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2960 A High Percentage of DNAM-1+ and Low Percentage of Tactile+ NK Cells at Diagnosis Correlate with Complete Response and Survival in AML: A Sub-Analysis of the Ven-a-Qui Pethema Trial

Program: Oral and Poster Abstracts
Session: 617. Acute Myeloid Leukemias: Biomarkers, Molecular Markers and Minimal Residual Disease in Diagnosis and Prognosis: Poster II
Hematology Disease Topics & Pathways:
Research, clinical trials, Non-Biological therapies, Clinical Research, Combination therapy, patient-reported outcomes, immune mechanism, Therapies, immunology, Biological Processes, molecular biology, Technology and Procedures
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Juan Miguel Bergua Burgues1*, Raquel Tarazona, MD. PhD2*, Javier Garcia Casado, MD. PhD3*, Juan J Gordillo, PhD4*, Ignacio Casas Aviles, M.D5*, Rebeca Rodriguez Veiga, M.D6*, Isabel Cano7*, Ferran Vall-Llovera Calmet8*, Antonio Garcia9*, Joaquin Gomez Espuch, MD, PhD10*, Mercedes Colorado11*, Jordi Esteve, MD, PhD12,13,14, Victoria Verdugo Cabeza De Vaca, PhD15*, Maria Antonia Sanpol, MD. PhD16*, Fernando Ramos, MD, MPH, PhD17,18*, Marta Valero, M.D19*, Evelyn Acuña-Cruz, MD20*, Blanca Boluda21*, Joaquin Martinez-Lopez, MD, PhD22,23*, Rosa Ayala, MD, PhD24*, Eva Barragán, PhD25,26,27,28*, David Martinez-Cuadron, PhD29* and Pau Montesinos, PhD, MD27,30,31,32,33*

1Hematology and Hemotherapy Service, San Pedro de Alcántara Hospital, Cáceres, Spain
22Immunology Unit, Department of Physiology, Faculty of Veterenay, Universidad de Extremadura, Cáceres, Spain, caceres, Spain
3Facultad de Veterinaria. Universidad de Extremadura, Garcia Casado, Caceres, Spain
42Immunology Unit, Department of Physiology, Faculty of Veterenay, Facultad de Veterinaria. Universidad de Extremadura, caceres, Spain
6Hematology Department, Hospital La Fe. Valencia, Valencia, Spain
7Hospital Universitari I PolitèCnic La Fe; Dep. of Hematology, University, Valencia, ESP
8Hematology Department, Hospital La Mutua. Tarrassa, Terrassa, ESP
9Hospital Universitario Arnau de Vilanova, LLEIDA, ESP
10University Hospital Virgen De La Arrixaca, Murcia, ESP
11Hematology Department, Hospital Universitario Marques de Valdecilla. Santander, Santander,, Spain
12Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Barcelona, Spain
13Hematopoietic Cell Transplantation Unit, Hospital Clínic de Barcelona, ICHMO, Barcelona, Spain
14Hematology Department, Hospital Clínic Barcelona, Barcelona, Spain
15Department of Hematology, Hospital Universitario De Jerez de la Frontera., Jerez de la Fronera, Spain
16Hematology Department, Hospital de Son Llatzer, Palma de Mallorca, Spain
17Hospital Universitario de León, Leon, Spain
18Grupo Español de Síndromes Mielodisplásicos (GESMD), Madrid, Spain
19Hematology Department, Hospital Arnau de Vilanova. Valencia, Valencia, Spain
20Department of Hematology, Hospital Universitari i Politècnic La Fe, Valencia, Spain
21Hospital Universitari I Politècnic La Fe, Valencia, ESP
22Department of Hematology, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Complutense University, CNIO, CIBERONC, Madrid, Spain
23Hospital Universitario 12 de Octubre, Madrid, Spain
24Hematology Department, Hospital 12 de Octubre (i+12), Centro Nacional de Investigaciones Oncológicas (CNIO), Complutense University, Madrid, Spain
25Molecular Biology Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain
26Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain
27CIBER de Oncología, Madrid, Spain
28Hematology Research Group, Instituto de Investigación Sanitaria La Fe, Valencia, Spain
29Hematology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain
30Nucleus Global, Teaneck, NJ
31Programa Español de Tratamientos en Hematologia, PETHEMA, Valencia, Spain
32Hospital Universitari i Politecnic la Fe, Valencia, Spain
33CIBERONC, Instituto Carlos III, Madrid, Spain

Background: Natural killer (NK) immune status in Acute Myeloid Leukemia (AML) could influence therapeutic results and natural history of the disease.

Objectives: In the phase I/II VEN-A-QUI (Clinical trials NCT04687761) clinical trial for unfit newly diagnosed AML patients (venetoclax+Quizartinib+azacytidine or low-dose cytarabine), it was planned a prospective study of NK populations and their influence in the main clinical outcomes. NK cells were analyzed at the diagnosis in a central laboratory.

Material and methods: We analyzed NK cell subpopulations based in the expression of DNAM-1, TIGIT, TACTILE, CD8, PD-1, TIM-3, LAG-3, NKp44, NKp46, NKp30, CD16, CD85j,KIR2D, NKG2C, NKG2A, CD57, CD6, CD244, NKp80, Perforin, Granulolysin and Granzyme B. We compare composite Complete Remission (CRc) results of the Venetoclax/Quizatinib with Aza or Cytarabine vs. not achieving CRc using t Student. MaxStat statistics was used to test the significant limit of those populations with a significant difference (R-statistics version 4.2.2). Survival analysis comparing significant differences between patients in CRc was performed using LogRank test and Kaplan Maier. Cox survival analysis was performed to evaluate if the presence of this populations could be an independent factor against the European Leukemia Net classification of 2017 and p53. Data of molecular characteristics were obtained with an NGS panel of 40 genes.

RESULTS: The trial included 76 ineligible patients for intensive chemotherapy (37 and 39 were in Aza and LDAC arms respectively). cCR was obtained in 39 patients (51.3%). ELN2017 risk was favorable in 8, intermediate in 15, and Adverse in 53. In 70 patients NK cell populations were analyzed (4 patients with very low percentage of NK cells, 2 with no sample at diagnosis were excluded from the study). There were significant differences between patients who achieve CRc and those who did not, according to DNAM-1 (74.4% vs 61.9, p=0.0018) and TACTILE (62% vs. 72%, p=0.02) expression on NK cells. The rest of antigens analyzed on NK cells were not significant. We found a cutoff of 62% of DNAM-1+ and less than 81% of TACTILE to differentiate populations in terms of survival using long-rank test. The number of DNAM-1 positive was 47 (60%) and TACTILE– was 55 (78%). The median OS of DNAM-1+ was better than DNAM-1− (18.4 vs 4.7 months, p=0.0001), and between TACTILE− vs TACTILE+ (17,36 vs. 4.6 months, p=0.005). Using an Cox model comparing karyotype, p53 and DNAM-1+ and TACTILE-, only DNAM-1+ was associated with better outcome (HR:0.33 (0.17-0.66) and TACTILE+ with worse (HR: 2.44 (1.20-4.99) in multivariate analysis.

Conclusions: DNAM-1(CD226) positive and TACTILE (CD96) negative NK cell populations are associated to CR and better OS. These findings need to be confirmed in larger studies. Interestingly, DNAM-1 is an activating receptor and TACTILE is an inhibitory receptor for NK cells that share the same CD155 ligand but display opposite function.

Disclosures: Bergua Burgues: Hospital San Pedro de Alcántara. Servicio de Hematologia. Cáceres. SPAIN: Current Employment; Daychii: Consultancy; Fundesalud. Grants of Europena funds.Daychii: Research Funding. Esteve: Abbvie: Consultancy; Jazz Pharmaceuticals: Consultancy, Research Funding; Astellas: Consultancy; Gilead: Consultancy; Pfizer: Research Funding; Kronos Bio: Research Funding. Ayala: Novartis: Consultancy, Speakers Bureau; Incyte: Consultancy; Astellas, BMS: Speakers Bureau. Martinez-Cuadron: Astellas: Consultancy, Speakers Bureau; Otsuka: Consultancy, Other: Travel, Accommodations; Pfizer: Other: Travel, Accommodations. Montesinos: Ryvu: Consultancy; Kura oncology: Consultancy; Astellas: Consultancy, Speakers Bureau; Novartis: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Menarini-Stemline: Consultancy, Research Funding; GILEAD: Consultancy; OTSUKA: Consultancy; BEIGENE: Consultancy; INCYTE: Consultancy; NERVIANO: Consultancy; Celgene: Consultancy; Janssen: Speakers Bureau; Jazz pharma: Consultancy, Research Funding, Speakers Bureau; Abbvie: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; BMS: Consultancy, Other, Research Funding; Daiichi Sankyo: Consultancy, Research Funding.

*signifies non-member of ASH