Multiple Myeloma Coverage from Every Angle

Biomarker May Predict Ultra High–Risk Genetic Features of Myeloma

By: Julia Fiederlein
Posted: Monday, August 10, 2020

According to a recent study, published in Leukemia, the presence of SKY92 tumor signatures and certain high-risk chromosomal aberrations may be predictive of ultra-high-risk multiple myeloma. Martin F. Kaiser, MD, of The Institute of Cancer Research (ICR), London, and colleagues proposed that patients with such genetic features may benefit from intensified ongoing therapy with combination agents, rather than lenalidomide therapy.

“Testing for high-risk genetic features could help target myeloma treatment, focusing on the specific needs of each patient,” Dr. Kaiser commented in an ICR press release. “The next step is to combine our results for this study with the ongoing OPTIMUM trial, which will provide us with more information on how to tailor treatment for patients at ultra-high risk based on genetic information.”

The investigators examined the outcomes for patients with SKY92 signatures and/or chromosomal high-risk markers, such as t(4;14), t(14;16), t(14;20), gain(1q), and del(17p). A double-hit tumor was defined as the co-occurrence of at least two of these chromosomal high-risk markers. Samples from 329 patients with newly diagnosed multiple myeloma who received intensive therapy while enrolled in the phase III Cancer Research UK Myeloma XI trial were analyzed by quantitative reverse transcriptase–polymerase chain reaction and microarray.

The patients were classified into a double-hit and SKY92 group (9.7%), a double-hit or SKY92 group (23.4%), a single chromosomal high-risk marker group (24.0%), or a no-risk marker group (42.9%) based on their genetic features. Hazard ratios for overall survival compared with those without risk markers were 11.0, 3.8, and 1.9, respectively. Patients with SKY92 and/or double-hit tumors did not appear to benefit from lenalidomide single-agent maintenance, whereas patients with a single chromosomal high-risk marker or no-risk markers experienced extended progression-free survival. All of the patients in the double-hit and SKY92 group experienced disease progression, with a predicted overall survival of 12.5% at 48 months.

Disclosure: For full disclosures of the study authors, visit

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