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

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.

For media requests during ASH, please contact Heather Platisha: [email protected].

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.