High-risk genetic changes with myeloma tied to poorer outcomes
Specific abnormalities in cancer cells known to cause more aggressive disease
The presence of more than one high-risk genetic abnormality is associated with dramatically more aggressive multiple myeloma, a study reported.
Its findings highlight the importance of testing myeloma patients for these genetic abnormalities, helping to better understand their disease’s potential course and guiding treatment decisions, the researchers wrote.
“The results of this study have enabled us to more accurately classify the aggressiveness of an individual patient’s cancer,” Martin Kaiser, MD, the study’s lead author and a professor of molecular hematology at The Institute of Cancer Research in the U.K., said in an institute news story. “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.”
The study, “Co-Occurrence of Cytogenetic Abnormalities and High-Risk Disease in Newly Diagnosed and Relapsed/Refractory Multiple Myeloma,” was published in the Journal of Clinical Oncology.Â
A number of high-risk cytogenetic abnormalities seen with myeloma
Survival rates for myeloma patients have improved considerably over the past few decades with new treatments, but there’s a lot of variability from person to person in myeloma outcomes. Previous research identified several so-called high-risk cytogenetic abnormalities (HRCAs), which are specific genetic changes in cancer cells that link with more aggressive disease.
Research also has shown that people with myeloma whose cancer carries at least one HRCA have poorer survival odds than patients with no HRCAs. But more than one of these high-risk genetic abnormalities can be present in the same patient — a condition sometimes referred to as double-hit myeloma (or multi-hit, if more than two HRCAs present). It hasn’t been clear, however, whether the odds of survival substantially differ between people with more than one HRCA and those with one alone.
To gain insight, the researchers analyzed data from 24 myeloma clinical trials. These data covered nearly 14,000 patients, from individuals with newly diagnosed myeloma to people with relapsed or refractory myeloma, meaning the disease had failed to respond to treatment or had gotten worse after initially responding to treatment.
“Despite the considerable data available from trials and real-world experience, the association between outcome and co-occurrence of [HRCAs] in different patient groups remains unclear,” the researchers wrote. “Our analysis, which included 24 randomized controlled trials comprising 13,926 patients, addresses this question.”
Survival odds decline substantially with two or more high-risk genetic changes
Results showed that, compared with patients who had no HRCAs, survival odds in patients with one HRCA fell by about 69%. In those with more than one HRCA, the odds of survival were substantially lower — a nearly threefold decrease compared with patients who had no HRCAs.
Data on progression-free survival — that is, the chances of being alive without the cancer getting worse — showed a similar pattern: Odds worsened by 51% in patients with one HRCA, and by more than twofold in patients with two or more HRCAs.
“We show that co-occurrence of two or more [HRCAs] confers significant poor prognosis in patients” with myeloma, the researchers concluded.
These findings were broadly comparable when looking at people with newly diagnosed disease or those with relapsed/refractory myeloma. The effects of HRCAs also were consistent irrespective of what type of myeloma treatment patients were getting.
“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,” Kaiser said.
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