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324 Real-World Analysis of CPX-351 Induction in Acute Myeloid Leukemia-Myelodysplasia Related (AML-MR): An Updated Analysis from the Marrow Consortium

Program: Oral and Poster Abstracts
Type: Oral
Session: 615. Acute Myeloid Leukemias: Clinical and Epidemiological: Treatments and Outcomes in AML in Specific Age Groups, and in Blastic Plasmacytoid Dendritic Cell Neoplasms
Hematology Disease Topics & Pathways:
Research, Acute Myeloid Malignancies, AML, Adult, Clinical Research, Health outcomes research, Diseases, Real-world evidence, Myeloid Malignancies, Study Population, Human
Saturday, December 7, 2024: 5:15 PM

Daniel T Peters, MD1, Deedra Nicolet, MS2*, Yazan F Madanat, MD3, Jesus D Gonzalez-Lugo, MD4, Alexander J. Ambinder, MD, MPH5, Onyee Chan, MD6*, Michael Jamie Hochman, MD7, Najla H. Al Ali, Ms8*, Victoria Klein, MS2*, Krzysztof Mrózek, MD, PhD2, Tara L. Lin, MD4, Alice Mims, MD9, Charles Foucar, MD10 and Joshua F. Zeidner, MD11

1Division of Hematology, University of North Carolina School of Medicine, Chapel Hill, NC
2The Ohio State University Comprehensive Cancer Center, Columbus, OH
3Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX
4Division of Hematologic Malignancies and Cellular Therapeutics, The University of Kansas Cancer Center, Westwood, KS
5Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD
6H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
7Emory University Winship Cancer Institute, Atlanta, GA
8Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
9Division of Hematology, The Ohio State University Comprehensive Cancer Center, Columbus, OH
10University of New Mexico, Ann Arbor, MI
11Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC

Background: Liposomal cytarabine/daunorubicin (CPX-351) is a standard frontline treatment for adult patients (pts) with AML-MR. However, the pivotal trial leading to FDA-approval of CPX-351 enrolled pts aged ≥60 years (y) with: 1) therapy-related AML (t-AML), 2) AML with antecedent myelodysplastic neoplasm (MDS) or chronic myelomonocytic leukemia (CMML), and 3) AML-MR defined by cytogenetics (AML-MRC) based on 2016 WHO criteria. Updated WHO and International Consensus Classification (ICC) guidelines now incorporate MDS-related mutations into the criteria for AML-MR. Thus, there is limited data on the role of CPX-351 in younger pts (<60 y) and/or those with MDS-related gene mutations.

Methods: We retrospectively analyzed clinical and molecular characteristics of pts with AML-MR (based on 2022 WHO/ICC criteria) treated with frontline CPX-351 as part of the Myeloid Malignancy Association on Rapid Research Outcomes Working Group (MARROW) Consortium. Pts were divided into two age groups: <60y and ≥60y. Further analyses were conducted using four subgroups: 1) AML-MR by cytogenetics (AML-MRc), 2) AML-MR by molecular mutations (AML-MRm), 3) AML with antecedent myelodysplastic syndrome or chronic myelomonocytic leukemia (MDS/CMML), and 4) treatment-related AML (t-AML). Pts with internal tandem duplications of FLT3 were excluded. Rates of composite complete remission (CRc: CR + CRi + CRh), complete remission (CR), disease-free survival (DFS), and overall survival (OS) were compared between the groups.

Results: Overall, 267 pts were treated with CPX-351. The median age was 63y (range, 21-78); median age was 55y and 67y in the younger (n=96) and older cohort (n=171), respectively. The older cohort was predominantly male (72%) whereas more female pts were in the younger cohort (54%). The majority of younger and older groups were White (75% vs 87%) followed by Black patients in 18% vs 7%, respectively. Clinical characteristics at diagnosis were similar in both age groups, including median hemoglobin (8.1 vs 8.7g/dL), platelets (46 vs 50 x 109/L), WBC count (3.4 vs 4.4 x 109/L), and bone marrow blast percent (32 vs 30.5%). By the 2022 European LeukemiaNet risk classification, most pts (with complete classification data; n=180) were categorized in the adverse-risk group (n=147, 82%) with a higher percentage in the younger cohort (n=39; 89%).

Within the entire cohort, 58% (n=156) had AML-MRc, 40% had AML-MRm (n=107), 39% had antecedent MDS/CMML (n=105), and 18% had t-AML (n=49). Forty-three (17%) pts had TP53 mutation (TP53m). When comparing younger and older age groups, there were differences in proportion of AML-MR subgroups: AML-MRc (66.7 vs 53.8%; p=0.057), AML-MRm (30.2 vs 45.6%; p=0.029), antecedent MDS/CMML (32.3 vs 43.3%; p=0.081), t-AML (26 vs 14%; p=0.018). AML-MRm identified were ASXL1 (28%), RUNX1 (28%), SRSF2 (28%), STAG2 (21%), U2AF1 (20%), BCOR (18%), SF3B1 (14%), EZH2 (11%), ZRSR2 (4%). Mutation percentages were similar between younger and older age groups, though with numerical difference noted in ASXL1 (n=4 vs 25; 14 vs 32%; p=0.08).

Overall, the cCR and CR rates were 58% and 36%, respectively; median OS was 1.3 years. Partitioning by age did not demonstrate a significant difference in cCR (54% vs 60%; p=0.36) or CR (36% vs 38%) between younger and older groups, respectively. By excluding TP53m, response rates were improved in both age groups: cCR (56% vs 65%; p=0.24), CR (35% vs 41%; p=0.46), but there was still no difference between age groups. Further, there was no significant difference in cCR between age groups when analyzed by AML-MR subgroup: AML-MRc (50 vs 61%; p=0.34) , AML-MRm (62 vs 64%; p=0.82), antecedent CMML/MDS (48% vs 52%; p=0.81), or t-AML (72 vs 61%; p=0.54). Median OS among AML-MR subgroups divided by <60y and ≥60y showed the longest OS in younger pts with AML-MRm only: AML-MRc (0.90 vs 1.66y; p=0.39), AML-MRm (3.17 vs 1.63y; p=0.14), antecedent CMML/MDS (0.89 vs 1.13y; p=0.86), and t-AML (1.88 vs 1.27y; p=0.66).

Conclusions: This real-world analysis demonstrates no significant difference in outcomes between younger and older age groups treated with frontline CPX-351 for AML-MR. AML-MRm was more common in older pts in this study, yet younger pts with AML-MRm appeared to have the best overall survival outcomes with CPX-351. Further research is needed to validate these results and explore the subgroups of pts with AML-MR that may derive most benefit from CPX-351.

Disclosures: Madanat: OncLive, MD Education, Sierra Oncology, Stemline, MorphoSys: Consultancy; Taiho Oncology, Rigel Pharmaceuticals, Novartis: Consultancy; Sierra Oncology, Stemline Therapeutics, Blueprint Medicines, Morphosys, Taiho Oncology, SOBI, Rigel Pharmaceuticals, Geron, Cogent Biosciences and Novartis: Other: Advisory Board; Blueprint Medicines, MD Education, and Morphosys: Other: travel; BMS, Kura Oncology, BluePrint Medicines, Geron: Consultancy. Ambinder: Astellas: Honoraria. Chan: Jazz: Research Funding; Novartis: Honoraria; Abbvie: Honoraria, Research Funding; Aptitude Health: Honoraria; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Syndax: Membership on an entity's Board of Directors or advisory committees. Lin: Aptevo; Bio-Path Holdings; Ciclomed; Cleave; Jazz; Jazz Pharmaceuticals; Leukemia & Lymphoma Society; Kura Oncology; Trovagene: Research Funding; Jazz Pharmaceuticals; Servier: Consultancy. Mims: Treadwell Therapeutics: Membership on an entity's Board of Directors or advisory committees; Daiichi Saynko: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Foghorn Therapeutics: Membership on an entity's Board of Directors or advisory committees; Leukemia and Lymphoma Society Beat AML Study: Other: Senior Medical Director. Foucar: Novartis: Research Funding.

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