Abstracts Clinical Lymphoma, Myeloma & Leukemia September 2023 S288 ARF6 disrupts sphingolipid homeostasis in AML cells, suppresses their proliferation but spares the host’s normal physiology. Keywords: AML, acute myeloid leukemia, metabolic homeostasis, drug target AML-303 Tagraxofusp, an Anti‑CD123 Therapy, in Patients With Blastic Plasmacytoid Dendritic Cell Neoplasm and Prior or Concomitant Hematologic Malignancies: Subgroup Analysis of a Pivotal Trial Naveen Pemmaraju MD1, Marina Konopleva MD, PhD1, Kendra Sweet MD2, Anthony Stein MD3, Sumithira Vasu MD4, David Rizzieri MD5, Eunice S. Wang MD6, Hagop Kantarjian MD1, Christopher Brooks PhD7, Tariq Mughal MD7,8, Andrew A. Lane MD, PhD9 1The University of Texas MD Anderson Cancer Center, Houston, USA. 2H. Lee Moffitt Cancer Center, Tampa, USA. 3City of Hope National Medical Center, Duarte, USA. 4The Ohio State University, Columbus, USA. 5Duke University Medical Center, Durham, USA. 6Roswell Park Comprehensive Cancer Center, Buffalo, USA. 7Stemline Therapeutics Inc, New York City, USA. 8Division of Hematology-Oncology, Tufts University School of Medicine, Boston, USA. 9Dana-Farber Cancer Institute, Boston, USA Context: Blastic plasmacytoid dendritic cell neoplasm (BPDCN), an aggressive myeloid malignancy, derives from plasmacytoid dendritic cells that overexpress CD123. BPDCN may occur as a secondary malignancy, with ~10–20% of patients having prior or concomitant hematologic malignancies (PCHM). Tagraxofusp (TAG), a CD123-targeted therapy, is the only approved treatment for BPDCN. The pivotal trial demonstrated high (overall response rate [ORR] 75%) and durable responses in first-line patients. Objective: Determine complete response (CR + clinical CR [CRc]: CR with residual skin abnormality not indicative of active disease), ORR, overall survival (OS), and safety in patients with and without PCHM. Design: Subgroup analysis of a 4-stage, single-arm phase 1/2 trial (NCT02113982). Setting: US, multicenter. Patients: 65 patients with BPDCN (8 [12%] with PCHM and 57 without), according to WHO classification or confirmed by hematopathology, in firstline setting. Interventions: TAG 12 mcg/kg intravenously days 1–5 of a 21-day cycle. Main Outcome Measures: Response criteria for BPDCN; CTCAE criteria. Results: Baseline characteristics were similar between patients with or without PCHM (median ages 69 and 68 years). Length of time since PCHM diagnosis prior to BPDCN diagnosis ranged from 4–14 years. Similar rates of CR/ CRc (50% vs 58%) and ORR (88% vs 74%) were seen across patients with and without PCHM, respectively. One PCHM patient bridged to transplant. Median OS was longer in patients without PCHM vs with PCHM (18.9 vs 6.3 months, P=0.0021). Most frequent treatment-related adverse events (TRAEs) in patients with PCHM were increased AST (38%), increased ALT, weight gain, hypoalbuminemia (25% each). No patients with PCHM experienced capillary leak syndrome (CLS). In patients without PCHM, most common TRAEs were increased ALT (56%), increased AST (53%), hypoalbuminemia (40%), thrombocytopenia (35%), pyrexia (32%), weight gain (28%), nausea (25%), CLS (21%). Conclusions: In this small subgroup, there is evidence that TAG has efficacy in first-line treatment of BPDCN with PCHM. High response rates were observed and consistent in patients with and without PCHM. The safety profile was manageable and predictable; PCHM did not appear to predispose patients to different TRAEs. Findings reinforce the importance of a correct BPDCN diagnosis to enable diseasedirected treatment. Keywords: myeloid malignancies, targeted therapy, tagraxofusp, CD123, BDPCN AML-308 Real‑World (RW) Outcomes With Venetoclax (VEN) in Patients With Acute Myeloid Leukemia (AML) From COTA, a US RW Evidence Database Eytan Stein MD1, Sejla Hodzic MD2, Henry Owusu PhD3, Dhrubajyoti Pathak MBBS, DCH, MBA, MScPM3, Summera Zhou MSc4 1Memorial Sloan Kettering Cancer Center, New York, USA. 2Novartis Pharmaceuticals Corporation, East Hanover, USA. 3Novartis Pharma AG, Basel, Switzerland. 4Genesis Research, Hoboken, USA Background: VEN + hypomethylating agents (HMAs)/low-dose cytarabine was approved for use in patients with AML aged ≥75 years or ineligible for intensive chemotherapy (CT) in 11/2018. To understand the use, safety, and efficacy of VEN in clinical practice, the COTA AML RW evidence database was analyzed. Methods: This retrospective, descriptive analysis used deidentified electronic health record data from the US COTA AML database from 01/2018 to 09/2022. Adults with AML initiating first-line (1L) treatment on/ after 01/01/2018 who received ≥1 VEN treatment were included. Patients with no diagnosis date or concurrent primary malignancies were excluded. Follow-up was until the last recorded visit or death. Results: Of 3836 patients with AML in COTA, 1163 initiated 1L treatment in/after 2018; of these, 636 received ≥1 VEN treatment at any point and were included. Most VEN-treated patients were seen by community healthcare providers (64%). TP53 (28%), RUNX1 (25%), TET2 (24%), ASLX1 (22%), and DNMT3A (22%) mutations were most common among those frequently tested up to 90 days post-AML diagnosis. Of patients who received VEN, 47% received 1L VEN, and 42% received VEN + HMAs in any line. Of patients with treatment prior to VEN (pretreated), 74% were previously treated with CT. 1L vs pretreated patients were treated in community centers more often (73% vs 56%), had more comorbidities (56% vs 40%), and had more baseline TP53 mutations (19% vs 10%). Of 284 VEN-treated patients with available response data, 63% had complete responses per clinicianstated responses. Median overall survival (mOS) in VEN-treated patients was 14.4 months from 1L treatment initiation. mOS from diagnosis was 14 and 18 months in newly diagnosed and pretreated patients, respectively. Dose reductions (among patients with dosing information) and discontinuations occurred in 29% and 53% of VEN-treated patients, respectively. Median time to discontinuation was 49.5 days; median duration of VEN treatment was 78 days.
RkJQdWJsaXNoZXIy MTk3NTQxMg==