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).
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.
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).
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).
Tycel J. Phillips, MD, of the City of Hope National Medical Center, discusses data that showed fixed-duration glofitamab monotherapy induced high and durable complete response rates in patients with mantle cell lymphoma (MCL) who received obinutuzumab pretreatment. This is one of the largest data sets and longest follow-ups reported with a CD20/CD3 bispecific monoclonal antibody for patients with relapsed or refractory MCL (Abstract 74).
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).
Kathryn R. Tringale, MD, of Memorial Sloan Kettering Cancer Center, discusses an assessment of 559 patients with primary central nervous system (CNS) lymphoma and the factors associated with consolidation therapy selection, outcomes after consolidation therapy accounting for patient factors, and patterns of disease failure. The initial treatment response was prognostic and predictive of relapse patterns (Abstract 557).