Fred Hutch at ASH: Latest CAR T data – BCMA, CD19, CD20 – plus new insights on transplantation, gene therapy – and more

The 61st American Society of Hematology Annual Meeting and Exposition will take place Dec. 7–10 in Orlando, Florida


For Immediate Release

Newswise — SEATTLE — Nov. 21, 2019 — Fred Hutchinson Cancer Research Center’s latest findings on CAR (chimeric antigen receptor) T-cell therapy, gene therapy, precision oncology, immune repair and transplantation will be featured at the 61st American Society of Hematology Annual Meeting and Exposition, which will be held Dec. 7–10 in Orlando, Florida.

Fred Hutch transplantation physician-scientist Dr. Stephanie Lee will become the new president of ASH at the end of the meeting, T-cell therapy pioneer Dr. Philip Greenberg will give the E. Donnall Thomas Lecture, and Dr. Andrew Cowan will present the latest on a new BCMA, or B-cell maturation antigen, CAR T-cell therapy for multiple myeloma. More details and other meeting highlights can be found below. All presentations will be held in the Orange County Convention Center.

Reporters requesting additional information or interviews, contact Molly McElroy who will be at the conference: mwmcelro@fredhutch.org, 206.941.8146 (cell).

IMMUNOTHERAPY

See preliminary results of a Phase 1 multiple myeloma trial with a CAR T-cell therapy combined with a repurposed Alzheimer’s drug, discussion of a new CD20 CAR T trial, plus various deep dives on the science of how CD19 CAR T-cell therapy works and how to improve it.

BCMA CAR T-CELL THERAPY / MULTIPLE MYELOMA

Efficacy and safety of fully human BCMA CAR T cells in combination with a gamma secretase inhibitor to increase BCMA surface expression in patients with relapsed or refractory multiple myeloma
Fred Hutch scientists are developing a novel immunotherapy approach for multiple myeloma, which involves a CAR T cell that targets BCMA proteins on multiple myeloma cells, plus a drug called a gamma secretase inhibitor, which increases the BCMA target on cancer cells. In an oral presentation, Dr. Andrew Cowan will present promising results from the first cohort of patients on the trial, all of whom responded to the treatment. The researchers published earlier findings of the trial in Blood in September.
Abstract No. 204 (oral presentation)
Saturday, Dec. 7, 1:15 p.m.
Valencia A (W415A), Level 4

Response to BCMA CART cells correlates with pretreatment target density and is improved by small-molecule inhibition of gamma secretase Dr. Damian Green will present findings from multiple myeloma patients that demonstrate a relationship between the number of BCMA targets on multiple myeloma cells and response to a BCMA-directed CAR T-cell therapy. The findings suggest that using a gamma secretase inhibitor to increase the amount of BCMAs on the cell surface could make CAR T work better. Abstract No. 1856 (poster presentation)
Saturday, Dec. 7, 5:307:30 p.m.
Hall B, Level 2

CD19 CAR T-CELL THERAPIES

With the success of CAR T-cell therapies for some blood cancers, Fred Hutch physician-scientists are taking a closer look to understand how patients respond to the therapy and what could be done to make the treatment work better.

Impact of Lisocabtagene Maraleucel (liso-cel) treatment on health-related quality of life and health utility in patients (pts) with relapsed/refractory (R/R) aggressive B-cell non-Hodgkin lymphoma (NHL): TRANSCEND NHL 001
Physician-scientist Dr. David Maloney will present findings from the TRANSCEND trial for CD19 CAR T that show how patients had improved quality-of-life measures (reduced fatigue and pain symptoms) starting six months after receiving CAR T-cell therapy. As medical director of the Cellular Immunotherapy Integrated Research Center at Fred Hutch, Maloney is at the forefront of clinical trials to develop cell therapies for blood and other cancers, including understanding side effects of CAR T’s and how to deliver them in outpatient settings. He cares for patients at the Bezos Family Immunotherapy Clinic at Seattle Cancer Care Alliance, the Hutch’s clinical-care partner.
Abstract No. 66 (poster presentation)
Saturday, Dec. 7, 8:45 a.m.
W308, Level 3

Factors associated with response, CAR T cell in vivo expansion, and progression-free survival after repeat infusions of CD19 CAR T cells
Does a second dose of CAR T cells help if the first doesn’t lead to a lasting remission? A team of Fred Hutch physician-scientists led by Dr. Cameron Turtle examined outcomes of 44 patients who received a second cycle of CD19 CAR T-cell immunotherapy for acute lymphoblastic leukemia, chronic lymphocytic leukemia or non-Hodgkin lymphoma. The type of chemotherapy given before the first infusion of CAR T cells and a higher dose of CAR T cells for the second infusion were associated with better outcomes.
Abstract No. 201 (oral presentation)
Saturday, Dec. 7, 12:30 p.m.
Valencia A (W415A), Level 4

Severe cytokine release syndrome is associated with impaired hematopoietic recovery after CD19-targeted CART-cell therapy
Dr. Krishna Juluri, a hematology-oncology fellow at Fred Hutch, will discuss how blood cells recover following CAR T treatment. The researchers found patients who experienced more severe cytokine release syndrome had slower recovery of blood counts. Since CRS can be treated, the Fred Hutch team concludes preventing it might improve blood-cell recovery.
Abstract No. 3229 (poster presentation)
Sunday, Dec. 8, 68 p.m.
Hall B, Level 2

Combination of NKTR-255, a polymer-conjugated human IL-15, with CD19 CAR T-cell immunotherapy in a preclinical lymphoma model
Dr. Cassie Chou will present preclinical studies that show how a novel IL-15 receptor agonist activates the interleukin 15 immune system pathway to enhance growth and anti-tumor efficacy of human CD19 CAR T cells in immunodeficient mice bearing human lymphoma. Future clinical trials will explore whether the compound can improve responses to CAR T-cell therapy. Chou is a research fellow and clinician who works in the lab of Dr. Cameron Turtle. Abstract No. 2866 (poster presentation)
Sunday, Dec. 8, 68 p.m.
Hall B, Level 2

Relapsed or refractory CLL after CD19-specific CART therapy: Treatment patterns and clinical outcomes
Treating high-risk chronic lymphocytic leukemia remains challenging with a 65% relapse rate following CAR T-cell therapy. Looking at outcomes of patients with progressive disease after CAR-T, Dr. Mazyar Shadman reports that CAR T-cell therapy did not work as well for patients who had already been treated with more than one other therapy for CLL. This study defines a benchmark for future trials that target relapsed CLL after CAR-T, and it also argues for referring patients to CAR T before they have exhausted other therapeutic options.
Abstract No. 4294 (poster presentation)
Monday, Dec. 9, 68 p.m.
Hall B, Level 2

CD20 CAR T-CELL THERAPY

CD20 targeted chimeric antigen receptor T cells for treatment of high-risk B-cell non-Hodgkin lymphomas
Most CAR T-cell therapies for blood cancers target a cancer-specific protein marker called CD19. But more targets are needed. Another CAR T-cell therapy that targets the CD20 protein on cancer cells is being developed by Fred Hutch scientists. Dr. Mazyar Shadman will give an overview of the trial, which is recruiting patients at the Hutch’s clinical-care partner, Seattle Cancer Care Alliance. Results of the trial are not ready and will not be reported at ASH.  
Abstract No. 3235 (poster presentation)
Sunday, Dec. 8, 68 p.m.
Hall B, Level 2

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TRANSPLANTATION

Extending the benefit of transplantation to more patients
Sirolimus combined with Cyclosporine (CSP) and Mycophenolate Mofetil (MMF) As graft-vs-host disease (GVHD) prophylaxis after nonmyeloablative (NMA) hematopoietic cell transplantation (HCT) using HLA Class I or Class II antigen mismatched donors: Results from a Phase II multicenter trial
Stem cell transplants can save lives, but their success depends on the availability of compatible donors. Unfortunately, depending upon ethnicity, fully HLA-matched donors cannot be found for 25-84% of patients. Dr. Brenda Sandmaier is presenting results from a Phase 2 trial that shows how a triple-drug combination improves outcomes for patients treated with mismatched donors.  
Abstract No. 369 (oral presentation)
Sunday, Dec. 8, 8 a.m.
W230, Level 2

Cord blood transplantation
Transplantation of blood stem cells from umbilical cord blood can treat blood disorders in patients who have been unable to find a suitable match among other donor sources. This is particularly true for patients of mixed ethnicities. Dr. Filippo Milano, associate director of Fred Hutch’s Cord Blood Program, is involved in the following presentations.

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GENE THERAPY

Scientists in the lab of Dr. Hans-Peter Kiem, director of Fred Hutch’s Stem Cell and Gene Therapy Program, are pioneering a variety of gene therapy approaches for HIV/AIDS, sickle cell anemia, blood cancers and other diseases. Below are their presentation abstracts.

Fully closed, large-scale, and clinical grade cell sorting of hematopoietic stem cell (HSC)-enriched CD90+ cells for transplantation and gene therapy
Dr. Stefan Radtke, a Fred Hutch staff scientist, will show for the first time in human blood samples how to isolate a rare stem cell subset that Fred Hutch researchers identified as capable of repopulating the entire blood and immune system. He used commercially available cell-sorting equipment to isolate the cells, an approach that has the potential to make gene therapy more efficient and affordable.
Abstract No. 3246 (poster presentation)
Sunday, Dec. 8, 68 p.m.
Hall B, Level 2

CRISPR/Cas9-mediated protection of normal hematopoiesis combined with the CD33/CD3 bispecific T-cell engager (BiTE) antibody AMG330 for improved AML therapy
CD33, a protein marker of cancerous cells in acute myeloid leukemia, is also found on healthy blood stem cells, which makes targeting CD33 toxic, as it kills both healthy cells and cancerous ones. Dr. Olivier Humbert, a staff scientist, used CRISPR to remove the CD33 target from healthy cells. Then, in a mouse model of acute myeloid leukemia, he found that T cells effectively use the CD33 bispecific T-cell engager (BiTE) antibody to attack cancer while sparing CRISPR-edited healthy cells.
Abstract No. 4427 (poster presentation)
Monday, Dec. 9, 68 p.m.
Hall B, Level 2
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PRECISION MEDICINE / PEDIATRIC AML

Researchers from the lab of Dr. Soheil Meshinchi, a pediatric oncologist and acute myeloid leukemia specialist, will present oral presentations that map genetic mutations to patient outcomes. He says the ongoing genomic profiling work can help guide targeted treatments for patients with AML, the deadliest leukemia among children and young adults.

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ASH NOTABLES

ASH E. Donnall Thomas Lecture and Prize
The long road to develop adoptive therapy for T cells that can effectively target acute myeloid leukemia and other malignancies
At the annual E. Donnall Thomas Lecture, Dr. Philip Greenberg, head of the Program in Immunology at Fred Hutch, will talk about how T cells have been engineered to target acute myeloid leukemia and our latest understanding of why cell therapies like CAR T-cell therapy work for some patients and not others, but can potentially be engineered to overcome these obstacles. ASH’s E. Donnall Thomas Lecture and Prize recognizes pioneering research achievements in hematology that have changed the field and is named for the Hutch’s Dr. E. Donnall Thomas, who received a Nobel Prize for his pioneering efforts in bone marrow transplantation. Thomas was also a colleague and mentor to Greenberg. Learn more about the lecture in an ASH news release.
Monday, Dec. 9, 910 a.m.
Hall D, Level 2

Incoming ASH President Dr. Stephanie Lee
ASH will recognize Dr. Stephanie Lee, a hematologist and transplant physician-scientist at Fred Hutch, as its new president at the society’s business meeting. Lee cares for stem cell transplant patients at the Hutch’s clinical-care partner, Seattle Cancer Care Alliance, and at UW Medicine. Her research aims to improve the lives of transplant recipients. Lee directs the Hutch’s Long-Term Follow-Up Research Program, which tracks the outcomes of more than 5,000 transplant survivors.
Tuesday, Dec. 10, 11:1511:30 a.m
Hall D, Level 2

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ON THE HORIZON / OTHER ABSTRACTS

Other notable experts and newsy topics at ASH:

Chronic myeloid leukemia: Meeting global need with better molecular testing
Dr. Jerald Radich is a medical oncologist who specializes in chronic myeloid leukemia, a relatively rare, slow-growing cancer that is fatal if left untreated. His Fred Hutch research lab examines the molecular genetics of leukemias in an effort to develop methods to improve the detection and treatment of the disease. At an ASH education session, Radich will talk about his award-winning collaboration with The Max Foundation, a Seattle-area nonprofit, which has led to more people in under-resourced areas being tested for CML. He will also give an oral presentation about a molecular test he developed that can predict which CML patients will have a sustained, deep molecular response to treatment.

Repairing immune function

Underappreciated by most, the thymus is a gland in the chest that acts like a boot camp for T cells, training them to identify and kill foreign invaders. The gland wears out with stress, infection and age, and finding ways to boost its productivity could help sustain human health. Researchers in the lab of Dr. Jarrod Dudakov, a Fred Hutch immunologist, will present the latest in understanding the signaling pathways of the thymus. Discovering master regulators could be targets for helping the thymus to repair itself. Below are their presentation abstracts.

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Note: Fred Hutch and its scientists who contributed to these discoveries may stand to benefit from their commercialization. See links above to ASH abstracts for more details on individual researchers’ disclosures.

The clinical trials referenced above involve investigational products and/or therapies that have not been approved for commercial marketing by the U.S. Food and Drug Administration or any other regulatory authority. Results may vary, and encouraging results from early-stage clinical trials may not be supported in later-stage clinical trials. No conclusions should be drawn from the information in this report about the safety, efficacy or likelihood of regulatory approval of these investigational products and/or therapies.

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Media Contact:
Molly McElroy
O: 206.667.2210
M: 206.941.8146
mwmcelro@fredhutch.org

At Fred Hutchinson Cancer Research Center, home to three Nobel laureates, interdisciplinary teams of world-renowned scientists seek new and innovative ways to prevent, diagnose and treat cancer, HIV/AIDS and other life-threatening diseases. Fred Hutch’s pioneering work in bone marrow transplantation led to the development of immunotherapy, which harnesses the power of the immune system to treat cancer. An independent, nonprofit research institute based in Seattle, Fred Hutch houses the nation’s first National Cancer Institute-funded cancer prevention research program, as well as the clinical coordinating center of the Women’s Health Initiative and the international headquarters of the HIV Vaccine Trials Network.

 

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