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
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.
The ASCO Post Staff
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).
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
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).
The ASCO Post Staff
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).
The ASCO Post Staff
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).