Immunoglobulin light-chain amyloidosis shares genetic susceptibility with multiple myeloma

here is performed on a patient specimen after purification and elimination of non-B-cells. Additional work will be required to further characterize the presence and composition of these distinct subpopulations. Priming by Noxa, a specific proapoptotic modulator of antiapoptotic Mcl-1, is not associated with either alvocidib response or TLS, consistent with Mcl-1 not being a driver mechanism. Conceivably, patients could be stratified by cytogenetics and BH3 profiling to increase the overall response rate from 35 to 50% as observed in previous clinical studies. In the current patient set, 23 of the 62 analyzed patients achieved a PR to alvocidib (37.1%.) In our analyses, the combination of Hrk and trisomy 12 yielded an AUC of 0.83. By closer examination of the ROC curves, 95.6% of responder patients were identified (sensitivity) concurrently to discrimination of 66.7% of likely PD/SD patients (specificity). If the predictive value of such an applied biomarker is to triage the likely non-responder patients (here the triaging of 26 PD/SD patients, while also mis-identifying 1 likely PR patient), then the response rate increases from 37.1 to 62.9% (an overall 69.5% improvement of response rate). Similarly, TLS incidence could be decreased from 13% observed in the EFC6663 study to a minimal number moving forward. While larger cohorts will be required to fully define the extent of medical utility for such diagnostics, these early observations may hold promise for alvocidib impact in CLL patient options and improved outcomes.