City of Hope, a renowned leader in cancer research and treatment, is poised to unveil groundbreaking advancements in hematologic malignancies at the 2025 American Society of Hematology (ASH) Annual Meeting and Exposition. This prestigious event, set to take place December 6-9 in Orlando and virtually, will gather over 30,000 experts from around the globe, underscoring its status as the world’s premier hematology conference. City of Hope’s extensive contributions span across 105 sessions, spotlighting innovations in blood cancer biology, cellular therapies, and precision medicine tailored to individual patient profiles.
At the forefront of leukemia research, City of Hope will present pivotal results from the Paradigm trial—a phase 2, randomized, multi-center study comparing the efficacy of azacitidine combined with venetoclax against conventional induction chemotherapy in newly diagnosed, fit adults suffering from acute myeloid leukemia (AML). This investigation delves into novel therapeutic regimens aiming to enhance treatment responses while minimizing toxicity profiles. Dr. Ibrahim Aldoss, a distinguished hematologist, leads these efforts to redefine AML management based on molecular and functional disease characteristics.
Another critical leukemia-related highlight involves CD19-directed chimeric antigen receptor (CAR) T cell therapy deployed as a definitive consolidation strategy in older adults diagnosed with B-cell acute lymphoblastic leukemia (b-ALL) in their first complete remission. This advanced immunotherapy modality has demonstrated safety and therapeutic durability in maintaining minimal residual disease (MRD) negativity, a key prognostic marker that correlates with long-term survival. The application of CAR T cells in this demographic represents a transformative approach overcoming limitations traditionally faced by the elderly in tolerating intensive chemotherapy.
In the realm of lymphoma, City of Hope researchers will share a significant three-year follow-up analysis from the S1826 study. This data corroborates the superior progression-free survival observed with the immune checkpoint inhibitor nivolumab combined with the chemotherapy backbone AVD, compared to the brentuximab vedotin-AVD regimen in advanced-stage classic Hodgkin lymphoma. Such findings highlight the potential of harnessing the immune system to enhance frontline cancer control while mitigating treatment-related adverse events. Dr. Alex Herrera, an expert in lymphoma therapeutics, will elucidate these findings and their implications for clinical practice.
Expanding beyond traditional targets, novel BAFF receptor (BAFFR)-CAR T cells, designated PMB-CT01, exhibit promising durable responses and manageable toxicity in patients with relapsed or refractory B-cell lymphomas, including those with prior failure of CD19-directed therapies or CD19-negative disease phenotypes. This advancement underscores the strategic diversification of antigen targets in CAR T cell therapy to circumvent antigen escape and resistance mechanisms intrinsic to B-cell malignancies, an area led by Dr. Elizabeth Budde.
Addressing mantle cell lymphoma, an interim phase II study evaluates the combination of glofitamab, lenalidomide, and venetoclax (GLOVe) in treatment-naïve high-risk patients. Early response and safety metrics post-stage 1 enrollment suggest enhanced therapeutic synergy leveraging an antibody-based bispecific approach alongside targeted agents. Such combination regimens aim to overcome the aggressive biology characterizing mantle cell lymphoma, as presented by Dr. Tycel Phillips.
City of Hope’s expertise extends to multiple myeloma, where research on the safety and efficacy of out-of-specification ciltacabtagene autoleucel (cilta-cel), a BCMA-targeted CAR T cell therapy, addresses challenges inherent in relapsed or refractory disease settings. Dr. Azra Borogovac will present data emphasizing real-world applicability of cellular therapies manufactured under stringent quality parameters, illustrating the balance between regulatory stringency and urgent clinical need.
Transplantation medicine at City of Hope ventures into total marrow and lymphoid irradiation (TMLI) combined with fludarabine-melphalan conditioning for matched donor hematopoietic cell transplantation in older patients with relapsed/refractory hematologic disease. This innovative conditioning regimen offers a refined radiation dose distribution to optimize transplant efficacy and reduce off-target toxicity. Dr. Monzr M. Al Malki’s contributions in refining transplant conditioning protocols address the crucial need to expand transplant candidacy among older and comorbid populations.
Moreover, the institution is pioneering first-in-human trials involving allogeneic CD6-CAR regulatory T cells (tregs) to mitigate chronic graft-versus-host disease (GVHD) following allogeneic hematopoietic cell transplantation. This cellular therapy harnesses immune modulation to restore tolerance and thymic homeostasis, marking a potentially paradigm-shifting approach to one of transplantation’s most formidable complications. Insights into a Toll-like receptor 4 (TLR4) and heat shock protein 70 (HSP70) efferocytic program in thymic macrophages further elucidate mechanisms sustaining thymic output and immune reconstitution, as studied by City of Hope scientists.
Apart from scientific presentations, City of Hope is spearheading educational initiatives critical for disseminating cutting-edge knowledge. The 14th Annual BMT & Cell Therapy Winter Workshop, co-chaired by Dr. Marcel van den Brink, embodies a comprehensive platform addressing emergent themes in cellular therapies and transplantation. Additional symposia explore the latest standards in B-ALL treatment employing off-the-shelf bispecific antibodies and integrate functional with genomic precision medicine in blood cancers, facilitating a multidisciplinary treatment strategy.
A notable scientific workshop led by Dr. Pamela Becker focuses on the integration of functional assays and genomic data, propelling personalized hematologic malignancy therapies from bench to bedside. This synthesis of molecular insights and clinical phenotypes is essential for tailoring interventions that optimize efficacy and curtail resistance. Concurrently, Dr. van den Brink presents novel intersections between the microbiome, diet, and cancer immunotherapy, unveiling how host-environment interactions influence therapeutic outcomes.
In tackling infectious complications post-cellular therapies, educational spotlights led by Dr. Randy Taplitz delineate measures to reduce infection risks in immunocompromised patients. These guidelines are paramount to improving survival and quality of life, given the vulnerability induced by immune ablative treatments and prolonged cytopenias. City of Hope’s multifaceted approach encompasses not only therapeutic innovation but also comprehensive patient care paradigms.
Collectively, City of Hope’s robust presence at ASH 2025 illustrates a commitment to advancing hematology through translational research, precision medicine, and educational leadership. Their integrated model of innovative clinical trials, cutting-edge cellular therapy development, and rigorous biological discovery is setting new benchmarks in blood cancer treatment worldwide. This synthesis of expertise and technology promises to reshape therapeutic landscapes and deliver hope to patients battling some of the most challenging malignancies.
Subject of Research: Hematologic malignancies including leukemia, lymphoma, multiple myeloma, and transplantation therapies.
Article Title: City of Hope Unveils Transformative Advances in Blood Cancer Therapies at ASH 2025
News Publication Date: December 2024
Web References:
https://www.cityofhope.org/about-city-of-hope/leadership-team/marcel-van-den-brink
https://submit.hematology.org/program/session/117545
https://www.cityofhope.org/patients/find-a-doctor/ibrahim-aldoss
https://www.cityofhope.org/patients/find-a-doctor/alex-herrera
https://www.cityofhope.org/patients/find-a-doctor/elizabeth-budde
https://www.cityofhope.org/patients/find-a-doctor/tycel-phillips
https://www.cityofhope.org/patients/find-a-doctor/lindsey-murphy
https://www.cityofhope.org/patients/find-a-doctor/azra-borogovac
https://www.cityofhope.org/patients/find-a-doctor/monzr-al-malki
https://www.cityofhope.org/patients/find-a-doctor/amandeep-salhotra
https://www.cityofhope.org/patients/find-a-doctor/pamela-becker
https://www.cityofhope.org/patients/find-a-doctor/randy-taplitz
Keywords: Hematology, Blood cancer, Leukemia, Lymphoma, Multiple myeloma, Cancer immunology, Cellular therapies, CAR T cell therapy, Hematopoietic cell transplantation, Precision medicine, Immunotherapy, Graft-versus-host disease
