Francesco Maura, MD, on Genomic Determinants of Resistance in Newly Diagnosed Multiple Myeloma Treated With Targeted Immunotherapy
2022 ASH Annual Meeting and Exposition
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).
Transcript
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
The study was, the purpose was to identify mechanism or resistance to a combination of drugs called quadruplets with daratumumab, carfilzomib, Revlimid and dexamethasone for newly diagnosed multiple myeloma. The study was published two years ago by Ola Landgren [inaudible 00:00:21] Oncology as a clinical trial. This study is the correlative based on the genomics, so we sequence for genome sequencing of all the available samples. The main result is that we discover several known and new genomic features associated with poor or worse outcome and failure to achieve sustainable negativity. These features tend to cocoon together.
So what we identify is a complex network that require more cases to be really deciphered. But that's an important step because it highlights how the technology we use that is whole genome sequencing is probably the way to go to re-understand the DNA based mechanism of resistance for multiple myeloma. But the next steps are in expanding the sample size, working with the community with additional trials where the quadruplets combination with daratumumab plus bortezomib inhibitor plus immunomodulatory agent and corticosteroids were used for newly diagnosed multiple myeloma patients. Try to see also if the same mechanism are involved in a relapse settings because patients get also these drugs in a relapse setting where the disease transform or evolve after previous therapy. And using all this information, once we have a large number of cases, we can of course develop prediction to identify patients that can benefit and patients where they cannot benefit from these regimens. And so for the one that don't, we can identify alternative strategies.
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
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).
The ASCO Post Staff
Eva Hoster, PhD, of Munich University, discusses results from the European MCL Elderly Trial, which confirmed the strong efficacy of rituximab maintenance in minimal residual disease (MRD)-negative patients with mantle cell lymphoma (MCL) after induction. Omitting maintenance based on MRD-negativity is thus discouraged. Considering the short time to progression, more effective treatment strategies should be explored in MRD-positive patients to improve long-term prognosis (Abstract 544).
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).
The ASCO Post Staff
Jiye Liu, PhD, of Dana-Farber Cancer Institute, discusses study findings that demonstrate KDM6A regulates CD38 and CD48 expression in multiple myeloma. Dr. Liu’s team validated combination treatment with an FDA-approved EZH2 inhibitor plus daratumumab, which can overcome daratumumab resistance in preclinical multiple myeloma models, providing the rationale for combination clinical trials to improve patient outcome (Abstract 148).
