1b) @AmyDeZern is Director, Bone Marrow Failure & #MDS Program at #Hopkins and has expertise in #aplastic #anemia, #myelodysplastic syndromes, paroxysmal nocturnal hemoglobinuria #PNH, acute myeloid #leukemia #AML, & bone marrow transplantation #BMT. pic.twitter.com/d7HD4YDy3t
— @onc_ce (@onc_ce) September 12, 2023
3) Therapeutic goals are constant for pts with #LR_MDS:
— @onc_ce (@onc_ce) September 12, 2023
🥅establish appropriate monitoring plan
🥅decrease transfusion needs
🥅decrease impact to QoL
🥅lower risk of transformation to AML
🥅maximize benefit
🔓 https://t.co/LvanH0OPQc
5) There are multiple imp't considerations that contribute to a tx paradigm for #LR_MDS
— @onc_ce (@onc_ce) September 12, 2023
(ATG: antithymocyte globulin; ESA: erythropoiesis-stimulating agent; HMA: hypomethylating agent; MDS-RS: #MDS with ringed sideroblasts; MLD, multilineage dysplasia)
🔓 https://t.co/Pb0sMHL2QJ pic.twitter.com/ouCaUSOxu4
6a) Transfusion dependency #TD is an independent prognostic factor in #MDS. The detrimental effect on survival is related to the severity of transfusion requirement and is more noticeable in low-risk patients. Here's data from 2007 https://t.co/c2eVdEWVaQ : pic.twitter.com/4LjQF83ajd
— @onc_ce (@onc_ce) September 12, 2023
7a) These findings were replicated 11 years later 🔓https://t.co/WTfZbnwiAL, looking at pts w/low- or unspecified-grade #MDS, treated with #ESA. ESA tx was most common tx approach, both frontline and second-line.
— @onc_ce (@onc_ce) September 12, 2023
7c) These data were seen in 2016 as indicating the critical importance for treatment beyond #ESA to reduce transfusion burden among pts with #MDS, in both the frontline and relapsed settings.
— @onc_ce (@onc_ce) September 12, 2023
That 🆕 tx? An erythroid maturation agent #EMA
9a) The #MOA for an #ESA like #luspatercept is unique: it is a recombinant #fusion protein that binds transforming growth factor β superfamily ligands to reduce #SMAD2 and #SMAD3 signaling, preventing activation of TGF-beta superfamily members that➡️ineffective #erythropoiesis pic.twitter.com/AyFV4BUU7U
— @onc_ce (@onc_ce) September 12, 2023
10) In #MEDALIST (🔓https://t.co/JMH5XtjY8x), @FenauxP et al showed that #luspatercept ⬇️severity of anemia in pts w/LR-#MDS-RS who had been receiving regular transfusions & were refractory to or unlikely to respond to #ESA. pic.twitter.com/3kutMQlIth
— @onc_ce (@onc_ce) September 12, 2023
12) Enter Ph 3 #COMMANDS (NCT03682536, @garciamanero et al): 1L comparison #EMA vs #ESA: efficacy & safety of #luspatercept versus #epoetin alfa for the treatment of anemia due to IPSS-R LR-MDS in ESA-naïve patients who require regular RBC transfusions
— @onc_ce (@onc_ce) September 12, 2023
🔓https://t.co/q7ZoJsj2S2 pic.twitter.com/muYYsypYNS
14) The study was well-designed and well-executed, with very comparable baseline characteristics between the two groups and an inclusion criterion of baseline #EPO <500 for enrollment to avoid bias against the #ESA arm. pic.twitter.com/crWj37xwh5
— @onc_ce (@onc_ce) September 12, 2023
15b) Achievement of the primary endpoint favored #luspatercept or was similar to #epoetin alfa for all subgroups analyzed pic.twitter.com/VcmGYJAUmW
— @onc_ce (@onc_ce) September 12, 2023
17) Safety signals were similar to those seen for #luspatercept in #MEDALIST. pic.twitter.com/SDoMGaDIt0
— @onc_ce (@onc_ce) September 12, 2023
19a) So . . . Practical Considerations from #COMMANDS:
— @onc_ce (@onc_ce) September 12, 2023
🩸#Luspatercept shows superiority vs #ESAs, with ~2x patients achieving both #TI and #Hb increase
🩸Luspatercept delivers more durable responses, with nearly 2.5 years of median TI, which is ~1 year longer than ESAs
(cont)
19c)
— @onc_ce (@onc_ce) September 12, 2023
🩸Further evaluation of the mature dataset and longer follow-up are planned, and cost must be considered as #luspatercept $$$$ > #ESA $$
20a) .@USFDA agrees. On 8/28/23 the indication for #luspatercept was expanded to 1L 🥇tx for anemia in #ESA-naïve adult patients with very low- to intermediate-risk myelodysplastic syndromes (#MDS) who may require regular #RBC #transfusions. pic.twitter.com/Xkt2hLKO3i
— @onc_ce (@onc_ce) September 12, 2023
20c) Further practical guidance:
— @onc_ce (@onc_ce) September 12, 2023
🔑Recommendation for #HTN management: Monitor #BP prior to each administration
🔑Manage new-onset HTN or exacerbations of pre-existing HTN using #antihypertensives
🔑Monitor for fatigue and diarrhea
22) #Imetelstat has disease-modifying potential to selectively kill malignant stem & progenitor cells, enabling recovery of blood cell production pic.twitter.com/KOkr82DjKB
— @onc_ce (@onc_ce) September 12, 2023
23b) Treatment options for patients with ESA-relapsed/refractory/ineligible lower-risk MDS now include #luspatercept but also include #HMAs, #IMiDs, and supportive care alone or with #chelation therapy
— @onc_ce (@onc_ce) September 12, 2023
24) @Dr_AmerZeidanof @Yale, one of our expert @onc_ce faculty, led the Ph 3 #IMerge study of #imetelstat, from which data were also presented at #ASCO2023.
— @onc_ce (@onc_ce) September 12, 2023
🔓 https://t.co/iGn3ULJ169 pic.twitter.com/wmAjpL123w
26a) #Imetelstat resulted in a significant & sustained #RBC transfusion independence #TI in 40% of these heavily transfused patients. The response was also durable & accompanied by median #Hb ⬆️of 3.6 g/dL. pic.twitter.com/5UUQDcDV8q
— @onc_ce (@onc_ce) September 12, 2023
26c) … and this correlated with duration of transfusion independence #TI and hemoglobin rise, therefore suggesting a disease-modifying potential of #imetelstat. pic.twitter.com/oFmVu756VM
— @onc_ce (@onc_ce) September 12, 2023
27b) summary (2/2)
— @onc_ce (@onc_ce) September 12, 2023
✔️#ESA-refractory patients require newer agents with goal of eliminating transfusion burden-> Different MOAs are needed
✔️#MEDALIST established #luspatercept as 2L & #COMMANDS as 1L
✔️IMerge supports use of #imetelstat as a novel MOA in ESA-refractory MDS
28b) It is c, #luspatercept, a first-in-class #EMA shown to be safe and effective first as 2L in #MEDALIST and then as 1L for management of #anemia in #COMMANDS. pic.twitter.com/ceb5RtDZZw
— @onc_ce (@onc_ce) September 12, 2023
28d) It's a, ring #sideroblast negative patients. RS+ patients followed the other subgroups in #COMMANDS & benefitted from #luspatercept. It's important to ✔️RS status prior to luspatercept use, but the FDA indication does not exclude RS- patients. pic.twitter.com/4XTK45sonZ
— @onc_ce (@onc_ce) September 12, 2023
29) And you just earned 0.5hr 🆓CE/#CME credit! You can claim your certificate at https://t.co/KZjuFQCHjB. Do that, and then FOLLOW US to keep grabbing #MedEd from expert #hematology #oncology faculty, delivered entirely on Twitter! .@AmyDeZern 🙏you for joining!
— @onc_ce (@onc_ce) September 12, 2023