Held in Tel Aviv, Israel, the 2020 MDS Foundation meeting gave key updates on novel drug combinations, the impact of the inflammasome & the tumor microenvironment as well as how we can further harness epigenetics. See our top pics below!
Chair and meeting organizer, Moshe Mittelman, MD, Tel Aviv University, Israel, discusses the structure of the 2nd Regional Symposium on Myelodysplastic Syndromes (MDS 2020). Compared to other hematological malignancies, MDS research had until recently yielded fewer innovations. Prof. Mittelman highlights the encouraging progress currently being made in the etiology, pathogenesis, and treatment of MDS.
Luspatercept for MDS-associated anemia
The ineffective erythropoiesis characteristic of MDS can render patients anemic and hence dependant on transfusion. While erythropoiesis-stimulating agents (ESAs) can be helpful, many remain transfusion-dependant. Luspatercept is a recombinant fusion protein that targets the TGF-β signaling pathway to reduce SMAD2 and SMAD3 signaling. Researchers have investigated the use of luspatercept for the treatment of anemia in patients with lower-risk MDS with ring sideroblasts. The MEDALIST study (NCT02631070) found that transfusion independence for 8 weeks or more was observed in a higher proportion of patients treated with luspatercept compared with placebo (38% vs. 13% [P<0.001]).1 In this interview Alan List, MD, Tampa, FL, discusses the use of luspatercept for MDS-associated anemia.
A hidden treasure trove? MicroRNA signatures in MDS
Micro Messenger Ribonucleic Acids (microRNAs) are short, non-coding RNA molecules that not only contribute to the pathogenesis of MDS, but also act as epigenetic regulators and potentially hold very valuable prognostic information for the early diagnosis and classification of the disease.2
In this interview, Inga Mandac, MD, Clinical Hospital Merkur, Zagreb, Croatia, discusses the valuable work being conducted in Croatia on the use of microRNAs.
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As previously mentioned, ESAs can be useful in the treatment of MDS-associated anemia. ESAs can be combined with granulocyte colony-stimulating factor (G-CSF) to bolster efficacy. However, research – specifically randomized trials – in this field is limited. A systematic review highlighted that erythroid response rates increased with the addition of G-CSF in two randomized trials (33% and 40% after low-/standard-doses of ESA alone vs. 65% and 73% after combination treatment).3 In this interview Nicolas Bonadies, MD, Bern University Hospital, Bern, Switzerland, discusses the efficacy of combining G-CSF with erythropoietin EPO for low-risk MDS patients, highlighting the lack of research investigating G-CSF with high-dose EPO.
Lenalidomide, mutations & MDS outcomes
Chromosomal abnormalities play a huge role in the prognosis of MDS. Patients with a single del(5q31) have favorable outcomes that deteriorate with further mutations. It has been reported that lenalidomide can bring about hematological and cytogenetic remissions when used for the treatment of patients with isolated del(5q31) mutations and those with one additional abnormality.4 In this interview, Valeria Santini, MD, University of Florence, Florence, Italy, outlines the heterogeneity seen in patients treated with lenalidomide and how patient stratification can be used to improve overall outcomes. Dr Santini goes on to discuss the benefit of using immunosuppressive treatment for younger patients with MDS that have a hyperplastic marrow and are also receiving anti-thymocyte globulin (ATG) +/- cyclosporine.
Pevonedistat with azacitidine for high-risk MDS
Pevonedistat is a first-in-class NEDD8-activating enzyme inhibitor that downregulates Cullin ring ligases (CRL), interfering with the shuttling and degradation of proteins in the proteasome, leading to the accumulation of CRL substrates.5
In this interview, Moshe Mittelman, MD, Tel Aviv Sourasky Medical Center, Israel, discusses the use of pevonedistat in the treatment of patients with MDS in addition to azacitidine. Prof. Mittelman goes on to discuss the promising research currently underway in the use of this therapy.
Written by Thomas Southgate
Fenaux P, Platzbecker, Ghulam M et al. Luspatercept in Patients with Lower-Risk Myelodysplastic Syndromes. NEJM. 2020 Jan;382:140-151.
Paro M, Mandac I, Kaić G et al. Expression of miRNA (miRNA) in myelodysplastic syndrome (MDS). Medicinski vjesnik. 2019;141(1);7-8.
AffentrangerL, Bohlius J,Hallal M et al. Efficacy of granulocyte colony stimulating factor in combination with erythropoiesis stimulating agents for treatment of anemia in patients with lower risk myelodysplastic syndromes: A systematic review. Critical Reviews in Oncology/Hematology. 2019 April;136;37-47.
Giagounidis A, Germing U, Strupp C et al. Prognosis of patients with del(5q) MDS and complex karyotype and the possible role of lenalidomide in this patient subgroup. Annals of Hematology. 2005:84;569-571.
Moyo T, Watts J, Skikne B et al. Preliminary Results from a Phase II Study of the Combination of Pevonedistat and Azacitidine in the Treatment of MDS and MDS/MPN after Failure of DNA Methyltransferase Inhibition. Blood. 2019 Nov:134(1).
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