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With an increased number of therapeutic options available for Multiple Myeloma (MM) patients, clinicians are faced with the difficult task of choosing which will be the most effective for a given patient. Immunomodulatory drugs (IMiDs) are routinely used for MM treatment and form the backbone of several regimens. In order to establish criteria for the use of IMiDs, in terms of identifying patients that will be either sensitive or resistant, a study was conducted to develop and identify a gene-expression profile (GEP) signature for patient response to IMiD therapy. This retrospective study, conducted by Manisha Bhutani from The Carolinas HealthCare System, Charlotte, NC, USA, and colleagues, and published in the September edition of The Lancet Haematology, used a cohort of patients with either newly diagnosed Multiple Myeloma (NDMM) or relapsed and refractory MM (RRMM), who had been treated in clinical trials with IMiD-containing regimens, and for whom GEP data was publically available.
Data is given as IMiD-14 high group vs IMiD-14 low group:
Using data GEP-data from patients treated with IMiD-based regimens, the IMiD-14 model was developed and extensively validated. This now provides a valuable tool for risk stratification in order to identify patients that will be best suited to IMiD-based regimens or to follow patients during treatment. A high IMiD-14 score will indicate poor PFS and OS, compared with patients with low IMiD-14 scores that have a more favourable prognosis. A question mark over the study is whether it is truly predictive of an IMiD-related response, as patients evaluated received other drugs in their treatments, such as dexamethasone, doxorubicin and high-dose melphalan. The next step will be a functional validation of these gene changes in order to better understand the factors leading to IMiD response versus resistance.
In a Comment by Sinto Sebastian, from the Division of Hematology and Oncology, Mayo Clinic, Scottsdale, Arizona, USA, and also published in The Lancet Haematology, the benefits of such a gene profiling signature were discussed. He proposed that future tests might combine cereblon, Ikaros and Aiolos immunohistochemistry with IMiD-14 gene expression to improve predictive accuracy, as well as future studies to dissect the biological significance of the observed changes.
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