637. Myelodysplastic Syndromes—Clinical Studies: Personalized Clinical-Decision Tools and treatment of lower risk MDS
Félix López Cadenas, Eva Lumbreras, Blanca Xicoy, et al. and Maria Diez-Campelo
Authors Conclusion from the Abstract: In this interim analysis we confirm that low dose LEN (5 mg) in anemic non-TD low risk MDS del(5q) patients prolongs the period of time to TD (75.7 mo vs 25.9 mo), improves Hb levels (72.5% of ER) and induces clonal responses (70% complete CyR), ie potentially more responses than in historical series of MDS del(5q) treated with LEN at time of TD, with a manageable safety profile, and no increased progression rate. Longer follow up will be required to assess the effect of early treatment with LEN, and particularly the effect of the early reduction of the del(5q) clone size, on long-term outcomes.
Soo Park, Brian M Reilly, Timothy Luger, et al.
Authors Conclusion from the Abstract: DNAm patterns early in the course of HMA treatment correlate with eventual response, with CRs associated with the greatest degree of demethylation. Responders are more likely to have greater demethylation that may reflect greater effective AZA exposure or slower remethylation dynamics. Addition of PEV may intensify site-specific demethylation in responders and increase the proportion of responding patients. With a median TTR of 3-4 months in the P-2001 study, depth of demethylation at the C2D22 timepoint may help predict eventual response. Strategies to augment demethylation with adjunctive agents or HMA dose escalation in patients with early inadequate demethylation should be investigated. Ongoing work will incorporate mutation status and focus on refining DNAm signatures that can predict eventual response.
Constance Baer, Anna Stengel, Wolfgang Kern, Claudia Haferlach, and Torsten Haferlach.
Authors Conclusion from the Abstract: We suggest that molecular genetic markers should be recognized as presumptive evidence of MDS and allow the diagnoses to be based on three cornerstones: morphology, cytogenetics, and molecular genetics. In two-thirds of MDS and one-third of CCUS patients mutations can be identified that allow personalized treatment based on respective molecular genetics even independent of other currently used diagnostic labels.
Lin-Pierre Zhao, Maxime Boy, Celia Azoulay, et al.
Authors Conclusion from the Abstract: Our study provides an extended mutational landscape of MDS/CMML associated with SIAD, and finds a correlation between TET2/IDH mutations, T lymphocyte imbalance and association with SIAD in those diseases. This correlation could suggest common mechanisms underlying both SIAD and MDS/CMML, and reinforces our observations of a frequent positive effect of Azacytidine (a drug with better response in patients with TET2mutation) on both MDS/CMML and SIAD in patients with both disorders (Fraison, Leuk Res 2016). Further analysis of the functional role of T lymphocytes in those patients is underway.
Johannes B Goll, Travis L Jensen, R. Coleman Lindsley, et al.
Authors Conclusion from the Abstract: We identified that VAFs for 7 genes can correctly re-classify subjects as either MDS or Other in 74% of cases that were misclassified between local and central pathology review. Further assessment on an independent cohort showed an accuracy of 83% of the model. Taken together, these data suggest that complementing pathology reviews with targeted sequencing of 7 genes could improve MDS diagnosis.
Nathan Radakovich, Manja Meggendorfer, Luca Malcovati, et al.
Authors Conclusion from the Abstract: We developed and externally validated a highly accurate and interpretable model that can distinguish MDS from other myeloid malignancies using clinical and mutational data from a large international cohort. The model can provide personalized interpretations of its outcome and can aid physicians and hematopathologists in recognizing MDS with high accuracy when encountering pts with pancytopenia and with a suspected diagnosis of MDS.