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Advancing Understanding of the Efficacy of Immunomodulatory Drugs in Myeloma

By: Celeste L. Dixon
Posted: Wednesday, February 27, 2019

Conflicting results of previous studies were the impetus for Katharina Kriegsmann, MD, MBA, of Heidelberg University, Germany, and colleagues to examine a population of 214 patients with newly diagnosed multiple myeloma to see whether the expression levels of cereblon-binding proteins in multiple myeloma cells could be assessed feasibly, on a large scale, by flow cytometry. The team found that they could be, which will likely have future clinical significance.

Immunomodulatory drugs such as lenalidomide are effective in the treatment of multiple myeloma, in part because, as has been shown in vitro, they degrade cereblon-binding proteins. However, as the team described in the Blood Cancer Journal, the results of previous studies varied regarding the prognostic value for progression-free and overall survival in patients whose multiple myeloma cells expressed two such proteins—IKZF1 and IKZF3—perhaps because those studies were performed using relatively small patient cohorts, Dr. Kreigsmann and colleagues speculated. Their study was reportedly the largest to date, in terms of patient samples analyzed, “to characterize the association between cereblon-binding proteins in multiple myeloma cells and clinical characteristics at first diagnosis,” they continued.

In their analysis, the investigators observed overexpression of cereblon-binding proteins in multiple myeloma cells with gain of chromosomes 5, 9, 11, 15, and 19. “This is consistent with the previously proposed positive regulation of [the] MYC [oncogene] by IKZF1 and IKZF3, as well as MYC activation in hyperdiploid multiple myeloma cells,” they concluded. “The correlation results and subgroup analyses on cereblon-binding protein expression levels and response to lenalidomide-based induction therapy are still pending and will provide more insights into the predictive value of cereblon-binding protein levels for immunomodulatory drug treatment.”

Disclosure: The study authors’ disclosure information may be found at nature.com.



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