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
Abdul Rahman Al Armashi, MD, of Seidman Cancer Center, Case Western University, University Hospitals Cleveland Medical Center, discusses a retrospective analysis, using a CDC database, in one of the largest subgroup-based racial population studies analyzing mortality trends in patients with acute myeloid leukemia (AML). Between 2000 and 2019, AML mortality was the highest in Whites and the lowest in American Indians or Alaska Natives. The highest rate of increase in mortality was seen in Asians or Pacific Islanders. Dr. Al Armashi talks about the many variables that might contribute to these inequalities (Abstract 600).
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
Irene Roberts, MD, of Oxford’s Weatherall Institute of Molecular Medicine, discusses children with Down syndrome, who have a more than 100-fold increased risk of developing acute myeloid leukemia before their fourth birthday compared to children without Down syndrome. Their risk of acute lymphoblastic leukemia is also increased by around 30-fold. Dr. Roberts details current knowledge about the biologic and molecular basis of this relationship between leukemia and Down syndrome, the role of trisomy 21 in leukemogenesis, and the clinical implications of these findings.
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
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).
