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Tag: Fred Hutchinson Cancer Center

  • How Bad Could BA.2.86 Get?

    How Bad Could BA.2.86 Get?

    Since Omicron swept across the globe in 2021, the evolution of SARS-CoV-2 has moved at a slower and more predictable pace. New variants of interest have come and gone, but none have matched Omicron’s 30-odd mutations or its ferocious growth. Then, about two weeks ago, a variant descended from BA.2 popped up with 34 mutations in its spike protein—a leap in viral evolution that sure looked a lot like Omicron. The question became: Could it also spread as quickly and as widely as Omicron?

    This new variant, dubbed BA.2.86, has now been detected in at least 15 cases across six countries, including Israel, Denmark, South Africa, and the United States. This is a trickle of new cases, not a flood, which is somewhat reassuring. But with COVID surveillance no longer a priority, the world’s labs are also sequencing about 1 percent of what they were two years ago, says Thomas Peacock, a virologist at the Pirbright Institute. The less surveillance scientists are doing, the more places a variant could spread out of sight, and the longer it will take to understand BA.2.86’s potential.

    Peacock told me that he will be closely tracking the data from Denmark in the next week or two. The country still has relatively robust SARS-CoV-2 sequencing, and because it has already detected BA.2.86, we can now watch the numbers rise—or not—in real time. Until the future of BA.2.86 becomes clear, three scenarios are still possible.

    The worst but also least likely scenario is another Omicron-like surge around the world. BA.2.86 just doesn’t seem to be growing as explosively. “If it had been very fast, we probably would have known by now,” Peacock said, noting that, in contrast, Omicron’s rapid growth took just three or four days to become obvious.

    Scientists aren’t totally willing to go on record ruling out Omicron redux yet, if only because patchy viral surveillance means no one has a complete global picture. Back in 2021, South Africa noticed that Omicron was driving a big COVID wave, which allowed its scientists to warn the rest of the world. But if BA.2.86 is now causing a wave in a region that isn’t sequencing viruses or even testing very much, no one would know.

    Even in this scenario, though, our collective immunity will be a buffer against the virus. BA.2.86 looks on paper to have Omicron-like abilities to cause reinfection, according to a preliminary analysis of its mutations by Jesse Bloom, a virologist at the Fred Hutchinson Cancer Center, in Washington, but he adds that there’s a big difference between 2021 and now. “At the time of the Omicron wave, there were still a lot of people out there that had never been either vaccinated or infected with SARS-CoV-2, and those people were sort of especially easy targets,” he told me. “Now the vast, vast majority of people in the world have either been infected or vaccinated with SARS-CoV-2—or are often both infected and vaccinated multiple times. So that means I think any variant is going to have a very hard time spreading as well as Omicron.”

    A second and more likely possibility is that BA.2.86 ends up like the other post-Omicron variants: transmissible enough to edge out a previous variant, but not transmissible enough to cause a big new surge. Since the original Omicron variant, or BA.1, took over, the U.S. has successively cycled through BA.2, BA.2.12.1, BA.5, BQ.1, XBB.1.5—and if these jumbles of numbers and letters seem only faintly familiar, it’s because they never reached the same levels of notoriety as the original. Vaccine makers track them to keep COVID shots up to date, but the World Health Organization hasn’t deemed any worthy of a new Greek letter.

    If BA.2.86 continues to circulate, though, it could pick up mutations that give it new advantages. In fact, XBB.1.5, which rose to dominance earlier this year, leveled up this way. When XBB.1.5’s predecessor was first identified in Singapore, Peacock said, it wasn’t a very successful variant: Its spike protein bound weakly to receptors in human cells. Then it acquired an additional mutation in its spike protein that compensated for the loss of binding, and it turned into the later-dominant XBB.1.5. Descendents of BA.2.86 could eventually become more transmissible than the variant looks right now.

    A third scenario is that BA.2.86 just fizzles out and goes away. Scientists now believe that highly mutated variants such as BA.2.86 are probably products of chronic infections in immunocompromised patients. In these infections, the virus remains in the body for a long time, trying out new ways to evade the immune system. It might end up with mutations that make its spike protein less recognizable to antibodies, but those same mutations could also render the spike protein less functional and therefore the virus less good at transmitting from person to person.

    “Variants like that have been identified over the last few years,” Bloom said. “Often there’s one sample found, and that’s it. Or multiple samples all found in the same place.” BA.2.86 is transmissible enough to be found multiple times in multiple places, but whether it can overtake existing variants is unclear. To do so, BA.2.86 needs to escape antibodies while also preserving its inherent transmissibility. Otherwise, Bloom said, cases might crop up here and there, but the variant never really takes off. In other words, the BA.2.86 situation basically stays where it is right now.

    The next few weeks will reveal which of these futures we’re living in. If the number of BA.2.86 cases starts to go up, in a way that requires more attention, we’ll know soon. But each week that the variant’s spread does not jump dramatically, the less likely BA.2.86 is to end up a variant of actual concern.

    Sarah Zhang

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  • Tip Sheet: Understanding cancer-related pain, newborn screening for deadly immune disorder — and new Fred Hutch leadership

    Tip Sheet: Understanding cancer-related pain, newborn screening for deadly immune disorder — and new Fred Hutch leadership

    Newswise — SEATTLE — July 6, 2023 — Below are summaries of recent Fred Hutchinson Cancer Center research findings and other news.

    If you’re looking for resources who can comment on skin cancer awareness and skin protection during the summer months, see our list of experts and reach out to [email protected] to set up interviews.

    Cancer research and care

    Pinpointing pain: Is it cancer or cancer treatment? Distinguishing side effects of cancer treatment from potential metastatic recurrence can be difficult. In a Q&A, Dr. Hanna Hunter, medical director of cancer rehabilitation at Fred Hutch, s best practices on how doctors and patients can work together to manage pain symptoms.     

    American Society of Clinical Oncology Annual Meeting 2023 highlights: Fine-tuning cancer care Fred Hutch researchers at ASCO’s annual meeting d their latest findings in cellular immunotherapy, early detection cancer screening tests, interplays between the microbiome and genetics in colorectal cancer and more.    

    Cancer Health Equity Podcast: Nurses in cancer care The latest episode of Fred Hutch’s Office of Community Outreach and Engagement’s monthly podcast explores the role of nurses in cancer care and how they’re part of working toward health and well-being for everyone. Two Fred Hutch nurses on the blood and bone marrow transplant team — Arlyce Coumar and Jennifer Lynch — their stories of working with patients and families, as well as educating other nurses. They also discussed how nurses are getting more engaged in advocating for policies in health care. Fred Hutch community health educators Aden Afework, who works with African-American populations, and Snowy Johnson, who works with Indigenous populations, moderated the discussion.

    Severe combined immunodeficiency A new analysis published in The Lancet shows that newborn screening is the biggest factor in preventing deaths from the rare inherited disorder called severe combined immunodeficiency, also known as “bubble boy disease.” Babies born with SCID appear healthy at birth but are vulnerable to infections and usually die within the first two years of life unless they’re treated with immune-restoring treatment, such as stem cell transplant. Dr. Monica Thakar, pediatric bone marrow transplant physician, led the analysis which was published June 20. Read more in a National Institute of Allergy and Infectious Disease news release.

    Diversity, equity and inclusion

    Me Loving You: Themes of healing and moving forward Fred Hutch celebrated the start of Pride month with its fourth art installation as part of the Public Art & Community Dialogue Program featuring artist Ariadne Campanella. Initiated by Fred Hutch’s DEI Core, the program commissions artwork from artists representing diverse communities with the aim of engaging Fred Hutch employees and the broader community in conversations of solidarity with underrepresented groups. Campanella, a queer, non-binary trans woman and mixed media artist, was selected to create a piece focusing on LGBTQIA+ communities as they reflect on healing and moving from surviving to thriving.    

    New Fred Hutch leaders

    Dr. Sara Hurvitz joins Fred Hutch, University of Washington Breast oncologist Dr. Sara Hurvitz has been named the new senior vice president of the Clinical Research Division at Fred Hutch and head of the Division of Hematology and Oncology at the University of Washington Department of Medicine. She will begin her role Aug. 1. Currently at UCLA, Hurvitz is an international expert in breast oncology and a leader in clinical and laboratory-based oncology research, with extensive experience in leading clinical trials spanning all phases.   

    Fred Hutch announces new member, leadership on board of directors Fred Hutch announced one new member of its board of directors and its newly elected chair and vice chair. Pete Shimer, chief operating officer at Deloitte, will join the board. Leigh Morgan, chief strategy and operating officer at the Nia Tero Foundation, has been appointed the new chair of the board of directors, and Sean Boyle, chief operating officer at Omniva, has been appointed vice chair.    

    Awards and grants

    Dr. Mroj Alassaf named a 2023 Helen Hay Whitney Fellow Dr. Mroj Alassaf, postdoctoral fellow in Dr. Akhila Rajan’s lab, received a 3 year $215,000 Helen Hay Whitney foundation fellowship. Her work focuses on how mitochondrial components from fat can reach the brain and what influence they have on its health. A neurobiologist by training, Alassaf joined Rajan’s team after showing in her graduate work how a new mitochondrial protein contributes to neuronal health.    

    Dr. Sita Kugel receives V Foundation Translational Research Award Pancreatic cancer researcher Dr. Sita Kugel has received an inaugural Translational Research Award from the V Foundation for Cancer Research. The $800,000, four-year grant will allow Kugel to pursue an innovative Phase 1b clinical trial to translate from the lab to the clinic breakthroughs her group has made in developing a tailored treatment for a subtype of pancreatic cancer.    

    Dr. Cecilia Moens elected inaugural member of the Society for Developmental Biology Academy Developmental biologist Dr. Cecilia Moens joins nine other scientists elected to the newly created Society for Developmental Biology Academy. Moens work focuses on using zebrafish as a model to study the genes that control the brain’s early development. Her current research looks at how immature neurons make their connections to muscles and other neurons in the process of building functional circuits.    

    Lung cancer expert Dr. McGarry Houghton receives Satya and Rao Remala Family Endowed Chair Dr. McGarry Houghton, a pulmonary physician-scientist, studies the immune system’s role in cancer and lung cancer early detection. He was named the first recipient of the Satya and Rao Remala Family Endowed Chair, which provides support for a researcher working on both lung cancer and the promotion of equitable access to health and education. Houghton is pursuing a plasma-based diagnostic tool that would be used in conjunction with CT screening for lung cancer early detection.   

    Virus researchers Cohn and Blanco-Melo win coveted grants Drs. Lillian Cohn and Daniel Blanco-Melo are both early career scientists studying viruses and recently received support for their work through scholar programs. Cohn was named a biomedical scholar by the Pew Charitable Trust and Blanco-Melo was named a Searle scholar. Cohn’s research focuses on finding ways to cure HIV/AIDS by eradicating reservoirs of latently infected blood cells that persist despite continuous therapy with antiviral drugs. Blanco-Melo focuses on exploring how viruses evolve and how the human immune response to them changes over time.    

    Science spotlight Science Spotlight is a monthly installment of articles written by postdoctoral fellows at Fred Hutch that summarize new research papers from Fred Hutch scientists. If you’re interested in learning more or covering these topics, contact: [email protected]

    # # #

    Fred Hutchinson Cancer Center unites individualized care and advanced research to provide the latest cancer treatment options and accelerate 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 and has network affiliations with hospitals in four states. Fred Hutch also serves as UW Medicine’s cancer program.

    Fred Hutchinson Cancer Center

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  • Fred Hutch at AACR: New targets for cancer therapies, experts available in diversity and cancer screening tests — and Fred Hutch’s Philip Greenberg becomes AACR president

    Fred Hutch at AACR: New targets for cancer therapies, experts available in diversity and cancer screening tests — and Fred Hutch’s Philip Greenberg becomes AACR president

    Newswise — SEATTLE — April 6, 2023 — Experts from Fred Hutchinson Cancer Center will present their latest findings on targets in RIT1-driven cancers, ROR1 CAR T-cell immunotherapy, interplay of the microbiome and genetics in colorectal cancer and more at the annual meeting of the American Association for Cancer Research, to be held April 14-19 in Orlando, Florida. 

    Other meeting highlights include:

    Philip Greenberg, M.D. of Fred Hutch will become AACR president.

    Public health researcher and biostatistician Ruth Etizioni, Ph.D. will discuss new and emerging tests for early detection of cancer.

    Christopher Li, M.D., MPH, a national leader in diversity, equity and inclusion efforts at cancer centers, will best practices and strategies to enhance diversity. 

    Below are highlights of work to be presented, and you can follow Fred Hutch’s AACR updates on Twitter #AACR23.

    For media requests during AACR, please contact . 

    AACR news

    Meet and Greet: Meet the editors-in-chief of Cancer Immunology Research Monday, April 17, 2023, 9:30-10:30 a.m. 

    Meeting: Meet the 2023-2024 AACR President, Philip Greenberg Tuesday, April 18, 2023, 1:30-2:30 p.m.

    Fred Hutch’s Philip Greenberg, M.D., one of two editors-in-chief of AACR’s Cancer Immunology Research, will participate in an April 17 discussion of the scope and types of research manuscripts they’re looking to publish. Greenberg, currently president-elect of AACR, will become AACR president during the meeting and be at the April 18 “Meet the 2023-2024 AACR President” session. He leads the Program in Immunology at Fred Hutch and holds the Rona Jaffe Foundation Endowed Chair.  

    Early detection and screening

    Educational session: How can we realize the promise of novel technologies for early cancer detection? Presentation: Developing realistic expectations for new cancer screening tests Friday, April 14, 2023, 3:01-3:21 p.m. Presenter: Ruth Etzioni, Ph.D.

    Public health researcher and biostatistician Ruth Etzioni, Ph.D. will join an educational session to talk about novel cancer screening tests based on liquid biopsies, with a particular focus on multi-cancer early detection testing. She said that while there are some studies that show how well the tests detect different cancers, the extent to which this will translate into lives saved is still unclear. Etzioni, who holds the Rosalie and Harold Rea Brown Endowed Chair at Fred Hutch and received a $7.4 million National Cancer Institute grant to study cancer diagnostics, will discuss the process by which population screening leads to reduction in cancer deaths, why some past cancer screening trials have led to disappointing results and what needs to be done now to generate convincing evidence that population screening using the new tests will reduce cancer deaths. 

    Precision oncology

    Educational session: Tumor heterogeneity: Rapid autopsy to longitudinal biopsies Presentation: Intra and inter-tumor heterogeneity across cancer metastases: A reality check for targeted therapeutics and the utility of non-invasive biomarkers Saturday, April 15, 2023, 3:16-3:33 p.m. Presenter: Peter Nelson, M.D.

    In a session on the use of rapid autopsies to understand cancer metastasis, Peter Nelson, M.D. will discuss the impact of tumor heterogeneity on treatment resistance. Nelson, who is a prostate cancer expert and is the vice president of Precision Oncology at Fred Hutch, will also explain how studies of metastatic tumors improve our understanding of molecular imaging such as PET scans as well as minimally-invasive diagnostic methods including circulating tumor DNA. Nelson directs the Stuart and Molly Sloan Precision Oncology Institute at Fred Hutch and holds an endowed chair with the same name.  

    Session: Small cell lung cancer: Moving biology to the clinic Presentation: Measuring and modulating SCLC transcriptional heterogeneity from murine models to clinical trials Monday, April 17, 2023, 1:00-1:20 p.m. Presenter: Joseph Hiatt, M.D., Ph.D. (On Twitter and LinkedIn)

    Physician-scientist Joseph Hiatt, M.D., Ph.D. will give an update on Fred Hutch preclinical research that has identified a molecular pathway that could make more cases of small cell lung cancer responsive to checkpoint inhibition. The approach is now being studied in a clinical trial. Hiatt, who is a research fellow in the MacPherson lab at Fred Hutch, will also present a new liquid biopsy method to predict subtypes of small cell lung cancer using cell-free DNA. This could be used to link patients’ subtypes to their treatment outcomes to help personalize clinical trial enrollment. The work is part of the Fred Hutch Lung Specialized Project of Research Excellence (SPORE), a five-year $13 million grant from the National Cancer Institute to expedite lung cancer research from the lab to the clinic. 

    Session: Ras-related signaling Poster: Protein-level regulation of wild-type and mutant RIT1 by the deubiquitinase USP9X Monday, April 17, 2023, 1:30-5 p.m. Presenter: Amanda Riley (On LinkedIn)

    Mutations in the gene RIT1 account for about 13,500 cases of non-small cell lung cancer diagnoses each year, with limited treatment options. Graduate student Amanda Riley, working in the Fred Hutch lab of Alice Berger, Ph.D., will give an update on their work to find targeted therapies for RIT1-driven cancers. They’ve identified a regulator of RIT1, a protein called USP9X. Using mouse models and existing inhibitors of USP9X, the researchers are evaluating this potential drug target. The project is part of Berger’s 7-year NIH MERIT award to pursue targeted therapies for mutations in lung cancer. Berger holds the Innovators Network Endowed Chair at Fred Hutch, follow her on Twitter. 

    Cancer biology

    Major symposium: Targeting RNA splicing in cancer and the immune system Presentation: From splicing to polyadenylation in tumor immunity Sunday, April 16, 2023, 1:55-2:15 p.m. Presenter: Robert Bradley, Ph.D. (On Twitter)

    Computational biologist and biophysicist Robert Bradley, Ph.D. will present new work on a biological process that’s growing in attention for its role in controlling cancer growth. Alternative polyadenylation is part of making mRNA and it’s disrupted in many cancers, though it’s not clear how the dysregulation contributes to tumors. Bradley, who holds the McIlwain Family Endowed Chair in Data Science at Fred Hutch, will discuss a CRISPR-Cas9-based screen to test the functional importance of alternative polyadenylation to tumor growth. 

    Cellular immunotherapy

    Minisymposium: Genetically engineered anticancer T cells Presentation: NKTR-255, a polymer-conjugated IL-15, dramatically improves ROR1 CAR-T cell persistence and anti-tumor efficacy in an autochthonous model of ROR1+ lung cancer Sunday, April 16, 2023, 4:10-4:25 p.m. Presenter: Sam Nutt

    Using a mouse model of lung cancer that closely resembles human disease, graduate student Sam Nutt in the Fred Hutch lab of Shivani Srivastava, Ph.D. (on Twitter) will present a study on whether NKTR-255, a drug that stimulates the immune system to fight cancer, can improve the anticancer effects of chimeric antigen receptor (CAR) T cells. The Fred Hutch team is using a CAR-T cell targeting the tumor antigen ROR1, which is a marker on many breast and lung cancer patients. Their findings suggest that NKTR-255 treatment improves the persistence and function of ROR1 CAR T cells, and that these two therapies work together to boost immune function in the tumor microenvironment, resulting in significantly improved tumor control. The team is continuing to evaluate the combined approach for treatment of solid tumors. Read more about the lab’s work to develop cellular therapies for solid tumors.

    Colorectal cancer risk and prevention

    Session: Biological and behavioral factors in cancer surveillance, prevention and survivorship Poster: Evaluation of intra-tumoral pks+ E. coli, enterotoxigenic B. fragilis and Fusobacterium nucleatum and in early onset disease, in colorectal cancer cases Monday, April 17, 2023, 1:30-5:00 p.m. Presenter: Meredith Hullar, Ph.D. 

    Meredith Hullar, Ph.D., a principal staff scientist at Fred Hutch, studies the gut microbiome and its interplay with diet and cancer risk. She will present a new study that revealed different patterns of microbes in colorectal cancer tumors that are present in patients with early onset colorectal cancer, which has increased in incidence in people who are 50 years old and younger. Since some microbes can help tumors grow, understanding the microbiome may help predict which colorectal cancer patients will have increased odds of lower survival and may support targeted intervention strategies to improve survivorship. Learn more about her work in a Fred Hutch news story.

    Session: Aging, immune factors and metabolomics Poster: Association between HLA-KIR allele interaction combinations and density of T-cell subsets in colorectal cancer Monday, April 17, 2023, 1:30-5:00 p.m. Presenter: Claire E. Thomas, Ph.D., MPH (On Twitter)

    Session: Diet, alcohol, tobacco use, and other lifestyle factors Poster: Lifestyle and environmental factors in relation to colorectal cancer risk and survival by colibactin tumor mutational signature status Wednesday, April 19, 2023, 9:00 a.m.-12:30 p.m. Presenter: Claire E. Thomas, Ph.D., MPH (On Twitter)

    Claire E. Thomas, Ph.D., MPH, a post-doctoral researcher at Fred Hutch, will present two posters looking at genetic and molecular risks underlying colorectal cancer. In the first poster, she examines whether immune function gene combinations are related to T-cell density within colorectal cancer tumors. The findings could help determine how an individual’s genetic background is related to T-cells and immune response to fight cancer. 

    In a second poster, Thomas will present a study examining whether lifestyle and environmental factors are differentially associated with colorectal cancer risk and survival for cases with and without the mutational signature SBS88. SBS88 is present in some colorectal cancer tumors and is related to production of the genotoxin colbactin from exposure to some strains of Escherichia coli. The findings show that among cases with the SBS88 signature, higher BMI category was associated with worse colorectal cancer outcomes. 

    Thomas works with Fred Hutch’s Ulrike Peters, Ph.D., MPH, who is a molecular and genetic epidemiologist and holds the Fred Hutch 40th Anniversary Endowed Chair, and with Amanda Phipps, Ph.D., MPH, an epidemiologist. The research team aims to understand underlying genetic risks in cancer and how to intervene. A recent Nature Genetics study from the Peters team identified 100 new genetic risk variants in colorectal cancer.

    Diversity, equity and inclusion

    Meet-the-expert session: Plan to enhance diversity: Opportunities, challenges, best practices and innovative strategies to advance a culture of inclusive excellence at cancer centers Tuesday, April 18, 2023, 7:00-7:45 a.m. Presenter: Christopher Li, M.D., Ph.D. (On LinkedIn)

    Christopher Li, M.D., Ph.D., vice president of Faculty Affairs and Diversity at Fred Hutch, is a nationally recognized leader in efforts to ensure that cancer research benefits all people. At AACR, he will insights from his efforts to help build and maintain a diverse, equitable and inclusive workforce at Fred Hutch and to collaborate with leaders at other cancer centers. Li, who holds the Helen G. Edson Endowed Chair for Breast Cancer Research, is also an epidemiologist who studies breast cancer risk factors, breast cancer recurrence and cancer health disparities.

    Clinical trials

    Major symposium: Sex hormones and cancer Presentation: Sex differences in severe adverse events in patients receiving immunotherapy, targeted therapy, or chemotherapy in Cancer clinical trials: An evidentiary perspective Tuesday, April 18, 2023, 1:25-1:45 p.m. Presenter: Joseph Unger, Ph.D. (On Twitter)

    Biostatistician and health services researcher Joseph Unger, Ph.D. will insights based on findings he published in Journal of Clinical Oncology in how women experience greater adverse effects from cancer treatment, whether it’s chemotherapy, targeted therapy or immunotherapy. The data came from more than 23,000 people participating in 202 clinical trials as part of the SWOG Cancer Research Network, which described the study in a blog post. Unger uses big data to understand treatment outcomes and disparities in cancer, with the aim of revealing problems in cancer care that then allow for ways to predict and prevent the issues before they impede patients.  

    Late-breaking poster session: Clinical research 3 Poster: Biomarker analysis from AMPECT correlating response to nab-sirolimus with TSC1 and TSC2 inactivating alterations Wednesday, April 19, 9 a.m.-12:30 p.m. Presenter: Lee Cranmer, M.D., Ph.D.

    Lee Cranmer, M.D., Ph.D. leads the Bob and Eileen Gilman Family Sarcoma Research Program at Fred Hutch. A recent Fred Hutch news story featured a patient Cranmer treated for a type of cartilage cancer, called chondrosarcoma.

    Note: Fred Hutch and its scientists who contributed to these discoveries may stand to benefit from their commercialization. See links above to AACR 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.

    # # #

    Fred Hutchinson Cancer Center unites individualized care and advanced research to provide the latest cancer treatment options and accelerate 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 and has network affiliations with hospitals in four states. Fred Hutch also serves as UW Medicine’s cancer program.

    Fred Hutchinson Cancer Center

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  • Fred Hutch at ASH: Global insights on AML outcomes, COVID-19 and cancer, CD19 CAR T-cell therapy updates, latest on precision oncology — and more

    Fred Hutch at ASH: Global insights on AML outcomes, COVID-19 and cancer, CD19 CAR T-cell therapy updates, latest on precision oncology — and more

    Newswise — SEATTLE — Dec. 1, 2022 — The 64th Annual Meeting and Exposition of the American Society of Hematology (ASH) will take place virtually and in person Dec. 10-13 in New Orleans, Louisiana.

    Below are highlights of Fred Hutchinson Cancer Center research to be presented, and you can follow Fred Hutch updates on Twitter #ASH22. You can also check out Fred Hutch’s booth 2622 in the exhibit hall.

    This year’s ASH press program highlights work below by Fred Hutch:

    Poster presentation: An analysis of the worldwide utilization of hematopoietic stem cell transplantation for acute myeloid leukemia Abstract: 3638 Presenter: Molly Tokaz Other Fred Hutch authors: Andrew Cowan and Mary-Beth Percival Sunday, Dec. 11, 6 p.m.

    A global study of use of transplantation for acute myeloid leukemia led by Fred Hutch fellow Dr. Molly Tokaz will be featured in a Dec. 7 virtual-only ASH briefing, “Building Solutions to Challenges in Health Equity.”

    Late-breaking session: Zanubrutinib demonstrates superior progression-free survival (PFS) compared with ibrutinib for treatment of relapsed/refractory chronic lymphocytic leukemia and small lymphocytic lymphoma (R/R CLL/SLL): Results from final analysis of ALPINE randomized phase 3 study Abstract: LBA-6 Senior author: Mazyar Shadman (On Twitter: @mshadman) Tuesday, Dec. 13, 8:30 a.m.

    A Dec. 12 media briefing on late-breaking abstracts will include an abstract co-authored by Fred Hutch’s Dr. Mazyar Shadman, a chronic lymphocytic leukemia and lymphoma physician-investigator. The abstract gives an update on a clinical trial assessing a next-generation Bruton tyrosine kinase inhibitor.

    Also on the press program, Dr. Stephanie Lee, former president of ASH, will moderate the Dec. 10 briefing “New Drugs, New Targets.” Dr. Lee is a transplant physician-scientist and expert in chronic graft-vs.-host-disease and holds the David and Patricia Giuliani/Oliver Press Endowed Chair in Cancer Research at Fred Hutch.

    Learn more in the ASH Annual Meeting press program.

    Poster presentation: Timing of PD-L1 Blockade with Durvalumab May Affect Outcomes of CD19 CAR-T Cell Therapy for Relapsed/Refractory Large B-Cell Lymphoma Abstract: 3316 Presenter: Alexandre Hirayama (On Twitter: @xanira) Sunday, Dec. 11, 6 p.m.

    Adding checkpoint blockades may make CAR T-cell therapy more effective against blood cancers, but combination trial results so far have been disappointing. This clinical trial evaluates the importance of timing of the therapies.

    Poster presentation: CAR T-cell therapy for relapsed or refractory large B-cell lymphoma using a fully human CD10-targeted single chain variable fragment: Results of a first-in-human phase I/II study Abstract: 4654 Presenter: Nicolas Gazeau (On Twitter: @NGazeau14) Monday, Dec. 12, 6 p.m.

    CAR T-cell therapies targeting the marker CD19 on cancer cells achieve high response rates in patients with relapsed or refractory large B-cell lymphoma, but durable responses are only achieved in 30-40% of patients. Based on clinical evidence showing lack of a durable response linked to a mouse-based component of the engineered cell, a phase I/II clinical trial is evaluating the effectiveness of the CAR T rebuilt with a human-based component instead. 

    Poster presentation: 3-Year follow-up analysis of ZUMA-5: a Phase 2 study of axicabtagene ciloleucel (Axi-Cel) in patients with relapsed/refractory (R/R) indolent non-hodgkin lymphoma (iNHL)

    Abstract: 4660 Co-author: David Maloney Monday Dec. 12, 6 p.m.

    This is a 3-year follow-up of the ZUMA-5 study, which shows that the CAR T-cell therapy called axi-cel demonstrated continued durable responses in patients with relapsed/refractory indolent non-hodgkin’s lymphoma (R/R iNHL) with improved survival observed in patients with marginal zone lymphoma. Late progression or death due to lymphoma or study treatment were uncommon and no new safety signals arose since the 2-year analysis. The research team also looked at biomarkers related to outcomes and found that preinfusion immunosuppressive Treg-related biomarkers were associated with relapse in patients with follicular lymphoma.

    Poster presentation: Circulating tumor DNA in untreated classical hodgkin lymphoma patients treated with pembrolizumab and chemotherapy: Dynamic response assessment and correlation with baseline metabolic tumor volume

    Abstract: 2913 Presenter: Ryan Lynch Sunday, Dec. 11, 6 p.m.

    This abstract presents updated results of a Fred Hutch single-center investigator-initiated clinical trial of the checkpoint inhibitor called pembrolizumab plus a chemotherapy for untreated classical Hodgkin lymphoma. The researchers continued to demonstrate a favorable safety profile with excellent efficacy (median follow up of 2.1 years, 2-year progression free survival of 97%). They also present new correlative data with circulating tumor DNA (ctDNA) for detection of minimal residual disease. It is possible that immunotherapy combinations may be associated with increased rates of uptake of residual F-fluorodeoxyglucose, which is a nonspecific imaging agent, and the team found that many of these patients have not had their cancer come back even several years later. In contrast, ctDNA was able to identify the lack of ctDNA clearance in the only patient who has relapsed today despite favorable initial PET scans. These findings indicate that ctDNA may represent a more sensitive and specific response assessment tool to be studied in larger datasets.

    Oral presentation: Self-reported experiences of adult hematopoietic cell transplantation survivors with COVID-19 vaccination and infection Abstract: 378 Presenter: Emily Liang (On Twitter: @emilyliangmd) Saturday, Dec. 10, 5:15 p.m.

    In a report of about 1700 stem cell transplant survivors, Fred Hutch clinicians found that vaccinated patients and their household contacts had a lower rate of COVID-19 infection compared with unvaccinated individuals (patients: 6% vs 68%, or 10-fold lower rate of infection; household contacts: 10% vs 46%, or 4-fold lower rate of infection) and were more likely to take additional safety precautions including masking and social distancing. The Fred Hutch team hopes the findings encourage others to receive the COVID-19 vaccination given the protective effect of vaccination and low rates of vaccine-related side effects.

    Poster presentation: A risk model for CML patients with COVID-19: Importance of molecular response in the context of age, comorbidities and country income Abstract: 4327 Presenter: Jerry Radich Monday, Dec. 12, 6 p.m.

    Researchers on the iCMLf CANDID study, a collaboration of 157 centers from 58 countries and with nearly 700 chronic myeloid leukemia patients participating, are looking for risk factors to predict which people with chronic myeloid leukemia are more likely to suffer worse outcomes from COVID-19. Dr. Jerry Radich, who holds the Kurt Enslein Endowed Chair at Fred Hutch, will report on the group’s findings, which show that age, molecular aspects of an individual’s CML, comorbidities and wealth of countries impact COVID-19 outcomes in CML patients.

    Oral presentation: Anti-leukemic activity of STRO-002 a novel folate receptor-α (FR-α)-targeting ADC in relapsed/refractory CBF2AT3-GLIS2 AML Abstract: 66 Presenter: Soheil Meshinchi Saturday, Dec. 10, 10:45 a..m.

    Acute myeloid leukemia remains one of the most difficult to treat pediatric cancers. Physician-scientist Dr. Soheil Meshinchi has led efforts to characterize the biology of this cancer in young patients and to identify targeted treatments that best suit their specific disease. At ASH, he will give an update on one such treatment, which was tested as part of Project Stella at Fred Hutch. His hope is that with detailed molecular testing of each patient followed by a targeted therapy, that children with the disease will go on to live long and healthy lives.

    Poster presentation: Umbrella trial in myeloid malignancies: The myeloMATCH national clinical trials network precision medicine initiative Abstract: 4080 Co-author: Jerry Radich Monday, Dec. 12, 6 p.m.

    Fred Hutch is part of an initiative led by the National Cancer Institute to help people newly diagnosed with acute myeloid leukemia and myelodysplastic syndromes to have a rapid (less than 3 days) testing of the clinical and molecular makeup of their disease and then be matched with treatment trials with promising therapeutic combinations. Fred Hutch, under the leadership of Dr. Jerry Radich, has been chosen to coordinate and perform the diagnostic and monitoring aspects of this nationwide initiative.

    Oral session: Allogeneic transplantation: Acute and chronic GVHD, immune reconstitution: Clinical studies exploring the immunobiology of HCT Abstract: 722 Moderator: Kate Markey (On Twitter: @katemarkey) Saturday, Dec. 10, 9:30 a.m.

    New insights – bolstered by emerging technological breakthroughs – on how the immune system recovers following transplantation are increasing our understanding of post-transplant complications like graft-versus-host disease. Fred Hutch’s Dr. Kate Markey, a physician-scientist and expert on how the microbiome affects recovery from transplantation, will moderate this session that includes clinical data from groups exploring T cell recovery after transplantation and clinical reports.

    Poster presentation: HSCs engraft in a stochastic pattern and form clonal pools following transplantation Abstract: 2527 Presenter: Stefan Radtke Sunday, Dec. 11, 6 p.m.

    Previous Fred Hutch studies discovered a subtype of hematopoietic stem cells that give rise to all other cells in the blood and immune systems, which could be a powerful therapeutic target. But because the cells are so rare, they’ve been difficult to study. Findings in this poster used a new type of bar coding to track individual cells and reveal some of the cellular dynamics that underlie their regenerative abilities.

    Poster presentation: Clinical and functional implications of MYC variants as a new class of pathogenic variants in AML Abstract: 1472 Presenter: Danielle Kirkey Saturday, Dec. 10, 5:30 p.m.

    Understanding the underlying genetics of pediatric acute myeloid leukemia can help determine how best to treat this difficult to treat disease. One of the genetic players is MYC, an oncogene involved in a majority of human cancers. In this work, Fred Hutch researchers defined the presence of different MYC variants and found that some occur in about 3.5% of pediatric patients with AML. The team did additional analyses to link MYC variants with other previously known high-risk features of AML and found those associations to be linked to clinical outcomes, which will allow for more nuanced stratification of a patient’s risk and will help determine optimal treatment regimens.

    Oral presentation: Treatment patterns and outcomes of patients with primary or secondary acute myeloid leukemia by type of site (academic or community government): A CONNECT® Myeloid Registry Study

    Abstract: 4023 Presenter: Bart Scott Monday, Dec 12, 6 p.m.

    This research was conducted to better understand management of secondary acute myeloid leukemias (SAML), which is a type of blood cancer that starts in white blood cells that grow in the bone marrow, often affecting people who have one of these blood cell diseases: myelodysplastic syndrome (MDS), myeloproliferative disorder (MPD) and aplastic anemia. The Fred Hutch team evaluated treatment patterns and outcomes in patients enrolled in the CONNECT® Myeloid Disease Registry. The findings indicate that outcomes for patients with AML in the registry are consistent with previously reported outcomes. This analysis suggests that contrary to commonly held perceptions, site of care does not affect overall patient outcomes. The clinically meaningful increase in overall survival in patients receiving an allogeneic hematopoietic stem cell transplant, regardless of primary or secondary AML further emphasizes the importance of providing patients with the opportunity for transplant.

    Poster presentation: Clinical outcome and treatment-related mortality in patients with acute myeloid leukemia treated at the Uganda Cancer Institute

    Abstract: 4031 Presenter: Clement Dove Okello Co-author: Soheil Meshinchi Monday, Dec 12, 6 p.m.

    A retrospective review of acute myeloid leukemia outcomes at the Uganda Cancer Institute examined factors associated with treatment-related mortality. Treatment of AML is similar across countries, but treatment-related mortality is significantly greater in low-income countries compared with high-income countries. This study by UCI and Fred Hutch researchers examined factors that could be contributing to greater mortality, in hopes of improving outcomes. Through the UCI-Fred Hutch Collaboration, Dr. Soheil Meshinchi, a Fred Hutch expert in AML, advised on the project.

    Poster presentation: Revised prognostic index for patients with acute myeloid leukemia and other high-grade myeloid neoplasms in first relapse

    Abstract: 1385 Presenter: Noam E. Kopmar Saturday, Dec 10, 5:30 p.m.

    Though many patients with acute myeloid leukemia will achieve a first complete remission, most patients will relapse. Fred Hutch researchers looked at predictors of relapse and examined methods to create an improved risk stratification model that will better predict likelihood of a second complete remission and overall survival after relapse. Through a better understanding of prognosis, providers may improve their ability to determine the optimal treatment approach and also better inform the counseling provided to patients regarding prognosis.

    Poster presentation: Prognostic significance of chromosomal genomic array testing in adults with newly diagnosed acute lymphoblastic leukemia

    Abstract: 4145 Presenter: Noam E. Kopmar Saturday, Dec 12, 6 p.m.

    This project led by members of the acute leukemia and myeloid malignancies research group at Fred Hutch is aimed at improving prognostic capabilities at the time of either a new diagnosis or at the time of first relapse, correlating chromosomal genomic array testing results with key demographic and outcomes data. Having a better understanding of prognosis may improve the ability of providers to determine the optimal treatment approach and also better inform the counseling that is provided to patients regarding prognosis.

    The disease-killing T cells of the immune system develop their capabilities in a small, butterfly-shaped gland in the chest called the thymus. The thymus can regenerate to keep its immune function strong, but it wears out from stress, infection and aging. At ASH, Fred Hutch researchers will report their latest findings on how to repair the thymus:

    Oral presentation: Interleukin-18 suppresses regeneration of the thymus

    Abstract: 483 Presenter: David Granadier Co-author Jarrod Dudakov (On Twitter: @Dudakov_Lab) Monday, Dec 12, 4:30 p.m.

    Research by graduate student David Granadier in Dr. Jarrod Dudakov’s lab implicates the cytokine IL-18 in regulating the ability of the thymus to repair itself. This presentation will these latest insights. More on the signaling pathways involved in thymic regeneration and their implications for therapeutics in a Fred Hutch news story.

    Poster presentation: The zinc-sensing receptor GPR39 is a master regulator of immune reconstitution after bone marrow transplant in the thymus and in the bone marrow

    Abstract: 4581 Presenter: Lorenzo Iovino Co-author Jarrod Dudakov (On Twitter: @Dudakov_Lab) Monday, Dec 12, 6 p.m.

    Zinc is well-known for its immune-boosting properties, and recently Dr. Lorenzo Iovino in Dudakov’s lab at Fred Hutch revealed how zinc supports immune function through the thymus. Iovino will give an update on the work and how it could be used to improve treatments for cancer patients.

    Note: Fred Hutch and the scientists who contributed to these 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 report about the safety, efficacy, or likelihood of regulatory approval of these investigational products and/or therapies.

    # # #

    Fred Hutchinson Cancer Center unites comprehensive care and advanced research to provide the latest cancer treatment options and accelerate discoveries that prevent, treat and defeat 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, HIV/AIDS prevention, immunotherapy and COVID-19 vaccines. Fred Hutch operates eight clinical care sites that provide medical oncology, infusion, radiation, proton therapy and related services and has network affiliations with hospitals in four states. Fred Hutch also serves as UW Medicine’s cancer program.

    Please note that our organization was renamed Fred Hutchinson Cancer Center in April 2022, following the merger of long-time partners, Fred Hutchinson Cancer Research Center and Seattle Cancer Care Alliance. 

    Fred Hutchinson Cancer Center

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  • The ‘End’ of COVID Is Still Far Worse Than We Imagined

    The ‘End’ of COVID Is Still Far Worse Than We Imagined

    When is the pandemic “over”? In the early days of 2020, we envisioned it ending with the novel coronavirus going away entirely. When this became impossible, we hoped instead for elimination: If enough people got vaccinated, herd immunity might largely stop the virus from spreading. When this too became impossible, we accepted that the virus would still circulate but imagined that it could become, optimistically, like one of the four coronaviruses that cause common colds or, pessimistically, like something more severe, akin to the flu.

    Instead, COVID has settled into something far worse than the flu. When President Joe Biden declared this week, “The pandemic is over. If you notice, no one’s wearing masks,” the country was still recording more than 400 COVID deaths a day—more than triple the average number from flu.

    This shifting of goal posts is, in part, a reckoning with the biological reality of COVID. The virus that came out of Wuhan, China, in 2019 was already so good at spreading—including from people without symptoms—that eradication probably never stood a chance once COVID took off internationally. “I don’t think that was ever really practically possible,” says Stephen Morse, an epidemiologist at Columbia. In time, it also became clear that immunity to COVID is simply not durable enough for elimination through herd immunity. The virus evolves too rapidly, and our own immunity to COVID infection fades too quickly—as it does with other respiratory viruses—even as immunity against severe disease tends to persist. (The elderly who mount weaker immune responses remain the most vulnerable: 88 percent of COVID deaths so far in September have been in people over 65.) With a public weary of pandemic measures and a government reluctant to push them, the situation seems unlikely to improve anytime soon. Trevor Bedford, a virologist at the Fred Hutchinson Cancer Center, estimates that COVID will continue to exact a death toll of 100,000 Americans a year in the near future. This too is approximately three times that of a typical flu year.

    I keep returning to the flu because, back in early 2021, with vaccine excitement still fresh in the air, several experts told my colleague Alexis Madrigal that a reasonable threshold for lifting COVID restrictions was 100 deaths a day, roughly on par with flu. We largely tolerate, the thinking went, the risk of flu without major disruptions to our lives. Since then, widespread immunity, better treatments, and the less virulent Omicron variant have together pushed the risk of COVID to individuals down to a flu-like level. But across the whole population, COVID is still killing many times more people than influenza is, because it is still sickening so many more people.

    Bedford told me he estimates that Omicron has infected 80 percent of Americans. Going forward, COVID might continue to infect 50 percent of the population every year, even without another Omicron-like leap in evolution. In contrast, flu sickens an estimated 10 to 20 percent of Americans a year. These are estimates, because lack of testing hampers accurate case counts for both diseases, but COVID’s higher death toll is a function of higher transmission. The tens of thousands of recorded cases—likely hundreds of thousands of actual cases every day—also add to the burden of long COVID.

    The challenge of driving down COVID transmission has also become clearer with time. In early 2021, the initially spectacular vaccine-efficacy data bolstered optimism that vaccination could significantly dampen transmission. Breakthrough cases were downplayed as very rare. And they were—at first. But immunity to infection is not durable against common respiratory viruses. Flu, the four common-cold coronaviruses, respiratory syncytial virus (RSV), and others all reinfect us over and over again. The same proved true with COVID. “Right at the beginning, we should have made that very clear. When you saw 95 percent against mild disease, with the trials done in December 2020, we should have said right then this is not going to last,” says Paul Offit, the director of the Vaccine Education Center at Children’s Hospital of Philadelphia. Even vaccinating the whole world would not eliminate COVID transmission.

    This coronavirus has also proved a wilier opponent than expected. Despite a relatively slow rate of mutation at the beginning of the pandemic, it soon evolved into variants that are more inherently contagious and better at evading immunity. With each major wave, “the virus has only gotten more transmissible,” says Ruth Karron, a vaccine researcher at Johns Hopkins. The coronavirus cannot keep becoming more transmissible forever, but it can keep changing to evade our immunity essentially forever. Its rate of evolution is much higher than that of other common-cold coronaviruses. It’s higher than that of even H3N2 flu—the most troublesome and fastest-evolving of the influenza viruses. Omicron, according to Bedford, is the equivalent of five years of H3N2 evolution, and its subvariants are still outpacing H3N2’s usual rate. We don’t know how often Omicron-like events will happen. COVID’s rate of change may eventually slow down when the virus is no longer novel in humans, or it may surprise us again.

    In the past, flu pandemics “ended” after the virus swept through so much of the population that it could no longer cause huge waves. But the pandemic virus did not disappear; it became the new seasonal-flu virus. The 1968 H3N2 pandemic, for example, seeded the H3N2 flu that still sickens people today. “I suspect it’s probably caused even more morbidity and mortality in all those years since 1968,” Morse says. The pandemic ended, but the virus continued killing people.

    Ironically, H3N2 did go away during the coronavirus pandemic. Measures such as social distancing and masking managed to almost entirely eliminate the flu. (It has not disappeared entirely, though, and may be back in full force this winter.) Cases of other respiratory viruses, such as RSV, also plummeted. Experts hoped that this would show Americans a new normal, where we don’t simply tolerate the flu and other respiratory illnesses every winter. Instead, the country is moving toward a new normal where COVID is also something we tolerate every year.

    In the same breath that President Biden said, “The pandemic is over,” he went on to say, “We still have a problem with COVID. We’re still doing a lot of work on it.” You might see this as a contradiction, or you might see it as how we deal with every other disease—an attempt at normalizing COVID, if you will. The government doesn’t treat flu, cancer, heart disease, tuberculosis, hepatitis C, etc., as national emergencies that disrupt everyday life, even as the work continues on preventing and treating them. The U.S.’s COVID strategy certainly seems to be going in that direction. Broad restrictions such as mask mandates are out of the question. Interventions targeted at those most vulnerable to severe disease exist, but they aren’t getting much fanfare. This fall’s COVID-booster campaign has been muted. Treatments such as bebtelovimab and Evusheld remain on shelves, underpublicized and underused.

    At the same time, hundreds of Americans are still dying of COVID every day and will likely continue to die of COVID every day. A cumulative annual toll of 100,000 deaths a year would still make COVID a top-10 cause of death, ahead of any other infectious disease. When the first 100,000 Americans died of COVID, in spring 2020, newspapers memorialized the grim milestone. The New York Times devoted its entire front page to chronicling the lives lost to COVID. It might have been hard to imagine, back in 2020, that the U.S. would come to accept 100,000 people dying of COVID every year. Whether or not that means the pandemic is over, the second part of the president’s statement is harder to argue with: COVID is and will remain a problem.

    Sarah Zhang

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