Tomohiro Aoki, MD, PhD, on the Spatial Tumor Microenvironment and Outcome of Relapsed/Refractory Classical Hodgkin Lymphoma
2022 ASH Annual Meeting and Exposition
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
The ASCO Post Staff
Eileen M. Boyle, MD, PhD, of the Perlmutter Cancer Center, NYU Langone Health, discusses Fc-mediated antibody effector function, inflammation resolution, and oligoclonality and their role in predicting sustained measurable residual disease negativity in patients with newly diagnosed multiple myeloma who were treated with immunotherapy regimens. For the first time, an analysis of T-cell receptors shows that oligoclonal profiles seen on treatment may influence the fitness of the immune response (Abstract 100).
The ASCO Post Staff
Paul G. Richardson, MD, of the Dana-Farber Cancer Institute, discusses preliminary results from the dose-expansion phase of the CC-92480-MM-001 Trial, which showed promising efficacy in patients with relapsed and refractory multiple myeloma, including those with prior BCMA-targeted therapies. Patients in these two groups had an overall response rate of 40% and 50%, respectively. The results support the development of mezigdomide, currently being evaluated in combination with standard therapies in multiple myeloma as part of a large, ongoing phase I/II trial (NCT03989414) and planned phase III studies (Abstract 568).
The ASCO Post Staff
Mark R. Litzow, MD, of the Mayo Clinic, discusses phase III results from the ECOG-ACRIN E1910 Trial, which show that adding blinatumomab to consolidation chemotherapy resulted in a significantly better overall survival in adult patients aged 30 to 70 years with newly diagnosed B-lineage acute lymphocytic leukemia (ALL) who were measurable residual disease–negative after receiving intensification chemotherapy. The authors believe this may represent a new standard of care for this population (Abstract LBA-1).
The ASCO Post Staff
Paolo F. Caimi, MD, of the Taussig Cancer Institute, Cleveland Clinic, discusses new findings showing that patients with diffuse large B-cell lymphoma (DLBCL) who achieve a complete response after salvage therapy with rituximab, ifosfamide, carboplatin, and etoposide (R-ICE) can achieve long-term disease control, regardless of the time to relapse from initial therapy, particularly if they proceed to autologous stem cell transplant (ASCT). These results suggest that second-line chemotherapy followed by ASCT and/or CAR T-cell therapy for chemosensitive and chemorefractory patients may maximize patient outcomes, regardless of time to relapse (Abstract 156).
The ASCO Post Staff
Francesco Maura, MD, of the University of Miami, Sylvester Comprehensive Cancer Center, discusses his team’s findings in which they defined a comprehensive catalogue of genomic determinants of response to DKRd (carfilzomib, lenalidomide, dexamethasone) in newly diagnosed multiple myeloma. The researchers have identified a number of new genomic alterations that explain resistance to the agents currently used in combination regimens (Abstract 470).
