Myelodysplastic Syndromes—Clinical Studies: Prognosis and Prediction

793  A Personalized Prediction Model to Risk Stratify Patients with Myelodysplastic Syndromes

Aziz Nazha, et al.

The Abstract concludes: We built a personalized prediction model based on clinical and genomic data that outperformed IPSS and IPSS-R in predicting OS and AML transformation. The new model gives survival probabilities at different time points that are unique for a given pt. Incorporating clinical and mutational data outperformed a mutations only model even when cytogenetics and age were added.

794  From Mild Cytopenia to Overt MDS and AML, the Mutational Profile Predicts Progression, but Not Survival

Jakob Werner Hansen, et al.

The Abstract concludes: We here show that mutational profiling can identify patients with idiopathic cytopenia who are at risk of progression, but in contrast to low-risk MDS, the presence of adverse mutations in patients with idiopathic cytopenia do not predict inferior survival.

795  Combined Impact of Aberrant Immunophenotypes, Somatic Mutations and Cytogenetic Aberrations on the Probability of Developing Myelodysplasia in Patients with Cytopenias of Undetermined Significance

Wolfgang Kern, et al.

The Abstract concludes: In the absence of cytomorphologic signs of dysplasia, findings commonly present in MDS patients, i.e. aberrant immunophenotypes, somatic mutations and cytogenetic aberrations, occur in patients with cytopenias of undetermined significance. The presence of two of these three findings may be considered as a pre-diagnostic state of MDS. Further studies should clarify the diagnostic potential of this approach.

796  Telomere Length and Telomerase Complex Mutations Predict Fatal Treatment Toxicity after Stem Cell Transplantation in Patients with Myelodysplastic Syndrome

Mikko Myllymaki, et al.

The Abstract concludes: Recipient telomere length is independently associated with overall survival after allogeneic HSCT for MDS. Patients age 40 or older with shorter blood cell telomere length have a significantly elevated risk of early NRM with myeloablative conditioning regimens. Clinically unrecognized germline mutations in the telomerase genes TERT, TERC, and DKC1 define a distinct subset of adult patients with sporadic MDS and short telomeres who have poor transplant outcomes. Together, these results indicate that short telomere length in MDS patients mediates fatal treatment toxicity that may be attenuated by lower intensity conditioning approaches.

797  Clinical and Molecular Characteristics of DDX41-Mutated Patients in a Large Cohort of Sporadic MDS/AML

Marie Sebert, et al.

The Abstract concludes: DDX41 germline variant carriers represent a significant part of MDS/AML pts, the vast majority presenting without familial history. The predicted change in protein and/or the presence of a second somatic mutation strongly support the causality of the germline variant in most pts. By contrast with previous reports, pts frequently presented a phase of cytopenia before overt malignancy. Finally, outcome regarding response to treatment and OS in this DDX41-mutated cohort appeared relatively favorable.

798  A Clinical Study of Tomaralimab (OPN-305), a Toll-like Receptor 2 (TLR-2) Antibody, in Heavily Pre-Treated Transfusion Dependent Patients with Lower Risk Myelodysplastic Syndromes (MDS) That Have Received and Failed on Prior Hypomethylating Agent (HMA) Therapy

Guillermo Garcia-Manero, et al.

The Abstract concludes: Early data suggest that Tomaralimab therapy presents a novel and safe treatment for heavily pre-treated low risk/Int-1 MDS HMA-F pts. Tomaralimab exhibited a 50% ORR in heavily pre-treated, transfusion dependent HMA-F patents. Treatment was well tolerated and penetrated the bone marrow. RO in the blood could also be used as a surrogate for RO in the bone marrow. Surprisingly, there was no correlation between efficacy and cytokine concentration in the plasma, although cytokine changes in the bone marrow were not determined. There were however non-significant alterations in TLR2 and related genes in purified bone marrow cells from pts. Studies using these cells are underway to further elucidate the mechanism of action. In brief, Tomaralimab therapy presents a potential therapeutic option for heavily pre-treated low risk pts that have failed HMA therapy.