Advertisement


Tomohiro Aoki, MD, PhD, on the Spatial Tumor Microenvironment and Outcome of Relapsed/Refractory Classical Hodgkin Lymphoma

2022 ASH Annual Meeting and Exposition

Advertisement

Tomohiro Aoki, MD, PhD, of the University of British Columbia and the Centre for Lymphoid Cancer at BC Cancer, discusses a novel prognostic model applicable to patients with relapsed or refractory classical Hodgkin lymphoma who were treated with autologous stem cell transplantation. The model has shown the interaction between the biomarker CXCR5 on HRS cells (Hodgkin and Reed/Sternberg cells, hallmarks of Hodgkin lymphoma) with specific follicular T helper cells and macrophages, a prominent crosstalk axis in relapsed disease. This insight opens new avenues to developing predictive biomarkers (Abstract 71).

 



Transcript

Disclaimer: This video transcript has not been proofread or edited and may contain errors.
Development of the spatially informed biomarker, that is the main goal of our study. Our study here is focusing on relapsed refractory Hodgkin lymphoma because, as you know, despite the recent treatment advancements, still about 20 to 30% of patients experience relapsed disease, and about half of them eventually succumb to their disease. Importantly, there's no biomarker we can utilize in daily clinical practice setting yet. So, our study goals are describing the tumor microbiome ecosystem for the relapsed/refractory Hodgkin lymphoma and develop some novel prognostic model for relapsed/refractory Hodgkin lymphoma. For these goals, we applied imaging mass cytometry, which enabled us to visualize more than 37 protein marker in the spatial context, and we applied IMC using the unique cohorts, which consist of 73 paired diagnostic and relapsed biopsy of Hodgkin lymphoma. Primary advantage of the imaging mass cytometry data is that we can capture the complex spatial information at single cell resolutions. To capture the complex information, we established the pipeline called spatial score, so that we can utilize the information for the biomarker development. First, we describe the unique contrast between early relapsed biopsy and relapse biopsy. In brief, we identified that early relapsed biopsy, in general, shares micro-environment patterns between diagnostic and relapsed biopsy. In contrast, where relapsed biopsy shows the significant difference between diagnostic and relapsed biopsies. Next, we sought to develop the micro-environments best prognostic model, using the spatial information. So first, using the best model and using amazing math rudimentary data, we identified the four variables which is significantly associated with the outcome in relapsed/refractory Hodgkin lymphoma which includes CXCR5 positive HRS cells, CD4 positive T cells, macrophage and CXCR5 positive B cell population. Using those four variables, we have developed a novel prognostic model called RHL4S, which produced highly significant [inaudible 00:02:50] group in relapsed/refractory Hodgkin lymphoma, in harmony, treated with high dose chemotherapy, followed by stem cell transplantation. We further identified the unique micro-environment patterns of the six certified positive HRS cells, which are spatially arranged together and form cell clusters. Their unique interactions with the six certified positive initial population, including macrophage and T cells. In summary, we have developed a novel prognostic model in relapsed/refractory Hodgkin lymphoma and importantly, we have now opened up a new avenue of spatially informed biomarker. I believe that this new concept can be applicable to any of the cancer types, not limited to Hodgkin lymphoma. Now, we are verifying our findings and our ultimate goal is we can utilize those spatially informed biomarker in the daily clinical practice setting. Now we are translating our IMC data findings into the managed IT settings so that we can utilize the information into the daily clinical practice.

Related Videos

Hematologic Malignancies
Genomics/Genetics

Smita Bhatia, MD, MPH: Some Clonal Mutations May Predict Therapy-Related Myeloid Neoplasms

Smita Bhatia, MD, MPH, of the Institute for Cancer Outcomes and Survivorship, University of Alabama at Birmingham, discusses study findings that showed key somatic mutations in the peripheral blood stem cell product increases the risk of developing therapy-related myeloid neoplasms (Abstract 119).

Leukemia
Lymphoma

Jennifer R. Brown, MD, PhD, on CLL/SLL: New Findings on Zanubrutinib vs Ibrutinib for Relapsed or Refractory Disease

Jennifer R. Brown, MD, PhD, of Dana-Farber Cancer Institute, discusses phase III findings of the ALPINE study, which showed that zanubrutinib is more efficacious and better tolerated than ibrutinib as a treatment for patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). In this first head-to-head comparison of the two BTK inhibitors, the superior progression-free survival of zanubrutinib was observed across all major subgroups, including high-risk patients (Abstract LBA-6).

Leukemia

Jorge E. Cortes, MD, on CML: Efficacy and Safety of Vodobatinib

Jorge E. Cortes, MD, of Georgia Cancer Center at Augusta University, discusses new findings on vodobatinib, which was administered to patients with chronic-phase Philadelphia chromosome–positive chronic myeloid leukemia (CML) and appeared to be efficacious and safe in people who had received therapy with two or three prior tyrosine kinase inhibitors (TKIs). Vodobatinib remains a potential option for these highly refractory patients. A phase II study (NCT02629692) of vodobatinib is ongoing in CML patients whose disease has failed to respond to three or more TKIs, including ponatinib (Abstract 84).

Leukemia
Genomics/Genetics

Irene Roberts, MD, on Leukemogenesis in Infants With Trisomy 21

Irene Roberts, MD, of Oxford’s Weatherall Institute of Molecular Medicine, discusses children with Down syndrome, who have a more than 100-fold increased risk of developing acute myeloid leukemia before their fourth birthday compared to children without Down syndrome. Their risk of acute lymphoblastic leukemia is also increased by around 30-fold. Dr. Roberts details current knowledge about the biologic and molecular basis of this relationship between leukemia and Down syndrome, the role of trisomy 21 in leukemogenesis, and the clinical implications of these findings.

Lymphoma
Genomics/Genetics

Stephen M. Ansell, MD, PhD, and Patrizia Mondello, MD, PhD: New Findings on How the IRF4 Gene Shapes Tumor Immunity in Follicular Lymphoma

Stephen M. Ansell, MD, PhD, and Patrizia Mondello, MD, PhD, both of the Mayo Clinic, discuss the 20% of patients with follicular lymphoma (FL) who relapse early and experience a poor prognosis. The researchers found that FLs with high levels of IRF4 expression are associated with a suppressive tumor microenvironment, and selective IRF4 silencing restores antilymphoma T-cell immunity. Further investigation is warranted to identify the mechanisms by which IRF4 controls tumor immunity to develop precision therapies for this population (Abstract 70).

Advertisement

Advertisement




Advertisement