MDS Hub

In case you missed it: What are the key updates to the classification of MDS in the 5th edition of the @WHO Classification of Haematolymphoid Tumours? Check out our visual abstract summarizing the main changes 👉 loom.ly/8nbWuCY. #MDSsm

Has the IPSS-M model changed the extent of the molecular testing you perform for patients with MDS?

🚨NEWS 🚨 First patient dosed in the phase II BEXMAB trial, evaluating bexmarilimab, an anti-Clever-1 humanized monoclonal antibody, in combination with standard of care in patients with R/R MDS previously treated with HMAs. loom.ly/STJGPwE #MedNews #leusm

Want to find out how the IPSS-R and IPSS-M stratification systems for MDS compare? Find out in our editorial theme article outlining the development of these systems and their pros and cons. 👉 loom.ly/l7pFhKk #MDS #leusm

A big thank you to our funders, who make it possible for us to deliver the MDS Hub Bristol Myers Squibb ThermoFisher Scientific Astex All content is developed independently by SES in collaboration with an expert steering committee; funders are allowed no direct influence on the content of the hub.

🎬 Discover the latest insights on MDS classification systems! Join Pierre Fenaux as he delves into his updated approach in our new video. Don't miss this pivotal discussion from our MDS Hub Steering Committee meeting. 👉 loom.ly/Setfq8s #MDS #MedicalScience

📺 Dive into expert insights on managing lower-risk MDS with signs of erythropoiesis-stimulating agent failure in our latest steering committee meeting video. Join Theo de Witte as he shares treatment strategies. A must-watch! 👉 loom.ly/srZrpcQ #MDSsm

How can clinical trial design in myelodysplastic syndromes be improved with clinically meaningful endpoints? 🔎 Read our latest article to find out! 👇 loom.ly/n5NoVvs #MDS #MDSsm

CONGRESS | #ASH23 Uwe Platzbecker @UwePlatzbecker @UniLeipzig presents from IMerge ph3 trial of imetelstat vs placebo in patients with non-del(5q) LR-#MDS R/R or ineligible for ESAs. ▪️Of 33 patients who achieved ≥24-wk RBC-TI with imetelstat, 63.6% maintained for ≥1-yr; majority had normal karyotype (57%), prior ESA treatment (90%) and were RS+ (71%) ▪️Median duration of RBC-TI in 1-yr TI responders (imetelstat arm) =123 wks, with Hb increase during the longest TI interval = 5.2g/dL ▪️No patients progressed to AML ▪️Of the 21 imetelstat-treated ≥1-yr TI responders, 7 had cytogentic abnormality at baseline, and 4 had a complete cytogenetic response ▪️Gr3-4 thrombocytopenia (67%) and neutropenia (95%) were common AEs in ≥1-yr TI responders @ASH_hematology #MDSsm #leusm

CONGRESS | #ASH23 Enrico Attardi @enrico_attardi @unitorvergata @StJude dissects ICC “diagnostic qualifiers”, using a cohort of 155 patients with #AML progressing from #MDS or MDS/MPN (sAML) and 65 patients with tAML, and comparing to 233 patients with de novo MDS-related AML (AML-TP53, AML with MDS-related gene mutations or cytogenetic abnormalities AML-TP53). ▪️91.7% of sAML cases were AML-MR by 2022 WHO, however ~80% fell into the ICC MDS-related profile with 11.1% not defined ▪️ELN 2022 stratified patients with tAML, but not sAML ▪️Estimated that 70% of sAML and >75% tAML could be captured through RT-PCR and conventional cytogenetics ▪️Proposes that tAML should be classified as a “second” neoplasm rather than sAML, and treatment decisions should be guided by genetic profile rather than antecedent diagnosis of MDS @ASH_hematology #AMLsm #leusm

CONGRESS | #ASH23 @Santin13Valeria @UNI_FIRENZE Imetelstat was superior to placebo in inducing ≥8wk & ≥24 week RBC-TI, regardless of number of baseline mutations ▪️Improved RBC-TI response to imetelstat vs placebo particularly noted in patients with SF3B1 mutations (≥8wk RBC-TI 48.8% vs 16.3, p=0.001) ▪️Patients carrying spliceosome mutations had significantly improved response to imetelstat than placebo (≥8-wk RBC-TI 43.8% vs 14.9%, p=0.001) ▪️Trend towards higher RBC-TI response rate with imetelstat vs placebo in patients with poor-prognosis genes (ASXL1, TP53, ETV6, RUNX1, EZH2): 8 weeks, 31.6% vs 9%; 24 weeks, 9.1% vs 0%) @ASH_hematology #MDS #MDSsm #leusm

CONGRESS | #ASH23 Esther Natalie Oliva @GOM_rc presents an analysis of patient-reported outcomes in patients in the COMMANDS trial. ▪️Good side effect tolerability in both luspatercept and epoetin alfa arms (FACT-An item GP5) ▪️Improved times to sustained improvement to 24 weeks in luspatercept vs epoetin alfa arm for 8 EORTC QLQ-c30 domains, including role functioning (p=0.034), cognitive functioning (p=0.002) and pain (p=0.005), dyspnea (p=0.035), insomnia (p=0.045), appetite loss (p=0.001), constipation (p=0.001), and financial difficulties (p=0.006) ▪️FACT-An time to sustained improvement was similar between arms @ASH_hematology #MDS #MDSsm #leusm

CONGRESS | #ASH23 Valeria Santini @Santin13Valeria @UNI_FIRENZE presents long-term 26 month follow-up of patients with LR #MDS intolerant/ineligible for ESAs in the MEDALIST trial. ▪️Uninterrupted RBC-TI ≥1 yr was achieved by 41.3% of patients who achieved RBC-TI ≥8 wks, and 64.6% who achieved RBC-TI ≥16 wks ▪️Long-term safety was consistent with short-term, with TEAES similar between luspatercept and placebo arms when exposure-adjusted; fatigue rates decreased with increased luspatercept dose and increased Hb levels @ASH_hematology #MDSsm #leusm

CONGRESS | #ASH23 Rami Komrokji @Ramikomrokji @MoffittNews presents a mutational burden analysis from the COMMANDS trial. ▪️Luspatercept showed broad activity across MDS-associated mutations, including difficult-to-treat ASXL1 ▪️Response rates increased with luspatercept vs epoetin alfa in patients with 1–3 mutations overall and in RS+ subgroup; in RS- subgroup, luspatercept and epoetin alfa similar despite mutational burden differences ▪️Patients who were RS- in the epoetin alfa arm had lower mutational burden at baseline compared to RS+ (p=000024) ▪️Benefit of luspatercept seen across IPSS-M risk levels @ASH_hematology #MDS #MDSsm #leusm

CONGRESS | #ASH23 Eshana Shah @YaleMed presents a mixed methods approach to understanding individual-level social determinants of health (SDOH) in 52 patients with #AML, HR #MDS or #ALL, and explains that age (>65yrs), financial toxicity and lower health literacy, but not PHQ-4, contribute to missed clinic visits, and more ER and ICU visits. To address this, SDOH tools are needed to identify vulnerable patients, alongside provision of tailored education, improved caregiver engagement and community partnerships. @ASH_hematology #AMLsm #leusm #leukemia #MDSsm #ALLsm

Elisabetta Sauta @ILeukemia summarizes the significant contribution of transcriptomic features (40%), plus somatic gene mutations and cytogenetic lesions (24%), demographics (20%) and clinical features (15%) to survival prediction, in an integrative analysis of 389 patients with #MDS. By comparing to IPSS-M, she demonstrates enhanced clinical outcome prediction. @genomed4all @SYNTHEMA_EU @ASH_hematology #mdssm

CONGRESS | #ASH23 Caspian Oliai @UCLAJCCC @UCLAHealth discusses ph1b trial of Orca-T. 1-yr RFS was similar between patients aged 18-55yrs (n=38) and those >55 yrs old (n=25); 1-yr NRM=0% in both groups; 1-yr OS=100% and 96%. Donor chimerism at 3mo >90% in all ages. 1 case of ≥Gr3 aGvHD in an older patient. Summarizes that Orca-T is a well-tolerated alternative to conventional transplant and could improve outcomes in older patients. @ASH_hematology #AML #AMLsm #leusm #leukemia

CONGRESS #ASH23 | Moshe Mittelman presented results from MATTERHORN, an ongoing, double-blind, Phase III trial of roxadustat for treatment of anemia in pts with low-risk #MDS. At week 28 more pts in the roxadustat arm compared with the placebo arm were TI responders (47.5% vs. 33.3%), but this was not statistically significant. However, roxadustat was well-tolerated. #MDSsm

CONGRESS #ASH23 | Rami S. Komrokji discussed results from the Imerge phase III study evaluating the efficacy of imetelstat across different IPSS risk categories. The TI rate for all IPSS risk groups at ≥1-year were 12.5% vs 2.6% for imetelstat vs placebo in the low risk pts and 15.8% vs 0% in intermediate risk pts. #MDS #MDSsm

CONGRESS #ASH23 | Guillermo Garcia-Manero presented results from the phase III COMMANDS trial of Luspatercept Versus Epoetin Alfa in ESA-Naive pts with low-risk #MDS. 2.7% and 3.3% of pts in the luspatercept and epoetin alfa arms, respectively, progressed to #AML. With luspatercept, RBC-TI duration and erythroid responses were superior compared with epoetin alfa. #MDSsm

What is the long-term benefit of luspatercept in the treatment of anemia for transfusion-dependent patients with ring sideroblast-positive, lower-risk myelodysplastic syndromes who are erythropoietin-stimulating agent refractory/intolerant? Read our summary of a long-term analysis from the phase III MEDALIST trial 👇 loom.ly/fzX5stA #MDS #leusm