Wilmot Highlights Blood Cancer Research at National Meeting

The strength of blood cancer research at Wilmot Cancer Institute was on display recently at the American Society of Hematology (ASH) annual meeting, the premier event in this field with more than 30,000 attendees.

Wilmot physician-scientists and trainees gave six oral presentations, six talks at education sessions and workshops, showcased 15 poster abstracts, and participated in approximately 60 other projects in which University of Rochester cancer investigators were co-authors and collaborators on research led by other institutions.

“Our work this year was really an impressive demonstration of our breadth,” said Wilmot Director Jonathan Friedberg, MD, MMSc. “From basic science all the way to population science, the impact is quite high. Congratulations are in order for everyone who was involved in a project at ASH.”

Carol Fries, MD, presenting at ASH

The scope of Wilmot expertise was also wide-ranging, from those who study the mechanisms behind red blood cell production, to bone marrow failure, stem cell remodeling, leukemia and lymphoma treatment advances, and how doctors and patients can work together to arrive at the best possible treatment decisions. Many of the presenters are members of Wilmot’s three research programs: Cancer Microenvironment (CM); Genetic, Epigenetic, and Metabolism (GEM); and Cancer Prevention and Control (CPC); and the Department of Medicine at URochester.

Following is a list of presenters and co-authors:

Oral Presentations

• Carla Casulo: Clinical prognostication in the SWOG 1826 randomized clinical trial of nivolumab-AVD versus brentuximab-AVD: Performance of the advanced-stage Hodgkin lymphoma international prognostic index (A-HIPI)
• Carol Fries: Immunoglobulin variable gene diversity reflects distinct metabolic/signaling states and impacts measurable residual disease monitoring and clinical outcome in B cell acute lymphoblastic leukemia
• Kah Poh (Melissa) Loh: A decisional intervention for older patients with Acute Myeloid Leukemia and their oncologist: A pilot randomized controlled trial (RCT)
• Preeti Maurya: Neonatal platelets induce monocytes to a myeloid derived suppressor cell phenotype
• Nabil Rahman: HEXIM1 is a critical regulator of cell cycle progression and terminal maturation during steady-state and stress erythropoiesis
• Marlies Rossmann: An essential link between pyrimidine synthesis and ferroptosis suppression in erythroid differentiation

Special Talks

• Jeevisha Bajaj: Metabolic Vulnerabilities of Leukemic Stem Cells, Scientific Workshop
• Jeevisha Bajaj: Panel Discussion/Q&A
• Jane Liesveld: Rapamycin and the Rewiring of Aging, Scientific Workshop
• Kah Poh (Melissa) Loh: Treatment Options for Older Adults with AML: Recommendations on Low-Dose Cytarabine, Azacitidine, and Decitabine Regimens as Monotherapy or Combinations, Special Interest Session
• Kristen O’Dwyer: Immune Targeting in Ph Negative and Ph Positive B-ALL: Improving Outcomes and Minimizing Chemotherapy in Adult B-ALL, Education Program
• Shu-Chi Yeh: Local Bone Remodeling Shapes Hematopoietic Stem Cell (HSC)- Macrophage Interactions and Compartmentalized HSC Expansion under Inflammatory Stress, Scientific Workshop

Poster Presentations

Graduate students Michael Malloy and Nabil Rahman, who also won an abstract award at ASH

• Paul Barr: R-mini-CHOP preserves efficacy and limits toxicity for patients ≥ 80 years old with DLBCL
• Charles Chu: Initial treatment of chronic lymphocytic leukemia with low-dose high-frequency rituximab followed by addition of acalabrutinib
• Jessica Cohen: "I feel like I'm being recognized as being a part of his treatment": Caregiver perspectives of the serious illness care program for older patients with hematologic malignancies
• Wimeth Dissanayake: Identification of stage-specific regulators for neutrophil granule biogenesis
• Edgardo Franco: IDH2 mutant hematopoietic stem and progenitor cells promote endothelial niche remodeling
• Eric Huselton: A randomized Phase II trial of ASTX727 and venetoclax with or without enasidenib for newly diagnosed older adults with IDH2 mutant Acute Myeloid Leukemia: A myelomatch substudy (MM1OA-S03)
• Christina Kaszuba: Apolipoproteins from the microenvironment promote aggressive myeloid leukemia progression
• Michael Malloy: Loss of transcription factor myb drives an immune differentiated megakaryocyte phenotype
• James Palis: A flk-independent pathway of megakaryopoiesis is differentially responsive to stress and can produce high proportions of functionally distinct platelets
• Patrick Reagan: Phase 2 trial of polatuzumab vedotin, rituximab and dose attenuated CHP in patients 75 years and older with large B-cell lymphoma
• Patrick Reagan: Patient characteristics and treatment outcomes with Pola-R-CHP: A real-world study of patients with previously untreated diffuse large B-cell lymphoma (DLBCL) in the United States (US)
• Patrick Reagan: Patterns of care and outcomes in patients with large B-cell lymphoma not treated with full-dose anthracycline regimens: Outcome analysis from the lymphoma epidemiology of outcomes (LEO) prospective cohort study
• Majed Refaai: Evaluating leukemogenic transmission via blood transfusion from genetically modified leukemic mice to healthy recipients
• Shad Yasar: Underexplored mutations in plasma cell myeloma
• Tianming Zhao: Inflammatory and oxidative stress biomarkers associated with cognitive function in patients with Hodgkin lymphoma treated with chemotherapy

Melissa Loh, MD, and Jason Mendler, MD

Oral presentations – co-authors

• Jeevisha Bajaj and Christina Kaszuba, Presented by University Health Network, Toronto: IFN-γ drives long-term bone marrow niche dysfunction following chemotherapy
• Paul Barr, Presented by Oxford University: Pirtobrutinib outcomes in second-line (2L) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) after first-line (1L) cBTKi therapy: A pooled analysis from the BRUIN LOXO-BTK18001 and BRUIN CLL-321 studies
• John Bennett, Presented by Icahn School of Medicine: Bone marrow biopsy characteristics at nadir after intensive induction therapy do not predict outcomes in acute myeloid leukemia (AML): An analysis of ECOG-ACRIN clinical trials
• Richard Burack and Patrick Reagan, Presented by Dana-Farber: Relapsed diffuse large B-cell lymphoma is shaped by molecular subtypes and genomic alterations
• Carla Casulo, Presented by Rutgers: The use and safety of peripheral intravenous catheters (PIV) vs central venous catheters (CVC) for lymphoma patients receiving frontline anthracycline-based chemotherapy: A large multicenter real-world analysis (RWA)
• Carla Casulo, Presented by Mayo Clinic: Outcomes in the 2nd decade following follicular lymphoma (FL) diagnosis: Long-term follow-up from the university of Iowa/Mayo Clinic SPORE molecular epidemiology resource (MER)
• Andrew Evans, Presented by Mass General: ALK+ LBCL and PBL share a similar plasmablastic transcriptional identity but show divergent signaling dependencies and therapeutic vulnerabilities
• Andrew Evans, Presented by Winship: Novel immune gene expression signature risk-stratifies Mantle Cell Lymphoma outcomes independent of TP53 status
• Jonathan Friedberg, Presented by Dana-Farber: Circulating tumor DNA analyses of molecular tumor burden are superior to PET-assessed responses in patients with advanced stage classic Hodgkin lymphoma treated on SWOG S1826
• Jonathan Friedberg and Carla Casulo, Presented by City of Hope: 3-year follow-up of the S1826 study confirms improved progression-free survival with nivolumab-AVD compared to brentuximab vedotin-AVD in advanced stage classic Hodgkin lymphoma
• Jonathan Friedberg and Patrick Reagan, Presented by Sylvester Comprehensive Cancer Center: Outcomes of T-cell/histocyte-rich large B-cell lymphoma (THRLBCL): An international LEO/MER and NiHiL collaborative study
• John Horan, Presented by Boston Children's: Discovery of the transcription factor ZNF683/hobit as a central regulator of pathogenic T cell proliferation in acute gvhd
• John Horan, Presented by Harvard: T cell receptor costimulation blockade effectively prevents acute graft versus host disease without reducing the size or diversity of the T cell immune repertoire
• Kristen O'Dwyer, Presented by UCSF: Pre- or post-CAR-T allogeneic hematopoietic cell transplant provides relapse-free survival benefit for R/R Philadelphia negative B-cell acute lymphoblastic leukemia (B-ALL) successfully treated with brexucabtagene autoleucel in the real world
• Kristen O'Dwyer, Presented by Mayo Clinic: Prospective study of patient-reported depression, and cognitive and functional impairment, and impact on survival and induction mortality in fit adults age ≥60 years receiving intensive chemotherapy (IC) for Acute Myeloid Leukemia (AML): Prospective geriatric assessment (GA) report from ECOG-ACRIN (EA) E2906 randomized study
• Patrick Reagan, Presented by Stanford: A Phase 1 study of KITE-753 or KITE-363 in patients with relapsed/refractory B-cell lymphoma: Initial safety and preliminary efficacy of KITE-753 and updated results of KITE-363
• Patrick Reagan and Jonathan Friedberg, Presented by First Faculty of Medicine, Charles University, Czech Republic: Optimizing risk stratification in patients aged 80+ years with large B-cell lymphoma: Comparison of prognostic indices in three pooled international cohorts
• Matthew Rice, Presented by Feinstein Institutes for Medical Research: Loss of serine threonine protein kinase 25 (STK25) in the bone marrow niche attenuates g/CSF- and TLR7-induced emergency myelopoiesis and mobilization into the periphery
• Danielle Wallace, Presented by MSK: Real-world outcomes of frontline polatuzumab-rchp and impact of frailty in older adults with diffuse large B-cell lymphoma
• Danielle Wallace, Presented by Columbia: Multicenter real-world outcomes in limited stage (LS) diffuse large B-cell lymphoma (DLBCL) treated with abbreviated immunochemotherapy
• Bret Wankel and Paul  Barr, Presented by University of Washington: Superior real-world outcomes of lisocabtagene maraleucel in chronic lymphocytic leukemia

Poster co-authors

• Vikas Arige and David Yule, Presented by University of Pennsylvania, Philadelphia: Somatic mutation discovery in idiopathic multicentric castleman disease (iMCD) lymph node tissue identifies dysregulated intracellular calcium signaling as a potential disease mechanism and therapeutic target
• Paul Barr, Presented by AbbVie, Inc: Evaluation of ventoclax initiation prophylaxis and monitoring outcomes at each dose level and time point in patients with chronic lymphocytic leukemia: A real-world experience
• Richard Burack, Presented by Mayo Clinic: FLP-R: A clinical prediction model for follicular lymphoma Prognosis in the Relapsed/refractory setting
• Ali Al-Darobi and Matthew Ulrickson, Presented by MSK: Patient characteristics, toxicity, and response after real world administration of obecabtagene autoleucel and brexucabtagene autoleucel for relapsed acute lymphoblastic leukemia: A rocca analysis
• Andrew Evans, Presented by Duke: Identifying biological differences between two clinical risk groups of cutaneous CD30+ T cell lymphoproliferative disorders
• Andrew Evans, Presented by Sylvester Comprehensive CC: Genomic and transcriptomic landscape of extranodal marginal zone lymphoma
• Hayley Flanagan, Presented by MD Anderson: Real-world clinical outcomes with novel agent combination therapies for the frontline treatment of pediatric and adult advanced-stage Hodgkin lymphoma
• Jamie Flerlage, Presented by Stanford: Multimodal discovery of distinct tumor ecosystems for classic Hodgkin lymphoma
• Jamie Flerlage, Presented by University of Utah: Age-related differences in presentation among pediatric, adolescent, and young adults with mixed cellularity vs. nodular sclerosis histology Hodgkin lymphoma on Children's oncology group treatment and registry trials
• Jonathan Friedberg, Presented by Washington University: Interim and end-of-treatment FDG-PET demonstrate limited ability to predict 3-year progression-free survival with nivolumab-AVD in first-line treatment of advanced stage Hodgkin lymphoma: Imaging sub-analysis of Phase 3 S1826 study
• Jonathan Friedberg, Presented by First Faculty of Medicine, Charles University and General Hospital, Prague, Czech Republic: Prognostic impact of diagnosis-to-treatment interval in follicular lymphoma patients treated with immunochemotherapy: Evidence from an international cohort with independent validation
• Jonathan Friedberg, Presented by MD Anderson Cancer Center: Survival difference among patients with large B-cell lymphoma (LBCL) based on first-line clinical trial participation: A multi-institutional analysis of 8 academic institutions in the lymphoma epidemiology of outcomes (LEO) cohort
• Jonathan Friedberg, Presented by Dana-Farber: Prognostic impact of Mantle Cell Lymphoma frontline induction response assessments in the ECOG-ACRIN E1411 study of bendamustine-rituximab +/- bortezomib and maintenance with rituximab +/- lenalidomide
• Jonathan Friedberg, Presented by McGill University: The influence of age on patient-reported outcomes (PROs) endpoints on the S1826 crossnetwork Phase III trial of advanced-stage, classic Hodgkin lymphoma (cHL)
• John Horan, Presented by University of Calgary: Children and adolescents with sickle cell disease demonstrate improved health-related quality of life and low decisional regret after hematopoietic cell transplantation: A sickle cell transplant advocacy and research alliance (STAR) study
• John Horan, Presented by Baylor College of Medicine: Provider practices and preparedness for gene therapy in pediatric sickle cell disease: A national survey of pediatric hematologists
• Jane Liesveld, Presented by Washington University: A randomized study of conventional chemotherapy +/- uproleselan in older adults with Acute Myeloid Leukemia receiving intensive induction chemotherapy (Alliance A041701)
• Brea Lipe, Presented by Institute Català d'Oncologia - Hospital Duran I Reynals, L'Hospitalet del Llobregat, Barcelona, Spain: Iberdomide plus daratumumab and dexamethasone (Biard) in patients with newly diagnosed multiple myeloma by renal function: A subgroup analysis of the CC-220-MM-001 trial
• Brea Lipe, Presented by University College London Hospital, London, United Kingdom: Utility and sensitivity of wett-SA53 to measure dysgeusia associated with teletimer, a GPRC5D×CD3 bispecific antibody, in Relapsed/Refractory multiple myeloma: Preliminary data from the talisman study
• Marissa Locastro, Presented by UNC Chapel Hill: Measuring patient preference information for blood cancer treatments and outcomes: A systematic review and meta-analysis
• Melissa Loh, Presented by UNC Chapel Hill: Creating a tool for measuring preferences for treating blood cancers in older adults using implementation science
• Melissa Loh, Presented by Buffett Cancer Center University of Nebraska: Treatment selection and functional outcomes in treatment-related acute myeloid leukemia (tam) and AML with myelodysplasia-related changes (MRC): A multicenter prospective cohort study
• Nicole Michmerhuizen, Presented by St. Jude Children's: Ectopic BCL11B disrupts the activity of early hematopoietic transcription factors to skew lineage commitment
• Craig Mullen, Presented by University of Alabama at Birmingham: Relationship of sociodemographic factors to presentation and natural history of provoked venous thromboembolism in U.S. children: A secondary analysis of the multinational kids-DOTT trial
• Kristen O'Dwyer, Presented by University of Alabama at Birmingham: Clinical trial availability and receipt of guideline concordant care among adolescents and young adults (AYAs) with acute lymphoblastic leukemia
• Kristen O'Dwyer, Presented by Cleveland Clinic: SWOG 1318: Combination of dasatinib, prednisone, and blinatumomab for older patients with Philadelphia chromosome positive acute lymphoblastic leukemia: longer follow up and predictors of outcomes
• Kristen O'Dwyer, Presented by University of Chicago: Trial in progress: A Phase I/II study to investigate the combination of LP-118, ponatinib, vincristine and dexamethasone (LPVd regimen) in relapsed/refractory T-ALL/lbl
• Archibald Perkins, Presented by Université Paris Cité: Distinct roles of fetal hematopoietic stem and progenitor cells in building the immune system
• Pat Reagan, Presented by Cabaletta Bio, Philadelphia: Mechanistic basis of the acute safety profile of rese-cel, an autologous CD19-CAR T, in patients with autoimmune disease treated in four ongoing phase 1/2 clinical trials
• Pat Reagan, Presented by University Medical Center Groningen, Netherlands: Two-year update of ZUMA-2 Cohort 3: Brexucabtagene autoleucel (Brexu-cel) in patients (pts) with relapsed/refractory mantle cell lymphoma (R/R MCL) who had not received prior Bruton tyrosine kinase inhibitor (BTKi) therapy
• Patrick Reagan, AnnaLynn Williams, and Jonathan Friedberg, Presented by First Faculty of Medicine, Charles University, Czech Republic: Predictive performance of the LEO comorbidity index in patients aged 80+ years with large B-cell lymphoma
• Patrick Reagan, Presented by City of Hope National Medical Center: Multi-center real world analysis of treatment outcomes of non-COVALENT btki, pirtobrutinib, in patients with COVALENT btki relapsed/refracdtory Mantle Cell Lymphoma
• Patrick Reagan and Jonathan Friedberg, Presented by First Faculty of Medicine, Charles University, Czech Republic: Treatment patterns in patients aged 80+ years with LBCL: Propensity score analysis reveals comparable outcomes between R-CHOP and R-mini-CHOP
• Danielle Wallace: Patterns of care in second line management of nodal peripheral T-cell lymphoma from the lymphoma epidemiology of outcomes (LEO) and molecular epidemiology resource (MER) prospective cohort Study
• Danielle Wallace and Jonathan Friedberg, Presented by Enterome, Paris, France: EO2463 (EO) peptide immunotherapy combined with rituximab (R) for first-line treatment of low-tumor burden follicular lymphoma (FL): A feasibility evaluation in Study EONHL1-20/sidney (NCT04669171)
• Danielle Wallace, Presented by Winship: Diagnostic and therapeutic patterns in cutaneous T-cell lymphomas (CTCL): Real-world data from the lymphoma epidemiology outcome-molecular epidemiology resource (LEO-MER) prospective cohort study.
• Danielle Wallace, Presented by Mayo Clinic: EO2463 (EO) peptide immunotherapy in patients (pts) with newly diagnosed asymptomatic follicular lymphoma (FL) and marginal zone lymphoma (MZL): Study EONHL1-20/sidney (NCT04669171) primary endpoint lugano objective response analysis
• Danielle Wallace, Presented by Mayo Clinic: Shorter diagnosis to treatment interval is associated with poor prognosis in patients with peripheral T-cell lymphoma: Analysis from the LEO and MER cohorts
• Danielle Wallace, Presented by University of Colorado: Comparison of real-world survival outcomes and time toxicity of CAR T-cell versus bispecific antibody therapies in relapsed/refractory follicular lymphoma: A multicenter cohort from 15 US academic institutions
• AnnaLynn Williams and Jonathan Friedberg, Presented by UCO Ematologia Azienda Sanitaria Giuliano Isontina (ASUGI), Trieste, Italy: Survival differences in metropolitan versus nonmetropolitan/rural counties in the US: An analysis according to rural-urban continuum codes (RUCC) in the lymphoma epidemiology of outcomes (LEO) study cohort
• Clive Zent, Nydia Jaimes-Delgado, and Charles Chu, Presented by University of South Alabama: Dual pathways of antibody-dependent phagocytosis: Distinct kinetics, finite capacities, and therapeutic implications
• Clive Zent, Philip Rock, Richard Burack, and Charles Chu, Presented by Centre for Research and Technology Hellas, Greece: Dissecting the biology of hairy cell leukemia variant: Insights from whole exome and RNA sequencing