Investigators from the Mass General Brigham healthcare system will present research discoveries and outcomes from clinical trials at the 2024 American Society of Hematology (ASH) Annual Meeting, held December 7-10, 2024, in San Diego.
ASH brings together leading experts in classical and malignant blood diseases to share the latest breakthroughs, clinical studies and research impacting the field and patient care. Mass General Brigham researchers from Massachusetts General Hospital and Brigham and Women’s Hospital will cover a wide range of topics, including a plenary session on immune thrombocytopenia, early phase and investigational therapies, myeloproliferative syndromes, advances in treatment of lymphomas and leukemias, and more.
Below are selected highlights from this year’s top presentations.
When: Saturday, December 7, 12:30 PM ET
Who: Antonio Pedro Amaro Ferreira, PhD, Brigham and Women’s Hospital
What: Lymph nodes (LNs) are secondary lymphoid organs where lymphocytes interact with antigen-presenting cells to initiate adaptive immune responses within microenvironments established by resident stromal cells. LNs are also the major sites of follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL) growth. These two B cell neoplasms alter the stromal architecture of LNs in highly stereotypical ways that are thought to be critical to facilitate their growth and survival. To investigate the tumor microenvironment in FL and CLL, Dr. Ferreira and team developed a comprehensive single-cell RNA sequencing pipeline to analyze all resident LN cells. This method involved independently sorting CD45+ (immune/hematopoietic) and CD45- cells (non-hematopoietic stroma), allowing the detailed examination of the gene expression profiles of the immune and non-hematopoietic stromal compartments. Their findings revealed that the proliferation of FL and CLL cells within specialized niches is associated with a transient upregulation of MYC, subsequent downregulation of which may act to limit the growth potential of these indolent neoplasms.
When: Sunday, December 8, 1 PM ET
Who: Salvia Jain, MD, Senior Author, Massachusetts General Hospital
What: The variability in global access to medications and treatment practices make it challenging to evaluate the benefits of contemporary therapies for patients with relapsed and refractory (R/R) mature T-cell and NK-cell lymphomas (MTCL and MNKCL). While numerous prognostic factors and models have been suggested to categorize the risk levels of patients with MTCL and MNKCL, they have primarily been developed for newly diagnosed patients. On the other hand, for the common subtypes of R/R MTCL and MNKCL patients, the identification of risk factors and subgroups that lead to variability in treatment outcomes and overall survival is still not well established. Thus, a new prognostic model is needed to further refine subgroups with varied outcomes in R/R patients. Dr. Jain and team conducted an international retrospective cohort study of 925 patients with R/R MTCL and MNKCL diagnosed between January 2010 and September 2021, who received either “novel” single agent or cytotoxic chemotherapy for second-line treatment from 13 institutions representing 10 countries. In summary, the team developed a new prognostic scoring system for patients with R/R MTCL and MNKCL that was validated in training, testing and independent datasets that has enabled their segregation and has the potential to facilitate clinical decision.
When: Sunday, December 8, 5 PM ET
Who: David Kuter, MD, DPhil, Massachusetts General Hospital
What: Patients with primary ITP who are not sufficiently responsive or intolerant to available therapies experience higher rates of morbidity, mortality, and impaired quality of life (QoL). Phase 2 results with covalent, reversible BTKi rilzabrutinib in ITP showed rapid and durable platelet responses with favorable safety. The phase 3 LUNA 3 study enrolled adults ≥18 years old and pediatrics 10-<18 years old with primary persistent/chronic ITP and platelet counts <30×109/L within two weeks of study initiation. As of March 14, 2024, 202 randomized adults (n=133 rilzabrutinib, n=69 placebo) had a similar overall median baseline age of 47 years old, median baseline platelet count of 15×109/L, and 46% received ≥5 prior ITP therapies (including 28% splenectomized in both arms). Dr, Kuter and team found that first-in-class BTKi rilzabrutinib has a robust therapeutic effect in patients with ITP as shown by rapid and durable platelet response, reduced bleeding and need for rescue therapy, improved physical fatigue and QoL, and favorable safety and tolerability.
When: Sunday, December 8, 1:15 PM ET
Who: Jeremy Abramson, MD, Massachusetts General Hospital
What: Brentuximab vedotin (BV) in combination with doxorubicin, vinblastine, and dacarbazine (AVD) is approved for patients with advanced classical Hodgkin lymphoma (cHL). A study in non-bulky, early-stage cHL showed preserved efficacy with improved safety when omitting vinblastine in the BV+AD regimen (Blood Adv. 2023;7[7]:1130-1136). Initial results from the phase 2 SGN35-027 part C study, with a median follow-up of 16.5 months, showed promising efficacy and an acceptable safety profile for BV and nivolumab in combination with chemotherapy (AN+AD) in patients with non-bulky, early-stage cHL. Dr. Abramson and team found that this updated analysis from the SGN35-027 part C study demonstrated continued efficacy of this novel regimen, sparing bleomycin, vinblastine, and radiation, in early-stage cHL, with a CR rate of 92% and 36-month PFS rate of 95%. The safety profile remains favorable and consistent with that in the prior analysis. Long-term results from this study support the use of BV and nivolumab in combination with limited chemotherapy in patients with non-bulky, early-stage cHL.
When: Monday, December 9, 8:15 PM ET
Who: Jacob Soumerai, MD, Massachusetts General Hospital
What: The combination of venetoclax, a BCL2 inhibitor, with ibrutinib, a BTK inhibitor, is effective in chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), but their clinical use can be limited by toxicity. Sonrotoclax (BGB-11417), a next-generation BCL2 inhibitor, is a more selective and more pharmacologically potent inhibitor of BCL2 than venetoclax, with a shorter half-life and no drug accumulation. In this study, patients received zanubrutinib (320 mg once daily or 160 mg twice daily) for 8-12 weeks, then added sonrotoclax using a ramp-up schedule (weekly or daily) to the target doses (160 or 320 mg QD) to mitigate risk of tumor lysis syndrome. Patients were treated until progression, unacceptable toxicity, or could elect to stop after 96 weeks (24 cycles) of treatment. TLS was assessed per Howard (2011) criteria. Dr. Soumerai and team found that Sonrotoclax (160 and 320 mg) in combination with zanubrutinib was safe and well-tolerated in patients with tumor-node CLL/SLL.
Myeloproliferative Syndromes and Chronic Myeloid Leukemia: Basic and Translational: New Insights into The Biology of Myeloproliferative Syndromes
When: Monday, December 9, 6 PM ET
Who: Benjamin Rolles, MD, Brigham and Women’s Hospital
What: Although the inferred “fitness” of clonal hematopoesis (CH) driver mutations differs depending on the gene mutation, the impact of environmental factors that may promote or impair CH expansion remains largely unknown. Dr. Rolles and team hypothesized that obesity influences the clonal expansion rate of common CH driver mutations. To test this hypothesis, they first interrogated data from the UKBiobank (UKBB) (n=425,573 exomes) to evaluate the relationship between body mass index (BMI) (kg/m2) and four common CH mutations, namely DNMT3A, TET2, ASXL1, and JAK2. In UKBB analyses, they identified genotype-specific patterns of association between BMI and the presence of CH mutations. Dr. Rolles’ study is the largest to date to evaluate the relationship between obesity and CH and the first to investigate the negative association between JAK2V617F CH and obesity, using functional studies. The team also found that transcriptomic profiling points to activation of the interferon signaling pathway in Jak2-mutant HSC as a possible mechanism by which JAK2-mutant LT-HSC may preferentially exhaust during obesity. These findings support testing pegylated interferon as a potential treatment for individuals with JAK2-mutant CH and a clinical protocol is currently under development.
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