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1474 Impact of Recent Advancements in Relapsed/Refractory Acute Myeloid Leukemia on Overall Survival in Clinical Practice

Program: Oral and Poster Abstracts
Session: 613. Acute Myeloid Leukemias: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Research, Acute Myeloid Malignancies, AML, Clinical Practice (Health Services and Quality), Clinical Research, Diseases, real-world evidence, Therapies, Myeloid Malignancies
Saturday, December 9, 2023, 5:30 PM-7:30 PM

Thuy Ho, M.D.1*, Juhi Gor, M.D.1*, Graeme Murray, M.D., Ph.D.1*, Ian Bouligny, MD2 and Keri Maher, DO1

1Massey Cancer Center, Virginia Commonwealth University, Richmond, VA
2Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX

Introduction: The treatment landscape for relapsed or refractory acute myeloid leukemia (RR AML) is quickly evolving, guided by routine genetic profiling at diagnosis and relapse. In recent years, there has been a surge in FDA approvals for novel therapies, including venetoclax in combination with a hypomethylating agent (VEN + HMA), gilteritinib, ivosidenib, and enasidenib. Additionally, newer multi-agent combination chemotherapy regimens, such as fludarabine, cytarabine, idarubicin, and venetoclax (FLAG-Ida + VEN), have been increasingly used for RR disease. The year-by-year impact of the availability of these therapies on overall survival remains unclear.

Methods: A cohort of 257 subsequent patients aged > 18 years with R/R AML treated at VCU Massey Comprehensive Cancer Center was retrospectively studied from 2015 to 2019. Only 2015-2019 were studied to avoid confounding from effects of the COVID-19 pandemic. Data was obtained from the medical record including cytogenetic and molecular profile, treatment regimens, allogeneic stem cell transplantation status (HCT), and survival. Disease was categorized by ELN 2022 genetic risk stratification. Median overall survival (mOS) was compared across individual calendar years using the Kaplan-Meier method. Categorical variables were analyzed using Fisher’s exact test.

Results: The median age of all patients with R/R AML was 61.4 years (range, 19.9-84.8) and median ECOG performance status was 1 (range, 0-4). The median Charlson Comorbidity Index was 4 (range, 0-14). Of the 248 patients for whom data on ELN 2022 genetic risk was available, 30 (12.1%) patients had ELN favorable risk disease, 65 (26.2%) had intermediate risk, and 151 (60.9%) had adverse risk disease. The median OS in 2015 was 5.8 months for all patients compared to 6.9 months in 2019 (p=0.38). When stratified by ELN risk category, patients with R/R favorable risk disease in 2019 had improved mOS compared to those in 2015 (mOS not reached vs. 7.1 months, respectively, HR 0.30 [95% CI 0.08-1.13], p=0.0400) (Fig. 1). There was no significant difference in mOS for the intermediate or adverse risk R/R AML cohorts over time. The proportions of patients with relapsed disease in 2019 who received alloSCT (39.2%) were numerically higher than in 2015 (26.3%), but were not statistically significant (p=0.259). Next, we studied relapsed/refractory therapeutic regimen usage over time. Coinciding with the approval of venetoclax, there was a marked increase in the percentage of patients who received a VEN + HMA beginning in 20182019, which corresponded to a decline in HMA monotherapy, as well as increased use of targeted therapeutics (Fig. 2).

Conclusions: Prognosis for relapsed/refractory AML remains poor despite advances in novel therapeutics. While modest improvements in survival have been achieved, this is largely for ELN 2022 favorable-risk disease. Our work highlights the need for novel therapeutics aimed at those with relapsed or refractory disease. Our findings demonstrate reduced use of conventional chemotherapy in RR AML, with increased reliance on small molecule inhibitors and targeted therapies.

Disclosures: Maher: Sobi (Doptelet): Speakers Bureau; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees.

*signifies non-member of ASH