Prognostic Model Developed for Predicting Response to IMiDs in Multiple Myeloma

10/19/17

Researchers developed a novel gene signature that has prognostic value in patients with multiple myeloma who are treated with immunomodulatory derivatives (IMiDs), according to research published in The Lancet Hematology (September 2017;4[9]:e443-e451).

IMiDs are considered one of the critical components of standard-of-care treatment regimens for multiple myeloma. However, survival outcomes achieved with these drugs seem to vary greatly from patient to patient.

Manisha Bhutani, MD, department of hematologic oncology and blood disorders, Levine Cancer Institute (Charlotte, NC), and colleagues sought to develop a gene signature that could better identify whose patients who would gain the most benefit from treatment with IMiDs. The retrospective study included patients with newly diagnosed or relapsed/refractory multiple myeloma treated in clinical trials with IMiD-containing regimens.

A total of 176 IMiD response genes were identified that were differentially expressed before and after patient exposure to these drugs. Among these genes, 14 had significant P values for their association with progression-free survival (PFS) in patients treated in clinical trials. A continuous IMiD-14 score was created – with patients demonstrating a high score considered to be IMiD-resistant.

A training cohort assessed patients with various IMiD-14 scores. Those with high scores had significantly shorter PFS (52%) compared with those with low scores (85%).

Researchers subsequently formed a validation cohort from four studies of IMiD regimens: TT3a, TT3b, TT6, and VAD. Results of the training cohort were further validated in these cohorts (TT3a, 63% vs 87%, respectively; TT3b, 62% vs 80%; TT6, 39% vs 74%; and VAD, 16% vs 54%).

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Researchers also reported that the IMiD-14 model outperformed other previously-developed individual IMiD-resistance biomarkers in predicting survival outcomes.

“Unlike traditional multiple myeloma gene signatures, which predict the overall effect of a certain combination therapy, drug-specific gene signatures derived from pharmacogenomics studies, such as the IMiD-14…are useful complementary tools in the era of personalized medicine,” researchers wrote.

The IMiD-14 model needs to be further evaluated in prospective studies.—Zachary Bessette