Myeloma care should include “state of the art” genetic testing to identify mutations linked to high-risk disease, British researchers have said.
A new study has shown that patients carrying two or more of a list of known genetic abnormalities face significantly poorer prognosis.
According to the study, led by the Institute of Cancer Research, London, patients with two or more of these mutations face a 2.28-fold increase in risk of early disease progression compared with those without. They are also nearly three times as likely to die early from the disease.
Those with a single high risk cytogenetic abnormality (HRCA) faced a 1.69 times increased risk of early death and a 1.51 times increased risk of early disease progression, according to the study.
The findings, reported in the Journal of Clinical Oncology, come from a new analysis of 24 randomised control trials of treatment of the disease, including research from Germany, the Netherlands, Italy and Spain. This gave data on nearly 14,000 patients.
The researchers asked the clinical study teams to analyse their data for a group of known high-risk cytogenetic abnormality (HCRAs) including t(4;14), t(14;16), del(17p), and gain(1q). The results were then combined for a meta-analysis.
The researchers report that the findings proved consistent over time, even among more recent trials.
The research team believes that more tailored approaches are needed for high-risk patients. They point to the recent OPTIMUM MUK 9 trial in the UK when new treatments were tested for high-risk patients. This suggested that five drugs and a stem cell transplant could double survival for high-risk patients. These results have informed good practice guidelines by the British Society for Haematology – but have not yet been adopted by the NHS.
Study leader Professor Martin Kaiser, professor of molecular haematology at the ICR, said: “Our research highlights the critical unmet need in this group of patients who are not benefiting from current standard treatment for 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 myeloma patients 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.”
Fellow researcher Professor David Cairns, from the University of Leeds, added: “This study shows the most convincing evidence yet that multiple genetic abnormalities lead to poor prognosis for all patient groups."
Shelagh McKinlay, director of research at Myeloma UK, backed the call for early access to genetic testing.
She said: “Professor Kaiser’s research 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.
“This work also shows the clear need for greater access to early genetic testing so we can target people’s cancer far more effectively.”
Source:
Kaiser MF, Sonneveld P, Cairns DA, Raab MS, San-Miguel Izquierdo J, Zhang R, Acosta J, Larocca A, Popat R, Li C, Baertsch MA, Brown SR, Lahuerta Palacios J, Gandhi AK, Macé S, Musto P, Yong K, Mai EK, Dubin F, Blade J, Capra A, Cook G, Bertsch U, Mateos MV, Boccadoro M, Jackson GH, Gutiérrez NC, Gay F, Weinhold N. (2025) “Co-Occurrence of Cytogenetic Abnormalities and High-Risk Disease in Newly Diagnosed and Relapsed/Refractory Multiple Myeloma.” Journal of Clinical Oncology, 18 February 2025, doi: 10.1200/JCO-24-01253.
Link: https://ascopubs.org/doi/10.1200/JCO-24-01253
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