2) This program is intended for #HCPs & is supported by an independent educational grant from Bristol Myers Squibb. Faculty disclosures & statement of accreditation at https://t.co/8oShcATovC. Earn 0.75hr 🆓 CE/#CME when u follow this 🧵!#FOAMed #MedTwitter #OncTwitter #ONCsm pic.twitter.com/3obwIZEB4h
— @onc_ce (@onc_ce) December 20, 2023
4) Two-thirds of the patients with #MDS present with low-risk (LR) -disease. #Anemia is by far the most common cytopenia in #LR_MDS (present in almost 90% of cases). pic.twitter.com/WtZlICMzLW
— @onc_ce (@onc_ce) December 20, 2023
6) For decades, the therapeutic armamentarium for patients with LR-#MDS was limited to supportive care via blood #transfusions, erythropoietin stimulating agents (#ESAs) and few other agents (#lenalidomide, #hypomethylating agents), and more recently #luspatercept.
— @onc_ce (@onc_ce) December 20, 2023
8a) An important sub-entity of LR-MDS group is ‘#MDS with #SF3B1 mutation’ that majorly overlaps with prior ‘MDS with ringed #sideroblasts (RS)’.
— @onc_ce (@onc_ce) December 20, 2023
9) Moving on . . . pic.twitter.com/351cfjs3fQ
— @onc_ce (@onc_ce) December 20, 2023
11) Recombinant fusion protein #luspatercept acts on TGF beta pathway reduces SMAD2/3 signaling, restoring erythroid maturation (check out this excellent review by @Amitvermamds et al. – 🔓 https://t.co/TCZEzoHJhG). pic.twitter.com/9MOxBm35Ir
— @onc_ce (@onc_ce) December 20, 2023
13) Since approval, clinical studies have been looking into efficacy of #luspatercept as single agent in 1L setting as well as in combinations. At #ASCO23, the #COMMANDS study was presented & interim efficacy analysis of frontline luspatercept vs #ESA was reported.
— @onc_ce (@onc_ce) December 20, 2023
15a) BTW–Imp't for control arm of any study: Dose escalation/modification was done in a fair manner in both arms of #COMMANDS #ASHKudos. This issue has been well described by @Timothee_MD et al ➡️ 55% of clinical trials favored the experimental arm (https://t.co/8jAzMbDxR4).
— @onc_ce (@onc_ce) December 20, 2023
16) Almost twice as many patients in #luspatercept arm vs #ESA arm (60.4% vs 34.8%) reached primary endpoint (transfusion independence ≥12 weeks in weeks 1-24 and hemoglobin increase by 1.5 g/dL). pic.twitter.com/lJnQFnEDst
— @onc_ce (@onc_ce) December 20, 2023
18) #Luspatercept was recently approved by @US_FDA for the treatment of #anemia in ESA-naïve LR-#MDS adult transfusion-dependent patients. Now 1L !
— @onc_ce (@onc_ce) December 20, 2023
20) #IMerge studied the drug #imetelstat. #Telomerase activity looks to be higher in #MDS cells vs normal counterparts. Imetelstat is a potent, 1st in class telomerase inhibitor. Study rationale: imetelstat targets MDS cells & will improve #cytopenias/ ⬇️transfusion burden. pic.twitter.com/qYcDENhE03
— @onc_ce (@onc_ce) December 20, 2023
21b) Cytopenias are a major adverse event with #imetelstat. Clinically significant bleeding and rates of infection were similar to placebo.
— @onc_ce (@onc_ce) December 20, 2023
23) @ErnstoffMarc our institute chair at @RoswellPark @RoswellHemOnc during his time there, used to tell us about cancer stage migration using ‘Will Rogers Phenomenon’ – ‘When the Okies left OK & moved to CA, they raised the average intelligence level in both states’. pic.twitter.com/I8VVV77YLf
— @onc_ce (@onc_ce) December 20, 2023
24b) This remains to be determined. More prospective research needed to validate these provocative findings. pic.twitter.com/jFdOMTRnCh
— @onc_ce (@onc_ce) December 20, 2023
25b) As per graph below, the answer is c, ~3.5 g/dL. Good job! pic.twitter.com/TvWRvVnKGf
— @onc_ce (@onc_ce) December 20, 2023
26b) . . . to receive #alloHSCT at various time points during the disease course (#ASH23 abstract #197). Study concluded that in IPSS-M moderate high, high and very high-risk groups, immediate alloHSCT was associated with better survival. pic.twitter.com/Ftbn43eD3w
— @onc_ce (@onc_ce) December 20, 2023
28a) I'd go with a!
— @onc_ce (@onc_ce) December 20, 2023
Now, what is your best interpretation of the graph shown in 28b:
a. #Imetelstat may have disease modifying activity
b. Imetelstat may have cytotoxic properties
c. Imetelstat helps restore normal hematopoiesis
d. Imetelstat reverses all chromosomal aberrations
28c) The correct answer is a. As in the plot above, mutational data ➡️a ⬇️of the myelodysplastic clones with #imetelstat exposure, suggesting the drug has disease-modifying activity.
— @onc_ce (@onc_ce) December 20, 2023
See also the full #IMerge ms in @TheLancet at https://t.co/RpVkW3b1lD.
29b) The correct answer is b. ‘b’ represents the cohort where #ESAs historically have had the best responses and may still be an option.
— @onc_ce (@onc_ce) December 20, 2023
30b) . . . the imbalanced TGF-beta signaling (akin to #luspatercept but w/certain mechanistic distinctions). KER-050 acts on both early & late-stage #hematopoiesis. pic.twitter.com/VfE1EcsbC1
— @onc_ce (@onc_ce) December 20, 2023
30d) KER-050 appeared to improve platelet counts and improved FACIT fatigue scores in responders.
— @onc_ce (@onc_ce) December 20, 2023
Re #FACIT, see 🔓 https://t.co/w7qagc0hL8.
Ph 3 registration evaluating KER-050 likely will be next. pic.twitter.com/6ofYSiIaYx
31b) In #MATTERHORN, 50% of pts were #ESA-refractory. Numerical benefit for #roxa, but < statistical signif ➡️ early term of study.
— @onc_ce (@onc_ce) December 20, 2023
👉Response rate in placebo arm 33.3%? 🤔
👉In post hoc analysis, pts w/higher transfusion burden (>/=2 pRBCs q4 wk) showed superiority for roxa. pic.twitter.com/M5fgSe1AAS
33a) More and more data is being presented on inflammation in #MDS, especially in low risk disease. #ASH23 abstracts that explored inflammation:
— @onc_ce (@onc_ce) December 20, 2023
33c) Would be interesting to see the role of Interleukin-1 receptor-associated kinase 1/4 (IRAK-1/4) inhibition in LR-#MDS (trial in progress; abstract #3247)
— @onc_ce (@onc_ce) December 20, 2023
34) Lots happening in low-risk #MDS: from exhilarating preclinical discoveries (from plenary to exciting posters) to eagerly awaited FDA decisions regarding first-in-class disease modifying therapies. 2024 will be the year to look out for #myeloid malignancies! Stay tuned!
— @onc_ce (@onc_ce) December 20, 2023
35) Thank you so much for joining us, and hats off to @CloneTracker for an awesome recap of #LR_MDS news from #ASH23. Now grab your 🆓 CE/#CME at https://t.co/am1MFmy3nZ and FOLLOW US for more #MedEd!
— @onc_ce (@onc_ce) December 20, 2023