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4022 Feasibility and Safety of Outpatient Hypomethylating Agent (HMA) + Venetoclax (Ven) Initiation +/- Ramp-up for Patients (pts) with Newly-Diagnosed Acute Myeloid Leukemia (AML)

Program: Oral and Poster Abstracts
Session: 613. Acute Myeloid Leukemias: Clinical and Epidemiological: Poster III
Hematology Disease Topics & Pathways:
Clinical Practice (Health Services and Quality), Non-Biological therapies, Chemotherapy, Therapies, clinical procedures, Technology and Procedures, Human
Monday, December 12, 2022, 6:00 PM-8:00 PM

Rory M. Shallis, MD1, Julian Weiss1*, Eric S. Winer, MD2, Talha Badar, MD3, Alok Swaroop4*, Peter Doukas4*, Emily Geramita, MD, PhD5, Henry Le6*, Sonal Agarwal, PharmD6*, Man Yee Merl6*, Annie Im, MD7, Yasmin Abaza, MD8, Mark R. Litzow, MD9 and Nikolai A. Podoltsev, MD, PhD1

1Yale University School of Medicine, New Haven, CT
2Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
3Division of Hematology and Oncology, Mayo Clinic Florida, Jacksonville, FL
4Northwestern University, Chicago
5Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA
6Department of Pharmacy Services, Smilow Cancer Hospital at Yale New Haven Health, New Haven
7Univ. of Pittsburgh Cancer Institute, Pittsburgh, PA
8Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL
9Division of Hematology, Mayo Clinic, Rochester, MN

Background: The feasibility/safety of outpatient (outpt) HMA + Ven administration and use of Ven ramp-up to target dose during cycle 1 (C1) for patients (pts) with newly-diagnosed AML is limited to small, single-center analyses of heterogeneous populations. Furthermore, appropriate pt selection for varying approaches is not well-described. Understanding these issues is crucial to efficient and cost-effective care delivery, especially considering the unique challenges older pts face.

In this multi-center analysis, we examined the feasibility and safety of frontline HMA + Ven administration in the outpt setting as well as omission of Ven ramp-up during C1.

Methods: We conducted a multi-center, retrospective study through the Consortium on Myeloid Malignancies and Neoplastic Diseases (COMMAND), a collaboration involving 10 academic institutions. A total of 272 pts with AML treated with frontline HMA + Ven were evaluated; pts presenting in spontaneous tumor lysis syndrome (TLS) or with incomplete data were excluded (n=24). We described the baseline characteristics of the overall study population. Continuous variables were summarized as a median with interquartile range (IQR), and categorical variables were reported as a frequency (percentage). Fisher’s exact test was used for nominal data and Wilcoxon rank-sum testing was used for continuous variables

Results: A total of 64 pts (23.5%) initiated HMA + Ven as outpts. Median age was 76 (IQR: 64-81.25) years, and the majority were male (n=35, 54.7%), white (n=54, 84.4%) and had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1 (n=42, 73.7%). Cardiac comorbidities, prior stroke and diabetes were noted in 32.8%, 12.5% and 10.9% of outpts, respectively. Median total white blood cell count (WBC), marrow and peripheral blasts at presentation were 2.18 (IQR: 1.08-6.75), 38% (IQR: 20-53.5%) and 14% (IQR: 2-35.3%), respectively. Pre-treatment WBC, serum creatinine, uric acid and LDH were noted to be 2.45 (IQR: 1.48-3.98), 0.90 (IQR: 0.77-1.32), 5.05 (IQR: 4.18-5.9) and 212 (IQR: 171-314), respectively. All outpts had a pre-treatment WBC <20, uric acid <10 and creatinine <2; 8 pts (12.5%) had an LDH >500. Baseline characteristics are summarized in Table 1.

When compared with pts receiving C1 of HMA + Ven as an inpt (n=208), outpts were found to have a lower presenting WBC (p=0.002), trend towards lower pre-treatment WBC (p=0.08) and a lower LDH (p=0.0002); pre-treatment uric acid was higher among outpts (p=0.027)(Table 1). There were no differences in disease with mutations with an influence on proliferative AML. Most outpts received allopurinol TLS prophylaxis (ppx); inpts more frequently had rasburicase ppx (13.1% vs. 3.4%, p=0.052).

Most outpts received azacitidine (n=36, 56.3%) vs decitabine (5-day schedule)(n=28, 43.7%) with a similar distribution among inpts (p=0.25). Approximately half of outpts (51.6%) received anti-fungal ppx and required Ven dose reduction during C1. TLS was not observed in any outpts, compared with 10% in inpatients (p=0.0053) including 8% by Cairo-Bishop criteria (p=0.025). There was no difference in the median number of days admitted during the entirety of C1 between inpts and outpts (8 vs 5, p=0.16); 11% of outpts were eventually admitted during C1. Although treatment-related mortality (TRM = up to 90 days from start of C1) was higher among inpts, this was not statistically significant (12.8% vs 1.6%, p=0.20)(Table 1).

Among outpts, approximately 1/3 had no Ven ramp-up (n=20, 31.3%). When compared with outpts with Ven ramp-up (n=44, 68.7%), there were no differences observed in age, ECOG PS, comorbidities, molecular characteristics, presenting or pre-C1 WBC, marrow/blood blasts, serum creatinine, uric acid, LDH, TLS ppx patterns or Ven dose-reduction for antifungal ppx (Table 2). More outpts without Ven ramp-up received decitabine (75% vs 35.9%, p=0.006). Median number of days admitted was higher among outpts with Ven ramp-up (5 vs 0, p=0.039) with one TRM attributed to infection in this group (p=0.99)

Conclusions: Our study demonstrates that many pts with newly-diagnosed AML can safely receive C1 of HMA + Ven as an outpt, particularly those with a pre-treatment WBC <20, uric acid <10 and creatinine <2. We observed no TLS among outpts, including those without Ven ramp-up, which may be safely omitted in select pts. Prospective studies are needed to confirm these findings.

Disclosures: Shallis: Bristol Myers Squibb and Gilead Sciences, Inc: Honoraria; Gilead Sciences, Inc.: Honoraria. Winer: Abbvie: Consultancy; Takeda Pharmaceuticals: Consultancy; Novartis, Jazz Pharmaceuticals, Pfizer, Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Curis: Consultancy. Im: Incyte: Research Funding; CTI Biopharma: Consultancy; Abbvie: Consultancy. Abaza: ALX Oncology: Research Funding; Pfizer: 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; Bristol Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees. Litzow: Amgen: Research Funding; Astellas: Research Funding; Novartis: Research Funding; Syndax: Research Funding; Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees; Actinium: Research Funding; Pluristem: Research Funding; Biosight: Consultancy, Other: Data Monitoring Board; Abbvie: Research Funding. Podoltsev: Constellation Pharmaceuticals: Honoraria; AbbVie: Honoraria; Cogent Biosciences: Other: Independent Data Review Committee ; Pfizer: Honoraria; Agios Pharmaceuticals: Honoraria; Blueprint Medicines: Honoraria; Incyte: Honoraria; CTI BioPharma: Honoraria; Bristol-Myers Squibb: Honoraria; Celgene: Honoraria; PharmaEssentia: Honoraria; Novartis: Honoraria.

*signifies non-member of ASH