Advertisement


Eileen M. Boyle, MD, PhD, on Multiple Myeloma: Sustained MRD Negativity in Newly Diagnosed Disease Treated with Immunotherapy Regimens

2022 ASH Annual Meeting and Exposition

Advertisement

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).



Transcript

Disclaimer: This video transcript has not been proofread or edited and may contain errors.
In our study, we attempted to deconvolute the microenvironment of multiple myeloma patients in order to understand what were the determinants of response. Because as you know, there's 30% of patients that will not respond or will not achieve MRD negativity upfront in myeloma. So in order to do that, we performed single-cell analysis on 20 patients, both at diagnosis and after eight cycles of treatment, to try and understand what happened to the immune composition of that environment over time. And we were able to identify different cellular components that will determine how the patient is going to respond. And we were particularly interested in three subtypes of cells: NK cells, monocytes and T-cells. What we saw, it was that the microenvironment was function both of time and the degree of response in the disease. And so we were able to see that, upfront, NK cells were significantly higher in good responders. These NK cells produced interferon gamma and were associated with activated monocytes that had evidence of interferon gamma response. Similarly, we noticed that T-cells that were highly diverse in these patients. But after eight cycles of treatment, these NK cells and monocytes changed in phenotype, disappeared in some cases, and the TCE repertoire became less diverse. In patients that did not achieve MRD negativity, on the other hand, what we saw was there were some [inaudible 00:01:51] there, but they did not display that interfering gamma signature. And the monocytes that were associated with them were in this regulatory calm phase, and the T-cell repertoire was not very diverse. But after eight cycles of treatment, changes did appear, and we did notice that the monocytes attempted to display some evidence of interferon activation, suggesting there was still a chronic antigen stimulations. T-cells were more diverse, suggesting that we did have a microenvironment, after eight cycles of treatment, that could be potentially manipulated in order to improve the depth of response in these poor responders early on. What we need to do with this data is, of course, validate it and use it in order to build better both diagnostic markers early on and potential therapeutic implications that we can use at these cells and manipulate the microenvironment to increase the depth of response in these patients.

Related Videos

Multiple Myeloma
Genomics/Genetics
Immunotherapy

Francesco Maura, MD, on Genomic Determinants of Resistance in Newly Diagnosed Multiple Myeloma Treated With Targeted Immunotherapy

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).

 

Lymphoma

Alex F. Herrera, MD, on Previously Untreated DLBCL: Circulation Tumor DNA and Risk Profiling

Alex F. Herrera, MD, of the City of Hope National Medical Center, discusses results from the POLARIX study, which showed that circulating tumor DNA (ctDNA) analysis has prognostic value for patients with previously untreated diffuse large B-cell lymphoma. Patients who did not achieve 2.5 or greater log-fold change and/or did not have ctDNA clearance following one cycle of polatuzumab vedotin along with rituximab, cyclophosphamide, doxorubicin, and prednisone had inferior outcomes than those who did. Early changes in ctDNA levels may be of use in risk-adapted trial designs to identify patients in need of alternative treatment. (Abstract 542).

Leukemia

Mark R. Litzow, MD, on ALL: Consolidation Therapy With Blinatumomab Improves Overall Survival

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).

Hematologic Malignancies
Immunotherapy

Joseph Schroers-Martin, MD, on Posttransplant Lymphoproliferative Disorders: Tumor Microenvironment Determinants of Immunotherapy Response

Joseph Schroers-Martin, MD, of Stanford University, discusses immunogenomic features reflecting divergent biology in posttransplant lymphoproliferative disorders (PTLD). These include evidence of mismatch repair defects in Epstein-Barr virus–positive PTLD, tumor microenvironment depletion, and MYC pathway enrichment in certain patients (Abstract 72).

Leukemia

Anand P. Jillella, MD, on Acute Promyelocytic Leukemia: A Simplified Patient Care Strategy to Decrease Early Deaths

Anand P. Jillella, MD, of Georgia Cancer Center at Augusta University, discusses results from the ECOG-ACRIN EA9131 Trial, which showed that using a simplified treatment algorithm and management recommendations made by a group of specialists, resulted in a dramatic improvement in 1-year survival of patients with acute promyelocytic leukemia (Abstract 421).

Advertisement

Advertisement




Advertisement