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899 Impact of Autologous Hematopoietic Cell Transplant (HCT) Followed By Dendritic Cell/Myeloma Fusion Vaccine with Lenalidomide Maintenance in Increasing Multiple Myeloma (MM) Immunity (BMT CTN 1401)

Program: Oral and Poster Abstracts
Type: Oral
Session: 653. Myeloma and Plasma Cell Dyscrasias: Clinical-Prospective Therapeutic Trials: Immune Therapy for Multiple Myeloma
Hematology Disease Topics & Pathways:
Clinical Trials, Translational Research, Clinical Research
Monday, December 13, 2021: 7:15 PM

David J. Chung, MD, PhD1, Nina Shah, MD2, Dina Stroopinsky3*, Juan WU4*, Lina Bisharat5*, Natalie S. Callander, MD6, Brent R. Logan, PhD7*, Kenneth C. Anderson, MD8,9,10, Thinle Chodon, MD11*, Meera Mohan, MD12,13, Steven Devine, MD14, Yvonne A. Efebera, MD, MPH15, Nancy Geller, PhD16*, Peiman Hematti, MD17, Leona A. Holmberg, MD, PhD18, Alan Howard, PhD19*, Bryon Johnson, PhD20, Hillard M Lazarus, MD21, Ehsan Malek, MD22, Philip L. McCarthy, MD23, David H. McKenna, MD24, Adam M. Mendizabal, MS25, Nikhil C. Munshi, MD, PhD26, Lynn O'Donnell, PhD27*, Aaron P. Rapoport, MD28, Ajay K. Nooka29, Jane Reese30*, Robert J. Soiffer, MD31, Lynne Uhl, MD32, Giulia Cheloni, PhD3*, Dimitra Karagkouni, PhD3*, Ioannis Vlachos, PhD3*, James W. Young, MD33, Jacalyn Rosenblatt, MD5, Edmund K. Waller, PhD, MD29, Marcelo C Pasquini, MD, MS34,35 and David Avigan, MD5,36

1Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
2University of California San Francisco, San Francisco, CA
3Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
4The Emmes Corporation, Rockville, MD
5Beth Israel Deaconess Medical Center, Boston, MA
6University of Wisconsin, Madison, WI
7Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI
8Jerome Lipper Multiple Myeloma Center, LeBow Institute for Myeloma Therapeutics, Dana-farber/Boston Children's Cancer and Blood Disorders Ctr, Boston, MA
9Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA
10The LeBow Institute for Myeloma Therapeutics, Dana-Farber Cancer Institute, Boston, MA
11Roswell Park, Buffalo, NY
12Medical College of Wisconsin, Milwaukee, WI
13Clinical Cancer Center, Division of Hematology Oncology, Medical College of Wisconsin, Milwaukee, WI
14National Marrow Donor Program, Minneapolis, MN
15Division of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH
16National Institutes of Health, Bethesda, MD
17Division of Hematology/Oncology, University of Wisconsin School of Medicine & Public Health, Madison, WI
18Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA
19Center for International Blood and Marrow Transplant Research, Manager, Immunobiology Research, Minneapolis, MN
20Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI
21Adult Hematologic Malignancies & Stem Cell Transplant Section, University Hospitals Cleveland Medical Center, Shaker Heights, OH
22Adult Hematologic Malignancies & Stem Cell Transplant Section, Seidman Cancer Center, University Hospitals Cleveland Medical Center, Cleveland, OH
23Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY
24Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN
25The Emmes Company, Rockville, MD
26Dana-Farber Cancer Institute, Harvard Medical School, Boston
27Comprehensive Cancer Center, Ohio State University Medical Center - James Cancer Hospital, Columbus, OH
28Division of Hematology and Oncology, University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD
29Winship Cancer Institute, Emory University, Atlanta, GA
30Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH
31Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
32Department of Pathology, Beth Israel Deaconess Med. Ctr., Boston, MA
33Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY
34CIBMTR® (Center for International Blood and Marrow Transplant Research), Department of Medicine,, Froedtert & The Medical College Cancer Ctr., Milwaukee, WI
35Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
36Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA

In a prior phase 2 study, personalized cancer vaccination with autologous dendritic cells (DCs) fused with primary MM tumor cells (DC/MM fusions) induced the expansion of circulating MM-reactive lymphocytes and was associated with conversion to complete response (CR) post-autoHCT in the absence of maintenance therapy.1 We now present a multicenter randomized phase II study that examined the efficacy of DC/MM fusion vaccination with lenalidomide maintenance therapy after autoHCT, compared with lenalidomide maintenance alone. The study offered a first-of-its-kind academic collaborative effort of personalized cell therapy using an open-source format, site-specific production, and centralized product characterization/release criteria verification.

Under the aegis of the BMT CTN (CTN 1401), 203 patients enrolled from 18 participating centers. Sixty-three patients dropped out of the study from enrollment to randomization for an overall dropout rate of 31%, concordant with the expected rate of 30% pre-specified in the protocol. Among the 140 patients, 68 were randomized to the vaccine arm, 37 to the lenalidomide/GM-CSF arm, and 35 to the lenalidomide alone arm. Ninety-one (65.0%) patients had high-risk MM. A collaborative process was established for the standardization of vaccine manufacturing including tumor cell harvest and cryopreservation, DC generation from leukapheresis collection, creation and quantification of the DC/tumor fusion vaccine, and the process of characterizing each cellular product. Of the 140 patients who underwent tumor collection, the median percentage of plasma cells in bone marrow aspirate differential was 45%. Mean CD86 expression and viability of the DC preparations were 80.6% and 79.3%, respectively. The mean fusion efficiency of the DC/MM product, as determined by co-expression of standard DC (CD86) and MM (CD38) markers, was 47.9%. Mean fusion cell viability was 78.6%. Vaccine was successfully generated for 63/68 patients (93%) assigned to the vaccine arm of the study.

Thirty-six of the 68 (52.9%) evaluable patients on the vaccine arm (80% confidence interval 44.5%, 61.3%) and 34 of the 68 (50.0%) of the non-vaccine arms (80% confidence interval 41.6%, 58.4%) achieved CR/sCR at 1-year post-transplant (p=0.3). Of the patients not achieving CR at time of randomization post-transplant, conversion to CR at 1-year was 34.8% for the vaccine arm and 27.3% for the non-vaccine arm (p=0.4). sCR/CR/VGPR at 1-year was achieved by 85.3% and 77.8% of patients on the vaccine and non-vaccine arms, respectively (p=0.2). The rates of post-transplant grade 3-4 toxicities were 76.5%, 62.5% for the vaccine, and non-vaccine arms, respectively (p=0.07). There were no grade 5 toxicities in any of the cohorts. The overall grade 2-3 infection rate was 22.9% (23.5% on the vaccine arm, 13.5% on the lenalidomide/GM-CSF arm, and 31.4% on the lenalidomide alone arm).

Quantification of circulating MM-reactive T cells was performed for an initial cohort of 20 patients who completed 1-year post-transplant assessments. Patients in the vaccine arm demonstrated a significant expansion of MM-reactive CD8 cells, representing 2.9%, 3.5%, and 15.9% of the lymphocyte population prior to post-transplant maintenance, following 1 cycle of lenalidomide and following 3 vaccinations at 1-year post-transplant, respectively (Figure). In contrast, there was no increase in MM-specific CD8 T cells in the control arm with levels of 1.1, 2.0. and 0.6, respectively. Single-cell transcriptomic analysis performed on the peripheral T-cell repertoire of 14 patients from the vaccine arm at serial time points demonstrated progressive expansion of dominant CD8, CD4, and NKT cell clones with an activated phenotype. Vaccination was associated with the recovery of T-cell clonal diversity.

This multicenter trial demonstrated successful site-specific production. DC/MM fusion vaccination with lenalidomide maintenance after autoHCT did not result in a significant increase in CR rates at 1-year but was associated with measurable anti-MM immune reactivity for which the impact on response duration will require longer term follow-up.

1. Rosenblatt, J. et al. Vaccination with dendritic cell/tumor fusions following autologous stem cell transplant induces immunologic and clinical responses in multiple myeloma patients. Clin. Cancer Res. 19, 3640–3648 (2013)

Disclosures: Shah: CareDx: Consultancy; GSK: Consultancy; Teneobio: Research Funding; Kite: Consultancy; Nektar: Research Funding; Poseida: Research Funding; Oncopeptides: Consultancy; Bluebird Bio: Research Funding; CSL Behring: Consultancy; Indapta Therapeutics: Consultancy; Janssen: Research Funding; Sanofi: Consultancy; Sutro Biopharma: Research Funding; Precision Biosciences: Research Funding; BMS/Celgene: Research Funding; Karyopharm: Consultancy; Amgen: Consultancy. Stroopinsky: The Blackstone Group: Consultancy. Anderson: AstraZeneca: Consultancy; Pfizer: Consultancy; Mana Therapeutics: Current holder of individual stocks in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy; Janssen: Consultancy; Oncopep: Current holder of individual stocks in a privately-held company, Membership on an entity's Board of Directors or advisory committees. Devine: Magenta Therapeutics: Current Employment, Research Funding; Tmunity: Current Employment, Research Funding; Johnsonand Johnson: Consultancy, Research Funding; Orca Bio: Consultancy, Research Funding; Be the Match: Current Employment; Sanofi: Consultancy, Research Funding; Vor Bio: Research Funding; Kiadis: Consultancy, Research Funding. Holmberg: Sanofi: Research Funding; Millennium-Takeda: Research Funding; Seattle Genetics: Research Funding; Bristol Myers Squibb: Research Funding; Merck: Research Funding; Janssen: Research Funding; Up-To-Date: Patents & Royalties. Johnson: Miltenyi Biotec: Research Funding. Lazarus: Bristol Myer Squibb: Membership on an entity's Board of Directors or advisory committees. Malek: Janssen: Other: Advisory board ; Medpacto Inc.: Research Funding; Takeda: Honoraria; BMS: Honoraria, Research Funding; Amgen: Honoraria; Cumberland Inc.: Research Funding; Bluespark Inc.: Research Funding; Sanofi: Other: Advisory Board. McCarthy: Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bluebird: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Juno: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Magenta Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. McKenna: Qihan Bio: Membership on an entity's Board of Directors or advisory committees; Fate Therapeutics: Other: all manufacturing of cell therapy products for clinical trials; Intima: Other: all manufacturing of cell therapy products for clinical trials; Gamida: Other: all manufacturing of cell therapy products for clinical trials; Magenta: Other: all manufacturing of cell therapy products for clinical trials. Munshi: Takeda: Consultancy; Novartis: Consultancy; Celgene: Consultancy; Oncopep: Consultancy, Current equity holder in publicly-traded company, Other: scientific founder, Patents & Royalties; Amgen: Consultancy; Janssen: Consultancy; Karyopharm: Consultancy; Abbvie: Consultancy; Adaptive Biotechnology: Consultancy; Legend: Consultancy; Pfizer: Consultancy; Bristol-Myers Squibb: Consultancy. Nooka: Janssen Oncology: Consultancy, Research Funding; Adaptive technologies: Consultancy; Sanofi: Consultancy; GlaxoSmithKline: Consultancy, Other: Travel expenses; Takeda: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy; Amgen: Consultancy, Research Funding; Oncopeptides: Consultancy; Karyopharm Therapeutics: Consultancy. Soiffer: Jazz Pharmaceuticals, USA: Consultancy; Precision Biosciences, USA: Consultancy; Juno Therapeutics, USA: Other: Data Safety Monitoring Board; Kiadis, Netherlands: Membership on an entity's Board of Directors or advisory committees; Rheos Therapeutics, USA: Consultancy; Gilead, USA: Other: Career Development Award Committee; NMPD - Be the Match, USA: Membership on an entity's Board of Directors or advisory committees; Jasper: Consultancy; Takeda: Consultancy. Uhl: Grifols: Consultancy, Speakers Bureau; Abbott: Consultancy, Speakers Bureau; UpToDate: Patents & Royalties. Young: Amgen: Current equity holder in publicly-traded company; Pfizer: Current equity holder in publicly-traded company; Merck: Current equity holder in publicly-traded company. Rosenblatt: Attivare Therapeutics: Consultancy; Bristol-Myers Squibb: Research Funding; Parexel: Consultancy; Wolters Kluwer Health: Consultancy, Patents & Royalties; Imaging Endpoints: Consultancy; Karyopharm: Membership on an entity's Board of Directors or advisory committees. Waller: Verastem Oncology: Consultancy, Research Funding; Cambium Oncology: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Pasquini: GlaxoSmithKline: Research Funding; Kite Pharma: Research Funding; Novartis: Research Funding; Bristol Myers Squibb: Consultancy, Research Funding. Avigan: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding; Kite Pharma: Consultancy, Research Funding; Juno: Membership on an entity's Board of Directors or advisory committees; Partner Tx: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Aviv MedTech Ltd: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Legend Biotech: Membership on an entity's Board of Directors or advisory committees; Chugai: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; Parexcel: Consultancy; Takeda: Consultancy; Sanofi: Consultancy.

OffLabel Disclosure: Dendritic Cell/Tumor Fusion Vaccine and GM-CSF

*signifies non-member of ASH