He noted that one exception is a subset of approximately 15% to 20% of patients with MM who harbor a specific cytogenetic translocation between chromosomes 11 and 14. These patients have exhibited high odds of responding to the newly approved agent venetoclax. “This may be the first clear situation in MM where the presence of a cytogenetic abnormality will determine therapy,” said Dr Costa.
He further acknowledged there is no doubt that high-risk patients have the greatest need for advances in therapy. However, any drug regimen that benefits patients with high-risk MM would probably also benefit standard-risk patients. According to Dr Costa, a promising trend in the treatment of MM is the emergence of multiple therapeutic approaches involving immunotherapies.
“By engaging the immune system to attack MM cells based on what is common to all or most cases, [compared with] what is distinct to a subset of patients, we are likely to reach progress with a strategy that is somewhat at odds with personalized medicine,” he said. “This is being accomplished with the use of monoclonal antibodies, CAR T cells, and soon antibody drug conjugates and T cell engagers.”
The review authors noted that in order for biomarkers to be effective in driving personalized treatment, they must be robustly and reproducibly measurable. Such validated myeloma biomarkers could help predict patient outcomes and could be used to adopt therapies targeting initiating lesions or lesions with a high cancer clonal fraction. Some potentially predictive targets include IDH1/IDH2 mutations, loss of heterozygosity or ATM/ATR mutations, and FGFR3 mutations. Currently, several agents that target these mutations are being studied in large umbrella studies such as the Multiple Myeloma Research Foundation (MMRF) Myeloma-Developing Regimens Using Genomics (MyDRUG) study (ClinicalTrials.gov Identifier: NCT0372703) and the Canadian Profiling and Targeted Agent Utilization Trial (CAPTUR) study (ClinicalTrials.gov Identifier: NCT03297606).
In the MyDRUG trial, which was launched in November 2018, researchers are investigating targeted treatments for high-risk patients with MM. It is a platform trial, meaning researchers are able to rapidly test actionable agents in patients who might benefit. Additionally, agents that do not show efficacy in targeted patient populations can be removed from the trial and other new, targeted agents can be quickly inserted and tested.
“We have made some strides with tailoring therapy [to individual patients] based on cytogenetics, and the next step is the MyDRUG study that will profile each patient’s specific cancer in order to tailor therapy,” said Mark Schroeder, MD, of the divisions of hematology and oncology at the Washington University School of Medicine in St. Louis, Missouri, in an interview with Hematology Advisor. “This is very exciting and will be followed by immunotherapy tailoring. I think we are just beginning to be able to better personalize therapy, not just based on treatment side effects but also on the specific cancer profile.”
1. Pawlyn C, Davies FE. Towards personalized treatment in multiple myeloma based on molecular characteristics [published online December 26, 2018]. Blood. doi: 10.1182/blood-2018-09-825331