Hematologists and oncologists from UCSF Health showcased groundbreaking research and clinical findings at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego, addressing critical advancements in hematologic malignancies and related disorders. The presentations covered a range of topics, including gene editing, inflammation's role in hematopoiesis, AI-driven relapse prediction, and novel therapeutic combinations.
Gene Editing Technologies to Improve CAR T-cell Function
Justin Eyquem, PhD, presented his latest work on novel gene editing technologies to enhance CAR T-cell function and facilitate their manufacturing. His presentation, "New Gene Editing Technologies," highlighted new gene edits associated with improved CAR T-cell functional persistence and novel types of vectors for generating CAR T cells in vivo. The research aims to improve the efficacy and scalability of CAR T-cell therapies, offering potential benefits for patients with various hematologic cancers.
Inflammation's Role in Hematopoietic Homeostasis
Serine Avagyan, MD, PhD, co-chaired and presented on "Inflammation As a Regulator of Hematopoietic Homeostasis in Clonal Selection." She discussed the role of inflammatory pathways in the developmental origins of hematopoietic stem and progenitor cells (HSPCs) and in shaping postnatal blood cell production (hematopoiesis) in the context of aging and genetic blood disorders. Her talk highlighted recent studies investigating how inflammation affects the fate of normal and mutant HSPCs, and the pathways by which inflammatory exposure affects the selection of mutant HSPC clones due to differential clonal fitness. These insights could lead to new therapeutic strategies targeting inflammatory pathways to prevent or treat blood disorders.
AI Predicts Early Relapse in DLBCL Patients Post-CAR T-cell Therapy
Michelle Wang, PharmD, PhD, presented a study that developed a clinically interpretable decision tree machine learning (ML) model to identify patients with risks of early relapse of their disease within six months after receiving axicabtagene ciloleucel (axi-cel) for relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The study, which evaluated real-world safety and effectiveness of axi-cel in a multi-center population across the University of California Health System, found that the ML model could effectively predict early relapse, potentially allowing for earlier intervention and improved outcomes. Nearly 60% of patients receiving axi-cel eventually experience relapse, with most requiring additional therapies.
Combination of Glofitamab with Pirtobrutinib in Relapsed/Refractory Mantle Cell Lymphoma
Madhav Seshadri, MD, and Charalambos Andreadis, MD, presented a poster on their trial evaluating the combination of glofitamab with pirtobrutinib in BTK inhibitor (BTKi)-naive or BTKi-intolerant patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL). The investigators are evaluating a regimen which they anticipate will be tolerable and highly active in R/R MCL, with the potential for measurable residual disease-guided, limited-duration therapy. The trial, conducted through the University of California Hematologic Malignancies Consortium, aims to provide a more effective and tolerable treatment option for patients with MCL.
Efficacy and Safety of Teclistamab in Triple-Class Exposed Multiple Myeloma
Thomas G. Martin, MD, presented pooled data from three clinical studies, including 217 patients, demonstrating the efficacy and safety of teclistamab in patients with triple-class exposed relapsed/refractory multiple myeloma (RRMM). Teclistamab, a BCMA x CD3 bispecific antibody, has shown rapid, deep, and durable responses with a manageable safety profile. These findings reinforce teclistamab as a valuable treatment option for patients with heavily pre-treated multiple myeloma.
Delayed Neurotoxicity after CAR-T in Multiple Myeloma
Anupama Deepa Kumar, MD, and Ajai Chari, MD, presented results from a Global IMWG Registry on delayed neurotoxicity after CAR-T in multiple myeloma. The study looked at emerging evidence of rare subacute to late neurological toxicities (NTs) after BCMA CAR T-cell therapy (CAR-T) in multiple myeloma (MM). The team retrospectively established a registry of NTs via the Immune Therapy Working Committee of the International Myeloma Working Group, gathering data pertaining to demographics, MM characteristics, MM response, NT signs/symptoms, diagnostic workup and treatment. The findings highlight the importance of monitoring for and managing potential neurological complications following CAR-T therapy.
