MDS Professional Report

Drs Nikolaos Papadantonakis of Emory, Atlanta, US, and Moshe Mittelman, Tel-Aviv, Israel, discuss trials presented in American Society of Hematology (ASH) 2023 meeting. They provide some data on luspatercept, imetelstat, roxodustat and Ker-050.

Prof. Rena Buckstein from Toronto, and Prof. Moshe Mittelman from Tel-Aviv discuss issues related to RBC transfusions, the hemoglobin threshold for transfusion and related quality of life issues.

Prof. Akiko Shimamura of Harvard Medical School, Boston, a world known expert of pediatric hematology discusses with Prof. Guillermo Sanz ,of Valencia and Prof. Moshe Mittelman, of Tel Aviv, the various aspects of bone marrow failure including childhood MDS, the differences of this medical problem between adults and children, the unique approach to sick kids and the increasing number of promising therapeutic options.

Drs. Rafael Bejar (San Diego) and Moshe Mittelman (Tel Aviv) discuss several papers highlighting the role of genetics in MDS diagnosis, follow up and prediction of treatment. They also discuss the role of the newly approved luspatercept in the treatment of anemic transfusion-dependent patients with lower-risk MDS

Drs. Moshe Mittelman, of The Tel Aviv Sourasky Medical Center, and DroritMerkel, of the Sheba Medical Center, both from Tel Aviv University, Israel,discuss several important presentations from the recent 2021 ASH meeting.They focus on the new IPSS-M classification, discuss the approach to theMDS patient who is currently defined by IPSS/R as belonging to the /lower-risk group but in fact the disease behaves like a higher-risk. Finally, theydiscuss issues regarding the treatment of patients with HR-MDS: What can beadded to hypomethylating agents ? Targeted therapy with IDH1/2 inhibitionand more…

Chien Aza – Pembro - BJHThe combination of azacitidine and pembrolizumab may be a potential effective regimen for patients with higher-risk MDS and may lead to the introduction of an important class of medications into MDS practiceNazha, Prog model – JCOA personalized prediction model, based on clinical and genomic data, outperformed established prognostic models in MDS. The use of digital tools allow us to manage big data taken from large numbers of patients and include them in the newly developed diagnostic and prognostic models. Keundgen , t-MDS- Leukemia Therapy-related MDS should be classified as a separate entity distinct from other WHO-classified t-myeloid neoplasms, which would enhance treatment decisions and facilitate the inclusion of t-MDS patients into clinical studies. Strapatsas, PLT, Ann Hem The authors re-confirm the importance of PLT count as a prognostic factor in MDS, both at presentation and during the disease course. Bleeding is a leading (3rd ) cause of death in these patients.

We will discuss the addition of venetoclax to hypomethylating agents in the treatment of advanced myeloid neoplasms, especially higher-risk myelodysplastic syndromes.We will then report a study testing the efficacy and safety of imetelstat, a new telomerase-inhibitor, in the treatment of patients with lower-risk MDS and anemia following ESA failure.We will then review an interesting therapeutic approach to improve or restore erythroid response by adding lenalidomide to MDS patients treated with erythropoietin but lost the response.Finally, we will return to the "hot" topic of targeting the TP53 mutation, by summarizing an important clinical trial using a TP53 activator.

PAPER 1Authors: Vijenthira A. et al. (Princess Margaret, Toronto)Title: Outcomes of patients with hematologic malignancies and COVID-19: a systematic review and meta-analysis of 3377 patientsDescription:⦁ About a third of hospitalized adult patients with hematologic malignancy and COVID-19 – dye. ⦁ No need to withhold anti-cancer treatment from these patients.Paper 2Authors: P. Fenaux; U. Platzbecker; A. List and colleagues, multicenterTitle: Luspatercept in Patients with Lower-Risk Myelodysplastic SyndromesDescription: Luspatercept, an activin receptor derived agent, improves the anemia in LR-MDS patients. Thus, we have another approved anti-anemic agent in addition to ESAs for these patients.Paper 3Authors: David Henry et al. , multicenter ((Disclosure – I am a co-author)Title: Oral Roxadustat Demonstrates Efficacy in Anemia Secondary to Lower-Risk Myelodysplastic Syndrome Irrespective of Ring Sideroblasts and Baseline Erythropoietin LevelsDescription: Roxadustat, an oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor, is another investigated effective agent for the anemia in LR-MDS.Paper 4Title:  Randomized phase 2 trial of pevonedistat plus azacitidine versus azacitidine for higher-risk MDS/CMML or low-blast AMLAuthors: M.A. Sekeres, and colleagues, multicenter, multunationalDescription:  Pevonedistat, a NEDD8 inhibitor, together with azacitidine, improves the response and prognosis in HR-MDS patients.

Bernard E et al: In the first presented study, Dr. Elza Bernard and colleagues deliver an important lesson about the high-risk mutation TP53. That is: not all of them are infeed associated with poor prognosis.Sallman DA et al:A recent study led by Dr. David Sallman tested the efficacy of the combination azacitidine and eprenetapopt (formerly APR-246), a TP53-Mutant activator, in patients with higher-risk MDS.Goll JB et al:One of the more interesting presentations in the last ASH 2020, was that of Dr. Yohannes Goll and others. They showed that adding molecular analysis they can improve the diagnostic accuracy. Indeed 7 genes significantly reduced pathological misclassification.Platzbecker U et al:A group of international investigators, led by Dr. Uwe Platzbecker, from Leipzig, reported in last ASH (2020) their encouraging experience with imetelstat, a telomerase-inhibitor to improve anemia in lower-risk MDS patients after ESA failure.