance status of 0-1. One-hundred seven (72%) pts identified as non-Hispanic White, 22 (15%) identified as non-Hispanic Black, and 12 (8%) identified as Hispanic. Molecular testing via next-generation sequencing was available for 124 pts (83%); 49 (33%) pts had adverse-risk ELN cytogenetics or mutations when excluding CBF status, and 27 (18%) pts harbored KIT mutations. Other baseline pt characteristics are listed in Table 1A.

All pts underwent induction with IC; 44 (30%) pts received IC + GO, 21 (14%) received IC + KIT inhibitor (14 received dasatinib, 7 received midostaurin), and the remaining 84 (56%) received IC without a targeted agent. One-hundred fourteen (77%) pts achieved a complete response (CR) to induction therapy, and 1 pt experienced induction-related mortality. Fluorescence in-situ hybridization (FISH) data was available in 82 pts at end of induction with 83% achieving FISH negativity. Measurable residual disease (MRD) testing was done by polymerase chain reaction (PCR) in 62 pts with 76% achieving MRD-negativity.

One-hundred forty pts underwent consolidation with a median of 3 cycles of chemotherapy; 21 (15%) pts received GO with consolidation and 17 (12%) received a KIT inhibitor with consolidation. Forty-four (30%) pts underwent allogeneic stem cell transplantation (alloSCT), with 17 in first CR, and 27 after second-line or beyond therapy.

With a median follow-up of 22.5 months, the observed 3-yr RFS was 51% (95% CI: 43-61%) and the 3-yr OS was 69% (95% CI: 61-78%). Pts treated with IC + KIT inhibitor had significantly improved 3-yr RFS of 85% (95% CI: 70-100%) compared to other pts, including those who received IC + GO who had a 3-yr RFS of 51% (95% CI: 37-70%) and those who received IC without targeted therapy who had a 3-yr RFS of 45% (95% CI: 35-58%) (p = 0.02) (Figure 1). Full survival statistics are shown in Table 1B and Figure 1.

Conclusions: In this multi-center retrospective study of pts with CBF-AML undergoing induction with IC regimens with diverse national treatment practices, we find that the addition of GO to IC is not associated with improved outcomes. Pts treated with IC + KIT inhibitor had significantly improved RFS; of note, pts receiving a KIT inhibitor oftentimes continued on maintenance even after consolidation. These data suggest that there may be a role for targeted therapies other than GO to be explored in randomized prospective studies of intensive induction chemotherapy for CBF-AML.

Disclosures: Abaza: Astellas: Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding; Biomea: Research Funding; Biosight: Research Funding; Curis: Research Funding; Rigel: Honoraria, Membership on an entity's Board of Directors or advisory committees; ALX Oncology: Research Funding. Shallis: Rigel: Consultancy; Curio Science: Consultancy; Gilead Sciences: Consultancy; Servier: Consultancy; Bristol Myers Squibb: Consultancy. Kota: Pfizer: Honoraria; Incyte: Research Funding; Novartis: Honoraria; Kite: Honoraria. Patel: Kronos Bio: Research Funding; BMS: Honoraria; AbbVie: Honoraria; Pfizer: Research Funding.

*signifies non-member of ASH