GVHD Prophylaxis Including ATG Remains Standard of Care for HLA-Compatible Unrelated Donor Hematopoietic Cell Transplantation: Results from a Large Randomized Controlled Trial Comparing ATG and PTCY

Presenter: Matthias Stelljes

• This phase 3 RCT compared PTCy-100 (50 mg/kg on days +3/+4; N=383) vs. ATG-30 (10 mg/kg on days -3 to -1, N=257) for GVHD prophylaxis in 640 alloHCT patients (median age: 63 years, disease risk index: high/ very high for 57% patients).
• Myeloablative, sequential, reduced, or non-myeloablative conditioning was used in 16%, 18%, 66%, and 0.2% of patients, respectively. At 2 years, OS (PTCy vs ATG): 68% vs. 75% (adj. HR 1.34, p=0.85 for non-inferiority).
• Day +100 cumulative incidence (CI) of acute GVHD II-IV (PTCy vs. ATG): 21% vs. 7% and of GVHD grade III-IV: 26% vs. 7%.
• 1-year CI of chronic GVHD: 24% vs. 6% and of severe chronic GVHD: 40% vs.10. GVHD- and relapse-free survival (GRFS) at 2 years after HCT:48% vs. 40% (adj. HR 0.85, p=0.16). CI of relapse at 2 years after HCT: 26% vs. 31% (adj. HR 0.86, p=0.32).
• Non-relapse mortality (NRM) was higher with PTCy (13% vs 7%, HR 1.86, p=0.02), mainly due to infections.
• GVHD prophylaxis with ATG-30 along with tacrolimus and MMF remains current standard of care for HLA-compatible unrelated donor HCT.
• GVHD prophylaxis with ATG-30 in combination with tacrolimus and MMF remains current standard of care for HLA-compatible unrelated donor HCT. Considering the potency of PTCy to prevent chronic GVHD, options to improve immune reconstitution should be explored.

Selinexor Plus Ruxolitinib in Janus Kinse Inhibitor–Naïve Myelofibrosis: Phase 3 SENTRY Trial

Presenter: Claire Harrison

• JAKi, such as ruxolitinib (R), is the front-line therapy for MF, but very few patients (1/3) achieve spleen volume reduction of ≥35% (SVR35).
• Selinexor (S), an XPO1-mediated nuclear export inhibitor, has biological activity in MF and has shown synergistic action with R in MPN models.
• The phase 3 SENTRY trial randomized 353 JAKi-naïve MF patients 2:1 to S 60 mg weekly + R or placebo + R.
• At week 24, higher proportion of patients in S+R group achieved SVR35, vs. R group (49.8% vs 28.0%; OR 2.58; p<0.0001). Mean SVR was higher with S+R vs. R (−40.0% vs. −26.7%).
• The absolute mean change in total symptom score (AbsTSS) change was −9.9 vs. −10.9 (p=0.825).
• OS was higher in S+R group (HR 0.43; p=0.022), with SVR35 responders showing 98% survival at week 72 vs. 88% in nonresponders.
• At week 24, driver mutation VAF reduction ≥20% occurred in 32.0% vs. 23.9%. Amongst patients with detectable peripheral blasts at baseline, the circulating peripheral blasts decreased with S+R but not with R. S+R maintained 0% peripheral blasts in patients without blasts at baseline.
• TEAEs ≥grade 3 were reported in 70.1% vs. 50.0%, treatment discontinuation was reported in 14.5% and 8.6% patients in S+R and R group, respectively.
• S+R achieved rapid, deep, and sustained SVR35, matched R in symptom relief, showed manageable safety, and improved OS.
• Promising OS was observed, and SVR35 responses predicted OS in both the ph1 and ph3 studies, positioning S+R as the first JAKi-naïve MF.

Efficacy and Safety of Mitapivat in Sickle Cell Disease: Results from the Global, Randomized, Phase 3 RISE UP Trial

Presenter: Biree Andemariam

• The phase 3 RISE UP trial evaluated the efficacy and safety of mitapivat vs. placebo in patients with SCD.
• A total of 207 SCD patients (median age: 25 yrs, 57.5% females) were randomized 2:1 to mitapivat 100 mg BID (n=138) vs. placebo (n=69). Baseline Hb was ~8.6 g/dL.
• Hb response (≥1 g/dL increase) occurred in 40.6% with mitapivat vs. 2.9% with placebo (p<0.0001). Mean Hb gain with mitapivat was +0.74 g/dL (95% CI 0.49–1.00; p<0.0001), and indirect bilirubin fell by −16.91 μmol/L (p<0.0001), as compared to placebo.
• The annualized sickle cell pain crises rates were 2.62 vs. 3.05 (p=0.1213). Responders showed improvement in OS predictors: SCPC 2.20 vs. 2.98, hospitalizations 1.16 vs. 1.76, and PROMISE fatigue 13a T-score change −5.19 vs. −2.55 (clinically meaningful change: 4.1).
• Serious AEs occurred in 20.3% vs. 29.0%, with no safety signals observed in the mitapivat group.
• Mitapivat showed significant hematologic benefits, improved hemolysis, and had favorable tolerability.

Efficacy and Safety of Luspatercept in Patients with Myelofibrosis on Janus Kinase Inhibitors who Require Red Blood Cell Transfusions: Primary Analysis of the Phase 3 Independence Trial

Presenter: Francesco Passamonti

• The phase 3 INDEPENDENCE trial evaluated the efficacy and safety of luspatercept (LUSPA) in 313 patients with MF anemia.
• Patients on stable JAKi therapy and red blood cell transfusion (RBCT) dependence were randomized 2:1 to LUSPA (n=208) vs. placebo (n=105).
• 70.6% of patients had high RBCT burden (≥6 U/12 wks), median age 73 yrs, time since MF diagnosis was 4.0 yrs, baseline transfusion burden (TB) was 7 U/12 wks, time since first RBCT was 17.6 mos, and Hb level was 7.6 g/dL.
• A higher proportion of patients treated with LUSPA achieved RBC-TI ≥12 wks (23.1% vs. 13.3%; p=0.0674).
• Secondary endpoints favored LUSPA, with consistent reductions in transfusion burden (RBC -TI 16: RBC and Hb increases ≥1 g/dL; 19.2% vs. 11.4%), greater reduction in RBC burden from baseline ≥50% and ≥4 U/12 weeks (40.9% vs. 22.9%).
• Serious TEAEs occurred in 44.0% vs. 38.1%, but exposure-adjusted incidence was similar (64.3 vs. 62.4/100 pt-yrs).
• Treatment with LUSPA was associated with clinically meaningful improvements in anemia and transfusion independence with a manageable safety profile, supporting its role as a novel therapy for MF-associated anemia with limited therapeutic options.

Early versus Delayed ESA in Lower-Risk Non -Transfusion-Dependent MDS: Final Phase III EPO-PRETAR Results on Transfusion Dependence and Erythroid Response

Presenter: Sophie Park

• The phase 3 EPO-PRETAR trial compared early vs. delayed initiation of EPO ALFA in non- RBC transfusion-dependent MDS patients.
• A total of 84 patients were randomized to early EPO ALFA (arm A: initiation at inclusion, baseline Hb 9–10.5 g/dL) or delayed EPO ALFA (arm B: initiation at the center-defined Hb threshold for RBC transfusions <9 g/dL)
• The median time to EPO start was 0.2 mths (Arm A) vs. 16.2 mths (Arm B). RBC transfusion dependence (TD) occurred in 49% vs. 46% (HR 0.90; p=0.74), with 36‑month TD probabilities of 43.4% vs. 39.2%.
• At week 12, erythroid response (HI-E IWG 2018; hemoglobin increase ≥1.5 g/dL vs. nadir in the preceding 16 weeks) was achieved in 85% vs. 55% (RR 1.57; p=0.003).
• Median response duration of erythroid response was 32.7 vs. 24.9 months. OS (deaths: 47% vs. 41%) and PFS (51.0 vs. 38.0 months; HR 0.91; p=0.75) were similar in both arms.
• The 36‑month PFS was 57.0% vs. 58.3%. AML progression, and safety were similar between arms.
• The treatment was well tolerated.
• Early EPO ALFA improved hematologic response but not transfusion dependence or survival.
• Timing of ESA initiation should align with symptom burden and patient preference, balancing early hematologic gains against no proven benefit for transfusion independence or survival.

Etavopivat Reduces Transfusion Requirements in Adults and Adolescents with Transfusion-Dependent Alpha- or Βeta-Thalassemia: Results from the Open-Label Phase 2 GLADIOLUS Study

Presenter: Ashutosh Lal

• The phase 2 GLADIOLUS study evaluated the safety and clinical activity of etavopivat in 20 transfusion-dependent thalassemia (TDT) patients (mean age 21.5 years, mean 19.3 RBC units/24 wks pre-study).
• The study participants received oral etavopivat 400 mg QD.
• Among 19 evaluable participants, 89% achieved ≥20% reduction and 79% achieved ≥33% reduction in RBC transfusion units over any continuous 12-wk period vs. baseline.
• Mean relative transfusion burden reductions were 15.3% at wk 12, 11.9% at wk 24, and 10.9% at wk 48.
• Pre-transfusion Hb rose initially but normalized as transfusions with etavopivat were reduced.
• A sustained ATP increase and 2,3-DPG decrease was observed, supporting the mechanism of action of etavopivat.
• Etavopivat was well tolerated, with mainly mild/moderate TEAEs and no new safety signals.
• Etavopivat lowered transfusion needs in TDT with favorable efficacy, and no new safety issues—supporting further investigation.

Combination of Thrombopoietin Receptor Agonists and Rituximab in Relapsed/Refractory Immune Thrombocytopenia: A Multicenter Real-World Study

Presenter: Hong Tian

• This multicenter retrospective study evaluated efficacy, durability, safety, and predictors of treatment-free remission (TFR) in 161 patients with relapsed or refractory ITP. All patients were treated with combination therapy with TPO-RAs and rituximab.
• The median age of the study population was 42 years, and median disease duration was 24 months. Nearly 88% of the patients had suffered at least one relapse and 93% were refractory to prior therapies. combination therapy with TPO-RAs and rituximab achieved an ORR of 83% (CR 43%, PR 40%). After a median follow-up of 22 months, 30% attained TFR, with median time to TFR of 17 weeks.
• Rituximab restored platelet response in 28.9% of primarily refractory and 40.0% of secondarily resistant patients.
• AE occurred in 14.3%, mostly grade 1–2, with no treatment-related deaths. The regimen was effective and well tolerated.
• TPO-RAs plus rituximab was effective and well-tolerated in relapsed/refractory ITP, yielding high responses, durable remission, and restored TPO-RA sensitivity.

31^st European Hematology Association Congress  (EHA 2026),11^th –14^th, 2026, Stockholm, Sweden.