637. Myelodysplastic Syndromes—Clinical Studies: Treatment of Higher Risk Myelodysplastic syndromes

Watch Session

Mikkael A. Sekeres, Justin M. Watts, Atanas Radinoff, et al.

Authors Conclusion from the Abstract: In pts with higher-risk MDS, P+A led to longer EFS and a higher CR rate compared with A; the effect on EFS was particularly evident in pts with IPSS-R high- and very-high-risk disease. This finding was associated with longer duration of response, later transformation to AML, increased rate of transfusion-independence and lower transfusion rates with P+A vs A. AEs, SAEs, and grade ≥3 AEs per A cycle dosed appeared lower with P+A vs A. Clinical activity was observed in pts with a variety of adverse-risk mutations, and a prognostic risk model that incorporates both clinical and genetic risk factors revealed potential clinical benefit among pts with high-risk MDS. Further evaluation of P+A vs A is ongoing in a randomized phase 3 trial (NCT03268954).

Raphael Itzykson, Valeria Santini, Cendrine Chaffaut, et al.

Authors Conclusion from the Abstract: RCTs are feasible in advanced proliferative CMML, which remains an unmet medical need. In these pts, DAC did not provide an overall or event-free survival advantage over HY. HY remains a valid option in advanced proliferative CMML. However, one third of HY pts subsequently received an HMA and more DAC pts achieved a response and were bridged to HSCT.

Nathan Radakovich, David A. Sallman, Rena J. Buckstein, et al.

Authors Conclusion from the Abstract: We developed and externally validated a personalized prediction model that uses changes in blood counts during the initial 3 cycles of HMA therapy and can predict response or resistance to treatment with high accuracy. The model can provide personalized explanations of the variables that inform a given outcome. It can be used to develop novel clinical trial designs in which pts who are predicted not to respond within 3 cycles of HMA therapy can receive an investigational agent in addition to continuing HMA or change treatment entirely, whereas patients who are predicted to respond continue to receive HMA monotherapy.

Jacqueline S. Garcia, Andrew H. Wei, Uma Borate, et al.

Authors Conclusion from the Abstract: The combination of Ven+Aza demonstrates promising efficacy, including response durability, and an acceptable safety profile for patients with HR-MDS. Maintenance in physical functioning and clinically meaningful improvement in dyspnea and fatigue were observed throughout the first 48 weeks, although these data are not yet mature and low patient numbers beyond Cycle 7 limit conclusions. Additional follow-up data and correlation with disease risk features including mutations will be presented at the meeting.

Andrew M. Brunner, Jordi Esteve, Kimmo Porkka, et al.

Authors Conclusion from the Abstract: Sabatolimab + HMA is well tolerated in pts with AML and HR-MDS and continues to show promising antileukemic activity and emerging durability. These results support TIM-3 as a potential therapeutic target and provide a basis for further development of sabatolimab + HMA in pts with AML or higher-risk MDS.

Uwe Platzbecker, Pierre Fenaux, David P. Steensma, et al.

Authors Conclusion from the Abstract: Imetelstat achieved an 8-w TI rate of 42% for a median duration of 20 mo, the longest so far reported with any agent in non-del 5q LR-MDS, and 29% of pts achieved TI ≥ 1 y. Furthermore, a high and durable HI-E rate (68% for median of 21 mo) was also achieved in this population of heavily RBC TD, ESA-R/R LR-MDS. Enrollment is ongoing in the Phase 3 portion of IMerge, a placebo-controlled trial of the efficacy and safety of imetelstat, including potential predictive biomarkers of response.