Newswise — SEATTLE — Nov. 30, 2023 — The 65th Annual Meeting & Exposition of the American Society of Hematology (ASH) will take place in San Diego, Calif. and online Dec. 9-12.
Below are highlights of Fred Hutchinson Cancer Center research to be presented and experts available to comment on news. You can follow Fred Hutch on social media for additional updates and check out Fred Hutch booth #3337 in the exhibit hall.
Gene therapies for sickle cell disease
Gene therapies to treat sickle cell disease are making their way through U.S. Food and Drug Administration approvals. Sickle cell affects millions of people worldwide and an estimated 100,000 people in the United States, according to the Centers for Disease Control and Prevention. The inherited blood disorder is caused by a single nucleotide change on the beta-globin gene. This one mutation creates sickle-shaped blood cells instead of round cells and leads to a lifetime of treatments for people suffering from the disease.
Fred Hutch has a range of experts available to comment on sickle cell:
CAR T-cell therapy
Poster presentation: Efficacy and safety of a third-generation CD20 CAR-T (MB-106) for treatment of relapsed/refractory indolent B-cell non-Hodgkin lymphoma: Phase-1 results from a multicenter trial Abstract: 2102 Presenter: Mazyar Shadman, MD, MPH (follow: @mshadman) Saturday, Dec. 9, 5:30-7:30 p.m. Halls G-H, San Diego Convention Center
In a poster presentation on this phase 1, multicenter study, Mazyar Shadman, MD, MPH, study chair, who holds the Innovators Network Endowed Chair at Fred Hutch, will the latest findings on a third-generation CD20 CAR T-cell therapy, which was initially developed at Fred Hutch and exclusively licensed to Mustang Bio, Inc. The research team found that treatment with MB-106 resulted in complete responses and CAR-T persistence in patients with indolent B-cell non-Hodgkin lymphomas.
Oral presentation: Autologous transplant (auto-HCT) is associated with improved clinical outcomes compared to CAR-T therapy in patients (pts) with large B-cell lymphoma (LBCL) achieving a complete remission Abstract: 781 Presenter: Mazyar Shadman, MD, MPH (follow: @mshadman) Monday, Dec. 11, 10:30 a.m. Pacific Ballroom Salons 18-19, Marriot Marquis, San Diego
Fred Hutch blood cancer specialist and study author Mazyar Shadman, MD, MPH, will present findings that show patients with relapsed large B-cell lymphoma who achieve a complete remission from being treated with autologous transplant have a lower relapse rate and improved progression-free survival compared to those treated with CAR-T therapy. These findings are in line with clinical outcomes reported in 2022 in the journal Blood.
Multiple myeloma
Multiple myeloma is currently considered incurable, and regular treatment regimens requiring patients to come into the clinic or get frequent bloodwork are generally required even for patients in remission. Fred Hutch multiple myeloma expert Rahul Banerjee, MD, FACP, is committed to improving the patient experience for people being treated for multiple myeloma. He’s particularly interested in a trending topic of “time toxicity,” or how much time patients have to spend dealing with their disease. Banerjee will present studies on simpler but just as effective multiple myeloma treatment regimens that aim to minimize time toxicity for patients.
Poster presentation: Financial toxicity and time toxicity in multiple myeloma: Prevalence, predictors and impact on QOL Abstract: 2386 Presenter: Rahul Banerjee, MD, FACP (follow: @RahulBanerjeeMD) Saturday, Dec. 9, 5:30-7:30 p.m. Halls G-H, San Diego Convention Center
Patients with multiple myeloma are at ongoing risk of financial toxicity from medication costs and lost productivity and time toxicity from ongoing monitoring and supportive care even into the maintenance phase. These toxicities may negatively impact patient quality of life. In a large survey of multiple myeloma patients, 20% to 25% reported financial toxicity regardless of their disease status. Even for patients in remission on maintenance therapy, almost 40% reported time toxicity. Further research is ongoing to understand ways to lower both financial and time toxicity.
Oral presentation: Impact of dexamethasone (dex) dose strength on outcomes in newly diagnosed multiple myeloma (NDMM): A secondary analysis of SWOG studies S0777 and S1211 Abstract: 1066 Presenter: Rahul Banerjee, MD, FACP (follow: @RahulBanerjeeMD) Monday, Dec. 11, 5:15 p.m. Marriott Grand Ballroom 2-4, Marriot Marquis San Diego
Chronic corticosteroids such as dexamethasone have been a common component of multiple myeloma treatments. But steroids can make patients anxious and jittery and cause them to gain weight and lose sleep. Fred Hutch’s Banerjee and Fred Hutch’s Andrew Cowan, MD, clinical director of Fred Hutch’s myeloma service, wondered earlier this year how important full-dose dex was in the era of modern targeted therapies. They worked with SWOG Cancer Research Network to examine data from more than 500 multiple myeloma patients who received treatment in two large clinical trials. They found that patients with reduced dex doses had similar lengths of remission and overall survival compared to patients who received a full dose of dex. Banerjee hopes the findings lead to future studies that use lower starting doses of dex or that build in dex dose decreases after a few months of treatment.
Poster presentation: Standard-of-care bortezomib dosing in multiple myeloma: An international survey of physicians Abstract: 5073 Presenter: Rahul Banerjee, MD, FACP (follow: @RahulBanerjeeMD) Monday, Dec. 11, 6-8 p.m. Halls G-H, San Diego Convention Center
In the past decade, an important gap has emerged in how physicians use the injectable drug bortezomib as part of treatment for multiple myeloma. Clinical trials use twice-per-week dosing, but it has been suspected that once-per-week dosing would be just as effective and preferred. Banerjee and colleagues from an international consortium evaluated this standard of care in a survey of physicians caring for multiple myeloma patients. They compiled survey responses from more than 200 physicians in 38 countries and found that the once-per-week dosing was preferred. Banerjee believes this study will pave the way for future studies to switch to once-per-week dosing, which has fewer side effects for patients and would mean less time in the clinic to receive the treatment. Blood Cancer Journal published the findings Nov. 6. Banerjee is also co-first author of a large real-world analysis on this topic being presented in an ASH oral presentation (Abstract 544).
Transplantation
As a world leader in developing transplantation for blood diseases, Fred Hutch has a long history in making this curative approach safe and effective. Continued work examines what makes a “perfect” graft between donated cells and their recipient and how to expand the treatment so that more people can benefit. At ASH, Fred Hutch stem cell transplantation experts will present a variety of studies on immunology, cord blood and age-related donor factors.
Oral presentation: MAIT cell frequencies within PBSC grafts are associated with donor CMV serostatus and age: An initial analysis from the DKMS and NMDP graft composition study Abstract: 1033 Presenter: Kate Markey, MBBS, PhD, FRACP Monday, Dec. 11, 4:30 p.m. Room 6DE, San Diego Convention Center
What is an ideal stem cell graft that successfully treats the disease with minimal side effects? Fred Hutch physician-scientist Kate Markey, MBBS, PhD, FRACP, will present preliminary findings from an international project that’s examining 2,000 transplant graft products from cancer centers in the U.S. and Germany. The project aims to determine which donor-recipient combinations yield the best patient outcomes, including characteristics about the microbiome and immune system, which is Markey’s expertise. “Ideally we will learn new information about what represents the ‘perfect’ type of graft to be giving patients, and hopefully this leads to new approaches to modifying graft products that are infused into patients,” Markey said. The research team is looking for collaborative partners to expand the research.
Oral presentation: Combined effect of unrelated donor age and HLA peptide-binding motifs (PBM) match status on HCT outcomes Abstract: 1045 Presenter: Rohtesh Mehta, MD, MPH, MS Monday, Dec. 11, 4:30 p.m. Ballroom 20CD, San Diego Convention Center
Ongoing clinical studies are revealing how to improve blood stem cell transplants for people with blood disorders, which would help make the treatment available to more people who need it. Rohtesh Mehta, MD, MPH, MS, is a Fred Hutch hematologist and blood and marrow transplant physician-scientist. At ASH, Mehta will present data on how transplantations from younger donors (35 years old and younger) led to improved outcomes when compared with older donors. The data also show how younger donors with inferior matching with the transplant recipient led to about the same outcomes as older donors with better matching. These findings are important toward widening the pool of potential matches for stem cell recipients. Mehta also studies how to better manage and prevent graft-vs.-host disease in stem cell patients and has another oral presentation (Abstract 236) on those findings.
Oral presentation: Infusion of UM171-expanded cord blood led to excellent survival in patients with high-risk leukemias: Results from two independent phase II studies Abstract: 1040 Presenter: Filippo Milano, MD, PhD Monday, Dec. 11, 4:45 p.m. Ballroom 20 AB, San Diego Convention Center
Stem cells in cord blood can be a valuable donor source for patients who do not have a suitable match from other sources. But some cord blood transplant recipients experience a delay in recovery after transplantation or ultimately relapse. A small molecule called UM171 could help. Filippo Milano, MD, PhD, director of Fred Hutch’s Cord Blood Transplant Program, will present data from 52 patients with high-risk leukemias enrolled in two independent prospective studies conducted between 2019 and 2022. “About 70% of patients survived at two years post-transplant with no evidence of disease recurrence,” Milano said. “These outcomes are incredibly positive if we consider that 30% of the patients did not see a benefit from previous stem cell transplantation and that 20% of the entire population presented with a genetic mutation in the tp53 gene which is usually associated with very dismal outcomes.” The team is now planning a larger randomized study to test this approach versus conventional stem cell transplantation approaches.
Thymus
The often-overlooked thymus is a small gland in the chest where disease-killing T cells of the immune system develop their capabilities. The thymus can repair itself, but it wears out with age, stress and infection. Scientists in the Fred Hutch lab of Jarrod Dudakov, PhD, (follow @dudakov_lab) are studying how to boost thymic regeneration to help boost immunity in patients undergoing thymus-damaging cancer treatments or people who are do not see the full immune benefit from vaccines due to being immunocompromised. The team will report their latest findings at ASH.
Oral presentation: Hematopoietic stem cell transplantation (HCT) conditioning leads to NK cell cytotoxicity limiting endogenous thymus regeneration Abstract: 461 Presenter: David Granadier, BS Sunday, Dec. 10, 10:30 a.m. Room 6B, San Diego Convention Center
Poster presentation: Testing the limits of endogenous thymic regeneration after HCT conditioning Abstract: 3427 Presenter: Dante Dennis Acenas II Sunday, Dec. 10, 6-8 p.m. Halls G-H, San Diego Convention Center
Poster presentation: Zinc status affects T cell reconstitution in patients receiving naïve T cell depleted allogeneic HSCT Abstract: 3562 Presenter: Lorenzo Iovino, MD, PhD Sunday, Dec. 10, 6-8 p.m. Halls G-H, San Diego Convention Center
Translational science
Other notable Fred Hutch ASH presentations in preclinical models:
Oral presentation: BCMA-directed low- dose alpha-emitter therapy eliminates minimal residual disease in a multiple myeloma mouse xenograft model Abstract: 53 Presenter: Damian Green, MD Saturday, Dec. 9, 10:30 a.m. Grand Hall D, Manchester Grand Hyatt San Diego
The protein B-cell maturation antigen (BCMA) found almost exclusively on multiple myeloma cells continues to be studied as a way to target and kill the diseased cells. But despite advances with CAR T cells and bispecific antibodies, almost all patients ultimately relapse after treatment with BCMA-targeting therapies. This is likely because the treatment does not eliminate all the cancerous cells, allowing some to grow back. Damian Green, MD, a multiple myeloma expert, will present work on behalf of a Fred Hutch team that has been developing approaches to improve BCMA therapies. Green, who is also a radioimmunotherapy expert, will present the team’s findings that attaching a radioactive molecule to a BCMA antibody protein eliminated human multiple myeloma tumor cells growing in a mouse model. In some studies, 100% of the mice with multiple myeloma remained free of the disease for at least 150 days. The team is continuing to investigate the approach in preclinical models and translating the findings into human clinical trials.
Oral presentation: Microbiota-specific T cells contribute to graft-versus-host disease after allogeneic stem cell transplantation Abstract: 345 Presenter: Albert Yeh, MD Saturday, Dec. 9, 4:30 p.m. Room 7, San Diego Convention Center
As a Fred Hutch physician, Albert Yeh, MD, cares for people undergoing bone marrow transplantation, and as a researcher he’s studying how T cells of the immune system underlie the success of the treatment. Graft-vs.-host disease (GVHD) is a side effect of transplantation that occurs when donated cells meant to cure the disease attack the transplant recipient. It’s currently thought that GVHD develops due to genetic mismatching between donor and recipient. However, at ASH, Yeh will discuss his preclinical research on how donated T cells cause GVHD based on a transplant recipient’s microbiome as well as genetic mismatching with the donor.
Poster presentation: CD90-targeted cocal-pseudotyped lentivirus as a robust platform for human HSC gene therapy Abstract: 2254 Presenter: Justin Thomas Saturday, Dec. 9, 5:30-7:30 p.m. Halls G-H, San Diego Convention Center
Gene therapies for blood disorders such as sickle cell disease and HIV are a promising way to treat chronic diseases. But the process is cumbersome. It requires specialized facilities and clinical staff to remove cells from patients’ bodies, gene edit the cells outside of the body and then reinfuse the cells — a process called ex vivo gene editing. Scientists in the Fred Hutch lab of Hans-Peter Kiem, MD, PhD, are focused on making gene therapies easier to deliver to patients by having the technology delivered in vivo, through an injection. At ASH, Justin Thomas, a graduate student in the Kiem lab, will present a new way to deliver in vivo gene edits to specific blood stem cells that shows in preclinical models 5 to 10 times greater effectiveness than existing methods.
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Note: To the extent any commercializable discoveries result from the aforementioned research, Fred Hutch and the scientists who contributed to the discoveries may stand to benefit from their future commercialization.
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 Tip Sheet or from the conference presentations about the safety, efficacy or likelihood of regulatory approval of these investigational products and/or therapies.
Fred Hutch does not endorse or verify the accuracy of any content of any third party sites, materials or related information that may be referenced by the presentations.
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Fred Hutchinson Cancer Center unites individualized care and advanced research to provide the latest cancer treatment options while accelerating discoveries that prevent, treat and cure cancer and infectious diseases worldwide.
Based in Seattle, Fred Hutch is an independent, nonprofit organization and the only National Cancer Institute-designated cancer center in Washington. We have earned a global reputation for our track record of discoveries in cancer, infectious disease and basic research, including important advances in bone marrow transplantation, immunotherapy, HIV/AIDS prevention and COVID-19 vaccines. Fred Hutch operates eight clinical care sites that provide medical oncology, infusion, radiation, proton therapy and related services. Fred Hutch also serves as UW Medicine’s cancer program.
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