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4256 Randomized Phase II Trial of Dendritic Cell/AML Fusion Cell Vaccination Compared to Standard of Care Therapy in AML CR1

Program: Oral and Poster Abstracts
Session: 616. Acute Myeloid Leukemias: Investigational Drug and Cellular Therapies: Poster III
Hematology Disease Topics & Pathways:
Research, Clinical trials, Acute Myeloid Malignancies, AML, Translational Research, Clinical Research, Diseases, Immunology, Biological Processes, Myeloid Malignancies
Monday, December 9, 2024, 6:00 PM-8:00 PM

Prateek Pophali, MBBS1, Giulia Cheloni, PhD2*, Richard M. Stone, MD3, Kai W Wucherpfennig, MD, PhD4*, Aric C. Hall, MD5*, Amir T. Fathi, MD6, Lina Bisharat, MS2*, Emma K Logan7*, Yiwen Liu, MS8*, Donna S. Neuberg, ScD9, Malgorzata McMasters, MD10, Jessica Liegel, MD2, Jacqueline S. Garcia, MD11, Daniel J. DeAngelo, MD, PhD11, Michele Narcis10*, Dina Stroopinsky, PhD12*, Pavania Elavalakanar, MSc, BSc7*, Ioannis S Vlachos, PhD7*, Ilene A. Galinsky, MSN, ANP-C11, Jason Pyrdol13*, Georges Chedid, MD14*, Dimitra Karagkouni, PhD15*, Shivani Nanda16*, Kathrine S Rallis, MBBS, MSc17, Isabella Saldarriaga, BS18*, Hazal Toros, MS2*, Haitham Abdelhakim, MD19, Amelia Langston, MD20, Joseph P. McGuirk, DO21, Donald Kufe, MD4*, David Avigan, MD18 and Jacalyn Rosenblatt, MD18

1Beth Israel Deaconess Medical Center, FRAMINGHAM, MA
2Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
3Dana-Farber Cancer Institute, Boston, MA
4Dana Farber Cancer Institute, Harvard Medical School, Boston, MA
5Department of Medicine Division of Hematology, Medical Oncology and Palliative Care, University of Wisconsin–Madison, Madison, WI
6Massachusetts General Hospital, Boston, MA
7Beth Israel Deaconess Medical Center, Boston, MA
8Data Science, Dana-Farber Cancer Institute, Boston, MA
9Department of Data Science, Dana-Farber Cancer Institute, Boston, MA
10Beth Israel Deaconess Medical Center, Boston
11Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
12Takeda Oncology, Boston
13Dana-Farber Cancer Insitute, Boston, MA
14Mount Auburn Hospital, Cambridge
15Department of Pathology, Cancer Research Institute, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA
16Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA
17Beth Israel Deaconess Medical Center, Harvard Medical School, Brookline, MA
18Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA
19Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Cancer Center, Westwood, KS
20Emory University, Winship Cancer Institute, Atlanta, GA
21Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Kansas City, KS

Introduction: We have developed a personalized cancer vaccine in which patient derived AML cells are fused with autologous dendritic cells (DCs), presenting a broad array of antigens including shared and neoantigens. Here we report the results of the multicenter randomized phase II clinical trial (NCT03059485) of DC/AML fusion cell vaccination in AML patients who achieve a remission following chemotherapy or HMA/Venetoclax.

Methods: Eligible patients were >55 years and were not candidates for allogeneic transplantation. The primary endpoint was to assess 2-year progression free survival. Leukemia cells were collected and cryopreserved at time of disease presentation. Patients underwent standard of care remission induction therapy, with either 7+3 or HMA/Ven, at the discretion of the treating physician. Patients in CR (CR/CRi) were randomized 2:1 to the vaccine (Arm A) or standard of care arm (Arm C). Arm B, vaccine with PD-1 blockade, was removed prior to any patient being treated. Patients in Arm C could receive maintenance therapy, while those in Arm A did not. Patients in Arm A underwent leukapheresis and DCs were generated by cytokine mediated differentiation. DC/AML fusions were created by co-culture of DCs and leukemia cells in the presence of polyethylene glycol. The trial was designed with a target accrual of 75 patients but closed to prematurely due to slow enrollment during COVID-19 and changes in standard of care leukemia therapy including maintenance HMA/Ven and IDH/FLT3 inhibitors. Herein, we report the results of 41 randomized patients. This trial is not powered to detect difference in clinical endpoints.

Results: 41 patients with median age 68 years (range 55-86) were randomized, 27 to Arm A and 14 to Arm C. Two patients (one in each arm) withdrew consent and were not followed for response or survival. Additionally, In Arm A, 1 patient had disease progression, 1 proceeded to allogeneic transplantation, 1 had autoimmune hepatitis and were considered ineligible to proceed with vaccine generation. Fusion vaccine was successfully generated in 23 patients, with a mean fusion efficiency of 50.73%, and a viability of 75%.

2-year PFS in arm A was 31% by intention to treat and 36% in vaccinated patients (N=22) compared to 23% in arm C (N=13). 2-year OS was 73% in Arm A and 61% in Arm C. 2 grade-2 injection site reactions, 2 grade-2 and 1 grade-3 platelet count decrease were attributable to vaccine.

Immune response was characterized by interferon gamma (IFN) secretion following ex-vivo exposure to autologous tumor lysate. A mean of 1.5-fold increase in the IFN+ CD4+ T cells and 1.85-fold in the IFN+ CD8+ T cells was observed following vaccination (pre-vaccine 1 compared to peak post-vaccination, n=19). Deep TCR repertoire sequencing of serial blood and bone marrow samples was performed from pre- and post-vaccination timepoints for four patients. These longitudinal data were used to identify T cell clonotypes that significantly increased following vaccination. Two major classes of treatment-expanded clonotypes were identified: pre-existing clonotypes that increased following vaccination and emergent clonotypes only detected following vaccination. Comparison of 3- and 6-month follow up blood samples demonstrated persistence of all emergent clones.

Conclusion: In summary, DC/AML fusion vaccination in older patients in CR1 in the absence of maintenance therapy resulted in a 2-year PFS of 36% and OS of 73%. Immunologic response was characterized by emergence and persistence of specific T cell clonotypes. Ongoing studies include analyzing expanded T cell clones as a means for antigen discovery and evaluation of DC/AML vaccination following allogeneic transplant. Future directions include the potential to develop a novel combinatorial approach to maintenance therapy, by incorporating DC/AML fusion cell vaccination to HMA and targeted therapy based maintenance therapy for AML.

Disclosures: Stone: Epizyme Inc: Consultancy, Other: consulting fees; DAVA Oncology: Consultancy, Other: consulting fees; Actinium Pharmaceuticals, Inc.,: Consultancy, Other: consulting fees; AbbVie: Consultancy, Other: consulting fees; Celularity: Consultancy, Other: consulting fees; CTI BioPharma: Consultancy, Other: consulting fees; Takeda Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: consulting fees; Syntrix Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: consulting fees; Amgen: Consultancy, Other: consulting fees; Aptevo Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: consulting fees; AROG Pharmaceuticals: Consultancy, Other: consulting fees; AvenCell: Consultancy, Other: consulting fees; BerGenBio: Consultancy, Other: consulting fees; Bristol Myers Squibb: Consultancy, Other: consulting fees; Boston Scientific: Consultancy, Other: consulting fees; Janssen: Consultancy, Other: consulting fees; GSK: Consultancy, Other: consulting fees; Syros Pharmaceuticals: Consultancy, Other: consulting fees; Ligand Pharmaceuticals: Consultancy, Other: consulting fees; Novartis: Consultancy, Other: consulting fees; Rigel Therapeutics, Inc.: Consultancy, Other: consulting fees; Hemavant Sciences: Consultancy, Other: consulting fees; LAVA Therapeutics: Consultancy, Other: consulting fees; Jazz Pharmaceuticals: Consultancy, Other: consulting fees; Kura Oncology: Consultancy, Other: consulting fees. Wucherpfennig: Fate Therapeutics: Research Funding; Novartis: Research Funding; Immunitas Therapeutics: Other: Co-founder; Nextechinvest: Membership on an entity's Board of Directors or advisory committees; D2M Biotherapeutics: Membership on an entity's Board of Directors or advisory committees; Solu Therapeutics: Membership on an entity's Board of Directors or advisory committees; DEM BioPharma: Membership on an entity's Board of Directors or advisory committees; TScan therapeutics: Current equity holder in publicly-traded company. Fathi: Abbvie: Consultancy, Research Funding; Astellas: Consultancy; Agios: Ended employment in the past 24 months; Pfizer: Consultancy; Rigel: Consultancy; Remix: Consultancy; Amgen: Consultancy; Daiichi Sankyo: Consultancy; Bristol Myers Squibb: Consultancy, Research Funding; Autolus: Consultancy; ImmunoGen: Consultancy; Mablytics: Consultancy; Genentech: Honoraria; Ispen: Consultancy; Novartis: Consultancy; Kite: Consultancy; Foghorn, Blueprint Medicines, Kura, Trillium: Honoraria; AbbVie, BMS/Celgene, and Agios/Servier: Research Funding; Ipsen: Consultancy; EnClear: Consultancy; BMS/Celgene: Consultancy; PureTech: Consultancy; Takeda: Consultancy; Forma: Consultancy; Servier: Consultancy, Research Funding; MorphoSys: Consultancy; AstraZeneca: Honoraria; Gilead: Consultancy; Menarini Group: Consultancy; Orum: Consultancy. Neuberg: Madrigal Pharmaceutical: Current equity holder in publicly-traded company. Liegel: Beth Israel Deaconess Medical Center: Current Employment; Seagen: Research Funding; Janssen: Research Funding; Novartis: Research Funding. Garcia: Newave: Research Funding; Servier: Consultancy; Taiho: Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Research Funding. DeAngelo: Incyte: Consultancy; Jazz: Consultancy; Kite: Consultancy; Novartis: Consultancy, Research Funding; Pfizer: Consultancy; Servier: Consultancy, Honoraria, Research Funding; Takeda: Consultancy; Bristol-Meyers Squibb: Honoraria; Abvie: Research Funding; Glycomimetics: Research Funding; Daiichi-Sankyo: Other: DSMB; Fibrogen: Other: DSMB; MT Sinai MPN Consortium: Other: DSMB; Gilead: Consultancy; Curis: Consultancy; Blueprint: Consultancy, Research Funding; Autolos: Consultancy; Amgen: Consultancy, Honoraria. Stroopinsky: Takeda: Current Employment. Vlachos: Harvard Stem Cell Institute: Research Funding; NIDDK: Research Funding; Guidepoint Global: Consultancy; NCI: Research Funding; NHLBI: Research Funding; Mosaic: Consultancy. Abdelhakim: Iovance Biotherapeutics: Research Funding. McGuirk: Legend biotech: Consultancy; Sana technologies: Consultancy; Caribou bio: Consultancy; BMS: Consultancy; CRISPR therapeutics: Consultancy; NEKTAR therapeutics: Consultancy; Autolus: Consultancy; Envision: Consultancy; Allo Vir: Consultancy; Novartis: Consultancy; Kite: Consultancy. Avigan: Kite, a Gilead Company: Research Funding; Pharmacyclics: Research Funding; Celgene: Consultancy, Other: Advisory Role, Research Funding; Kowa Pharmaceutical: Consultancy, Other: Advisory Board; Takeda: Consultancy, Other: Advisory Role; Chugai Pharma: Consultancy, Other: Advisory Role; Paraxel: Current Employment; Sanofi: Consultancy, Other: Advisory Board; Kite/Gilead: Consultancy, Other: Advisory Role, Research Funding; Janssen: Consultancy, Other: Advisory Board; Bristol Myers Squibb: Consultancy, Other: Advisory Board; Karyopharm Therapeutics: Consultancy, Other: Advisory Role; Partners Therapeutics: Consultancy, Other: Advisory Board; Aviv Med Tech: Consultancy, Other: Advisory Board; Legend Biotech: Consultancy, Other: Advisory Role; Juno Therapeutics: Consultancy, Other: Advisory Role. Rosenblatt: Janssen Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Karyopham therapeutics: Other: DSMB; Parexel/Calyx: Consultancy, Other: blinded adjudicator for clinical trial data; Clario (BioClinica): Consultancy, Other: blinded adjudicator for clinical trial data; Sanofi: Research Funding; Bristol myers squibb: Research Funding; Attivare therapeutics: Consultancy; KITE: Membership on an entity's Board of Directors or advisory committees; USPTO: Patents & Royalties: US patent no. 11, 026,921, .

*signifies non-member of ASH