LLM Abstracts Supplement

LLM Abstracts Supplement P-001 | A Case of Acute Undifferentiated Leukemia: Diagnostic and Therapeutic Challenges Khan Hina, Jafry Rabab, Rios Adan Department of Hematology/Oncology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA; 2 Aga Khan Medical University, Karachi, Pakistan Introduction/Background/Significance: Acute undifferentiated leukemia (AUL) is a rare, aggressive leukemia lacking expression of lineage-specific markers. Diagnostic and therapeutic challenges include differentiating AUL from acute leukemias of ambiguous lineage (ALALs). The diagnosis of AUL is made once comprehensive immunophenotyping, cytogenetics, and molecular genomics exclude any lineage-specific leukemia. Materials and Methods/Case Presentation/Objective: A 56-year-old woman presented with easy bruising, petechial rash, and fevers for 2 weeks. Laboratory tests revealed a hemoglobin of 8.5 g/dL, WBC 8.1 K WBC/μL, and platelets of 5,000 platelets/μL. Serum LDH was mildly elevated at 288 U/L. Peripheral blood smear showed increased blasts. Bone marrow aspirate and biopsy showed 75% blasts that expressed no specific lineage markers. Cytogenetics were normal, and molecular findings revealed the presence of an IDH1 mutation. A diagnosis of AUL was confirmed. The patient was treated with FLAGIDA (fludarabine 30 mg/m x 5 days, cytarabine 1.5 g/m x 5 days, idarubicin 8 mg/m x 3 days, and G-CSF with tbo-filgastrim 480 μg from day 1 x 7 days). Her induction course was complicated by neutropenic fever and sepsis requiring intravenous antibiotics. A bone marrow from day 23 of treatment revealed a complete response with incomplete hematologic recovery. The patient was referred for allogenic hematopoietic stem cell transplantation (HSCT). Results/Description/Main Outcome Measure: ALALs are extremely rare hematologic malignancies, accounting for 1 year duration. P-002 | A First-in-Human Study of CD123 Natural Killer Cell Engager (NKCE) SAR443579 in Relapsed or Refractory Acute Myeloid Leukemia (R/R AML), B-cell Acute Lymphoblastic Leukemia (B-ALL) or High Risk-Myelodysplasia (HR-MDS) Stein Anthony, Lavrencic Mojca, Garciaz Sylvain, Huls Gerwin, Maiti Abhishek, Boissel Nicolas, Botton Stephane, Fleming Shaun, Zwaan Michel, de Leeuw David C., Desai Pinkal, Arellano Martha, Avigan David, Langemeijer Saskia, Jensen Kyle, Wagenaar Timothy, Mi Gu, Abbadessa Giovanni, Bajel Ashish City of Hope National Medical Center, Duarte, CA, USA; Erasmus University Medical Center, Rotterdam, Netherlands; Institut PaoliCalmettes, Aix-Marseille University, Marseille, France; University Medical Center Groningen, Groningen, Netherlands; MD Anderson Cancer Center, Houston, TX, USA; Hôpital Saint-Louis, Paris, France; Institut Gustave Roussy, Paris, France; Alfred Health, Melbourne, Australia; Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands; Amsterdam University Medical Center, Amsterdam, Netherlands; Weill Cornell Medicine, NY, USA; Emory University, Atlanta, GA, USA; Beth Israel Deaconess Medical Center, MA, USA; Radboud University Medical Center, Nijmegen, Netherlands; Sanofi, Cambridge, MA, USA; Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, Australia Introduction/Background/Significance: SAR443579, a trifunctional antiCD123 NKp6/CD16 NKCE, enables a cytolytic synapse between NK cells and CD123+ tumor cells resulting in NK cell activation and tumor cell killing. Here we report preliminary safety, efficacy, and PK/PD data of SAR443579 from a phase 1/2 trial in patients with R/R AML, B-ALL or HR-MDS (NCT05086315). Accepted: 19 September 2023 DOI: 10.1002/ajh.27112 Am J Hematol. 2023;98:S3–S57. wileyonlinelibrary.com/journal/ajh © 2023 Wiley Periodicals LLC. S3 Materials and Methods/Case Presentation/Objective: Patients received SAR443579 intravenously twice weekly or once weekly (QW), dependent on dose level (DL) in first 2 weeks of cycle 1, and QW for rest of the induction cycles. Patients receive approximately three 28-day induction cycles and, upon achieving a complete remission (CR) or incomplete hematologic recovery (CRi) per International Working Group criteria, may transition to a 56-day maintenance period with dosing approximately every 29 days if not a candidate for stem cell transplantation. Peripheral blood (to determine plasma concentrations and immunogenicity) and bone marrow samples were collected for PK/PD analysis during each induction cycle. Cytokines analysis, including IL-6, INFα and IFNγ, as potential safety and PD markers, was performed. Primary objectives were safety/tolerability and antileukemic activity (composite complete remission [CRc]=CR+CRi). Results/Description/Main Outcome Measures: As of April 26, 2023, 23 patients (median age: 70 years) with R/R AML across 6 DLs (3 patients in DL1 and 4 each in DL2-DL6) were included in the safety population. Nine patients (39.1%) reported prior hematopoietic stem cell transplantation and 18 (78.3%) had prior exposure to venetoclax. Patients received escalating doses between 10-3000μg/kg/dose in cycle 1 and 100-3000μg/kg QW for other induction cycles. Dose limiting toxicities (DLTs) were not observed in 21 DLT-evaluable patients, including the highest dose of 3000μg/kg QW. CR/CRi was achieved in 3 of 16 (18.8%) patients treated at a maximal target dose of ≥1000 μg/kg/infusion. Treatment emergent adverse events (TEAEs) were reported in 22 (95.7%) patients, with grade ≥3 TEAEs in 18 (78.3%) and treatment related adverse events (TRAEs) in 16 patients (69.6%), respectively. The most common TRAE was infusion-related reactions (n=13 [56.5%]). Decreased appetite, headache, diarrhea, and nausea were reported in 2 (8.7%) patients, respectively. There was 1 case of cytokine release syndrome (grade 1) and no case of immune effector cell-associated neurotoxicity syndrome. CRc rate was 13.0% (3/23 patients evaluable for response). The median duration of CR/CRi is not estimable. From Dec 14, 2021 to Oct 17, 2022, 19 patients were treated across 5 DLs (3 in DL1 and 4 each in DL2 to DL5). In these patients, early immunogenicity was 26% with no apparent impact on safety/efficacy to date. Post first administration of SAR443579, circulating maximum concentration increased with dose increase with a supra-dose proportionality between DL1 and DL5. PK linearity was achieved at 3000μg/kg QW (DL5) at the end of cycle 1. CRS levels of IL-6 ( >500/1000pg/mL) were measured in a single DL1 patient. Conclusions: SAR443579 was well tolerated up to doses of 3000μg/ kg QW with observed clinical benefit in patients with R/R AML. The trial continues to accrue patients. P-003 | A Fulminant Leukemic Presentation of Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) Responsive to Tagraxufusp-erzs Lewis Toni-Ann, Amin Adina, Ghalehsari Nima, Grutman Gennadiy, Astrow Alan B.. New YorkPresbyterian Brooklyn Methodist Hospital Introduction/Background/Significance: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare disease accounting for less than 1% of all hematologic malignancies. The mainstay of treatment is allogenic stem cell transplantation (allo-SCT) in consolidation of previous response. We report a case of rapidly progressive BPDCN with marrow failure and peripheral blood involvement responsive to Tagraxofusp-erzs, a CD123-targeted monoclonal antibody conjugated to diphtheria toxin approved by the Food and Drug Administration (FDA) in 2019. Materials and Methods/Case Presentation/Objective: A 71-year-old female with chronic well-controlled hypertension presented to an outside hospital for chest pain radiating to the back. Differential diagnosis included aortic dissection; however, emergency imaging revealed a uterine mass with regional adenopathy, and laboratory testing revealed 45,000 platelets, 18,300 WBC, without anemia or neutropenia. She was discharged without definitive diagnosis or treatment, and percutaneous inguinal lymph node biopsy at this facility was reported as a "poorly differentiated neoplasm" not otherwise characterized. The patient then presented to us two weeks later with increasing leftsided back pain and progressive loss of performance status. Repeat laboratory testing revealed an abnormal CBC with 15,900 WB