Offering genetic testing to patients with multiple myeloma may help physicians to determine which patients have the most aggressive types of the disease and how to target their malignancy more effectively, according to a recent study published by Kaiser et al in the Journal of Clinical Oncology.
Background
Multiple myeloma is often treated with targeted drugs, chemotherapy, and stem cell transplants. Five or six key high-risk cytogenetic abnormalities are used to classify multiple myeloma as high risk.
“[Multiple] myeloma is a very complex cancer. While current treatments can work very well for many [patients], there are others who do not respond well and may relapse early,” explained lead study author Martin Kaiser, MD, Professor of Molecular Haematology at The Institute of Cancer Research in London and a consultant hematologist at The Royal Marsden National Health Service Foundation Trust.
Although more than 50% of patients with multiple myeloma who receive effective treatment will survive for 5 years or more, between 20% and 25% of patients have specific genetic changes in their cancer cells that make the disease more aggressive and difficult to treat. High-risk patients typically experience disease recurrence much earlier after diagnosis, unless they receive tailored therapy.
“Cancer is not a single disease. There are many different types and subtypes of cancer, each with its own characteristics, risk factors, and causes. Because of this incredible diversity, it is vital that we can diagnose cancer precisely to identify the best treatment for each patient,” detailed Kristian Helin, MSc, PhD, Chief Executive at The Institute of Cancer Research. “This study represents an important step forward in better understanding and defining the needs of [patients with] high-risk multiple myeloma. Every [patient with] cancer should have the opportunity for their cancer to be molecularly profiled to assess biomarkers that can give vital clues about how their disease should best be treated. Biomarker tests can tailor treatment precisely to the patients who will most benefit, which can both improve the lives of patients and increase the cost-effectiveness of treatment,” he revealed.
Study Methods and Results
In this study, investigators conducted a systematic review examining data on high-risk cytogenetic abnormalities in 24 randomized controlled trials of multiple myeloma from across the world spanning 20 years. They then invited the researchers involved in the trials to perform an analysis of their data for both patients with one high-risk cytogenetic abnormality and two or more high-risk cytogenetic abnormalities using a specially designed algorithm. Following the analysis, the researchers sent the individual results of 13,926 patients back, so they could be collated and jointly studied.
The investigators demonstrated that patients who had one high-risk cytogenetic abnormality and those who had two or more high-risk cytogenetic abnormalities had 1.51 and 2.28 times the risk of experiencing early disease progression and 1.69 and 2.94 times the risk of early mortality with standard therapy, respectively, compared with patients who had multiple myeloma without high-risk cytogenetic abnormalities—regardless of the specific type of standard treatment.
Because the project involved many studies over a long period, the investigators noted that the effect remained consistent in trials performed since 2015, reinforcing that some high-risk patients may require more effective, tailored approaches rather than current standard treatment options.
For instance, in the OPTIMUM MUK 9 trial, researchers used the most advanced diagnostics to screen patients for high-risk multiple myeloma and offered these patients personalized treatment. The researchers discovered that an intensive treatment regimen of five drugs along with a stem cell transplant prevented disease progression for three times longer and doubled the survival time in these patients.
Conclusions
“Our research highlights the critical unmet need in this group of patients who are not benefiting from current standard treatment for [multiple] myeloma. We’re aiming to find better ways of treating these patients and improving their outcomes. The results of this study have enabled us to more accurately classify the aggressiveness of an individual patient’s cancer. We would like all [patients with multiple] myeloma to be able to access the newer diagnostic tests, which enable clinicians to group individual patients based on their risk profile and provide treatment that is tailored to their needs,” Dr. Kaiser emphasized. “We have already shown through the OPTIMUM trial that a more personalized approach involving five different existing drugs could help treat patients with the highest-risk [types] of [multiple] myeloma—helping keep them alive and healthy for longer,” he added.
“This study shows the most convincing evidence yet that multiple genetic abnormalities lead to poor prognosis for all patient groups,” indicated co–study author David Cairns, PhD, Professor of Clinical Trials Research and Deputy Director of the Leeds Cancer Research UK Clinical Trials Unit at the University of Leeds. “It was a pleasure to work with academic and industry collaborators from around the world on this federated analysis. The support of Cancer Research UK and Myeloma UK to the Clinical Trials Research Unit at the University of Leeds helped make this project possible,” he continued.
“[The new research] is paving the way for a brighter future for [patients] with [multiple] myeloma. We know that when it comes to treating [patients], a one-size-fits-all approach doesn’t work for [multiple] myeloma. [The new study] takes us a major step forward as we strive to identify patients at high risk of not responding to currently available treatments and to develop bespoke treatments that will keep their cancer at bay for as long as possible,” underscored Shelagh McKinlay, Director of Research and Advocacy at Myeloma UK. “This work also shows the clear need for greater access to early genetic testing, so we can target [patients’] cancer far more effectively. Until we have a cure, it is absolutely vital that [patients with multiple] myeloma are given the best chance to keep their cancer in check, and it starts with making sure they get access to personalized medicine,” she concluded.
Disclosure: The research in this study was funded by Myeloma UK and Cancer Research UK and supported by funding from the National Institute for Health and Care Research and the British Research Council. For full disclosures of the study authors, visit ascopubs.org.
