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I. Misiewicz-Krzeminska et al.
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These results are consistent with the longer survival dis- played by relapsed/refractory MM patients treated with lenalidomide who expressed high levels of IKZF1/3 pro- tein, as evaluated by immunohistochemical staining.46
Although the number of patients analyzed in this study is relatively small, the survival analysis carried out dividing patients according to drug therapy showed that high levels of Cereblon and Ikaros proteins are associat- ed with a longer PFS only in patients who receive immunomodulatory drugs and not in those who are treated with other drugs. Other studies reached the same conclusion that the level of Cereblon can predict the out- come of patients with MM mainly in those treated with immunomodulatory drugs.47–50 By contrast, in the present series of MM patients, the level of Aiolos did not influ- ence the outcome of the patients treated with immunomodulatory drugs.
In summary, we present the implementation of a novel technique based on capillary nano-immunoassay for quantifying protein expression in MM samples in the clin- ical setting. The requirement for only a relatively small
Figure 6. Progression-free sur- vival in patients with low and high Cereblon, Aiolos and Ikaros protein levels, depend- ing on the treatment scheme (only patients treated accord- ing to GEM2010 trial received lenalidomide). The log-rank test was performed for each protein and Kaplan-Meier curves represent progression- free survival of MM patients depending on protein status. Cutoff Finder software (http://molpath.charite.de/cut off) was used to obtain the optimal cutoff, which was defined as that producing the most significant split that dis- criminates between good and poor survival by examining all the possible cutoffs using the log-rank test.
amount of material means that, for the first time, more than 20 proteins can be analyzed using the same sample frozen for DNA and RNA analysis. This makes the CNIA platform a fast, effective and accurate tool for exploring the impact of different proteins on the survival of patients with MM and for investigating new protein biomarkers that could help to predict the response to new drugs that directly target specific proteins. These encouraging results require further validation in a larger cohort of patients with MM or other hematologic malignancies.
Acknowledgments
The authors thank Isabel Isidro, Teresa Prieto and Vanesa Gutierrez for their technical assistance.
Funding
This work was funded by a grant from the International Myeloma Foundation's Black Swan Research Initiative® and “Gerencia Regional de Salud, Junta de Castilla y León” (BIO/SA35/14). WESTM platform was acquired thanks to INNOCAMPUS Program (CEI10-1-0010).
haematologica | 2018; 103(5)