2) Fortunately our intrepid correspondent & returning expert faculty Dr Claire Harrison @harrisoncn1, Prof of Haematology at the Guy’s & St. Thomas’ NHS Foundation Trust @GSTTnhs in #London 🇬🇧was at #EHA2026 and has prepared this update on 🔑data. pic.twitter.com/0VhOUZReOV
— @onc_ce (@onc_ce) June 17, 2026
4) @harrisoncn1 has previously introduced us to the basics of #MF #anaemia. Her prior tweetorial at https://t.co/kOg9nNEmcp still available for 🆓0.75h CE/#CME. She summarized the #pathophysiology with this graphic from 🔓https://t.co/olkFjjeKLF and . . . pic.twitter.com/LJcesL01j9
— @onc_ce (@onc_ce) June 17, 2026
6) Current @NCCN guidelines for the management of #MF #anemia are shown here, from 🔓 https://t.co/36VqeWDAIm: pic.twitter.com/wp6w2xhgG5
— @onc_ce (@onc_ce) June 17, 2026
8a) It's interesting to see #luspatercept, a recombinant #fusion protein that prevents downstream signaling of the SMAD2 and SMAD3 pathways, thereby supporting late-stage erythropoiesis. Interesting because early readout of the Ph 3 #INDEPENDENCE trial . . .
— @onc_ce (@onc_ce) June 17, 2026
8c) However, some clinically meaningful secondary benefits e.g. ⬆️hemoglobin & ⬇️ transfusion burden in certain subgroups were met, and so #luspatercept is IN the guidelines . . .
— @onc_ce (@onc_ce) June 17, 2026
9) #Luspatercept, now with updated Ph3 #INDEPENDENCE data at #EHA2026 in #myelofibrosis-associated #anemia, is best described as which of the following? #MedEd #hemeonc #CME
— @onc_ce (@onc_ce) June 17, 2026
11) At #EHA2026, Passamonti presented updated primary results of Ph3 #INDEPENDENCE ([#luspatercept + #JAKi] vs [placebo + JAKi]) in transfusion-dependent #MF #anemia). What was the headline finding for the primary RBC-TI endpoint?
— @onc_ce (@onc_ce) June 17, 2026
13) So here we go.
— @onc_ce (@onc_ce) June 17, 2026
The design of INDEPENDENCE is straightforward: Ph3 DBRCT, 313 adults w/ #MPN-associated myelofibrosis on a stable #JAK2i + RBC transfusion-dependent #anemia. Randomized to luspatercept vs. placebo SC q3wks, added on to ongoing JAKi. pic.twitter.com/SJ2hByeiZi
15a) Why combine? JAKi's (#ruxolitinib, #fedratinib) tame splenomegaly & symptoms but are myelosuppressive — worsening anemia & transfusion burden, which is independently prognostic for shorter OS in MF.
— @onc_ce (@onc_ce) June 17, 2026
See 🔓 https://t.co/5EcXjIjxCd
16a) #Luspatercept is an activin receptor ligand trap that dampens SMAD2/3 signaling to rescue late-stage erythroid maturation: an MOA distinct vs #EPO & orthogonal to #JAK_STAT.
— @onc_ce (@onc_ce) June 17, 2026
17a) July 2025 BMS topline: INDEPENDENCE missed its primary endpoint of RBC-TI ≥12 wks (p=0.0674), but with a numerically & clinically meaningful improvement favoring #luspatercept . . .
— @onc_ce (@onc_ce) June 17, 2026
18) #Biology: #MF #anemia is multifactorial (fibrosis, splenic sequestration, inflammation, iron dysreg, cytokine storm), not the relatively "clean" #SMAD2/3-driven ineff erythropoiesis luspatercept overcame in #MDS_RS & β-thalassemia. Less mechanistic overlap = smaller effect.
— @onc_ce (@onc_ce) June 17, 2026
19b) … (b) ongoing #JAKi-driven #myelosuppression counteracting luspatercept's pro-erythroid effect; (c) Day 169 unblinding/crossover for non-responders may have diluted ITT estimates.
— @onc_ce (@onc_ce) June 17, 2026
21a) Pts from China were slightly younger, had lower Hb levels, a higher proportion w/DIPSS Intermediate-1 & sEPO ≥ 500 U/L, & a shorter time since first RBC transfusion vs pts from ROW, suggesting a more advanced disease population at baseline.
— @onc_ce (@onc_ce) June 17, 2026
22a) 🔑secondary EPs were all nominally in favour of #luspatercept as seen & are relevant clinically. Pts treated w/luspatercept vs placebo ➡️RBC-TI ≥ 12 & mean Hb ⬆️≥ 1 g/dL more rapidly.
— @onc_ce (@onc_ce) June 17, 2026
23) The #luspatercept safety profile was gen manageable & consistent w/prior studies & underlying advanced #MF disease setting. No clear treatment–related trend in causes of death was observed; some intriguing trends regarding bone fractures & AML are noted but not significant. pic.twitter.com/sDGedpjaPA
— @onc_ce (@onc_ce) June 17, 2026
24b) Improvements were consistent across most subgroups, except for pts enrolled in the APAC region & pts w/baseline sEPO ≥ 500 U/L: a testimony to complexity of delivering anemia studies! #Luspatercept safety profile was manageable & consistent w/that expected in advanced MF
— @onc_ce (@onc_ce) June 17, 2026
26) #MPN are late entrants to the targeted therapy field. 2 presentations to highlight here: update w/INCA 033989. In the #MF population both JAKi naïve, relapsed refractory, intolerant (RRI) and combo cohorts have been tested and the tolerability, I would say, is remarkable.
— @onc_ce (@onc_ce) June 17, 2026
28) In the trial, spleen & symptom responses were impressive for a largely 2L population where baseline scan was taken pre-JAKi washout. Note there were populations of JAKi experienced & naïve pts, & different types of #CALR mutations are called out with colors indicating dose. pic.twitter.com/3IbMrVxo5H
— @onc_ce (@onc_ce) June 17, 2026
30) And finally we saw reductions in #blasts, circulating mutant precursors, and improvements in marrow morphology. pic.twitter.com/fTryLaYJoh
— @onc_ce (@onc_ce) June 17, 2026
32) Here are the rationale for Type II #JAK inhibition and the structure of AJ1-11095 which has a highly specific #kinome: pic.twitter.com/0jwQzcHs1x
— @onc_ce (@onc_ce) June 17, 2026
34) However, this was at the cost of quite significant anemia at least in the first 24 weeks, as noted below the only grade 3 or 4 AEs were cytopenias. The value of supportive care with drugs such as #luspatercept with this #JAKi to improve #anemia here is yet to be tested.
— @onc_ce (@onc_ce) June 17, 2026
36) Finally, in a late breaking abstract the results of the #SENTRY trial in JAKi naïve patients were presented. pic.twitter.com/cQ214wVRRL
— @onc_ce (@onc_ce) June 17, 2026
38) Like many other combo studies, study met Spleen but not Symptoms EPs.
— @onc_ce (@onc_ce) June 17, 2026
👉But in unprecedented findings: a survival benefit HR 0.43, correlating w/spleen response. This trend also seen in Ph 1. This #OS correlated w/SVR35 that were rapid & deep; SVR35 also correlated w/VAF ⬇️ pic.twitter.com/aprrkbFLoZ
40) The full study is accepted in JCO and we await further information. pic.twitter.com/NRHDhhy3AQ
— @onc_ce (@onc_ce) June 17, 2026
41b) 2⃣In the plenary: 🔥off the press data with #Selinexor plus #Ruxolitinib in #JAKi naive #MF showing a #survival benefit correlating with rapid, deep, sustained SVR and other early signs of disease modification. Do watch for the 48 week data.
— @onc_ce (@onc_ce) June 17, 2026
41d) 4⃣ Finally, the novel Type II #JAKi from AJAX showing deep responses, and in resistant #MF patients, with the promise of driver mutation change as well.
— @onc_ce (@onc_ce) June 17, 2026
We're in a wonderfully active space!
42) Congratulations! You are up to date from #EHA26 on advances in therapy for #anemia associated with #myelofibrosis, AND you also just earned 1 hour of 🆓CE/#CME credit! Claim your certificate now at https://t.co/ppwAnvs6XM.
— @onc_ce (@onc_ce) June 17, 2026
Many thanks to our 🏆expert faculty @harrisoncn1!