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
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
Jennifer R. Brown, MD, PhD, of Dana-Farber Cancer Institute, discusses phase III findings of the ALPINE study, which showed that zanubrutinib is more efficacious and better tolerated than ibrutinib as a treatment for patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). In this first head-to-head comparison of the two BTK inhibitors, the superior progression-free survival of zanubrutinib was observed across all major subgroups, including high-risk patients (Abstract LBA-6).
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
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).
The ASCO Post Staff
Jia Ruan, MD, PhD, of Meyer Cancer Center, Weill Cornell Medicine, and NewYork-Presbyterian Hospital, discusses trial results demonstrating that the triple chemotherapy-free combination of acalabrutinib, lenalidomide, and rituximab is well tolerated, highly effective, and produces high rates of minimal residual disease (MRD)-negative complete response as an initial treatment for patients with mantle cell lymphoma, including those with TP53 mutations. Real-time MRD analysis may enable treatment de-escalation during maintenance to minimize toxicity, which warrants further evaluation. An expansion cohort of acalabrutinib/lenalidomide/obinutuzumab is being launched (Abstract 73).
