Nico Gagelmann: Highlights from EHA 2025 – Breakthroughs in ET, Myelofibrosis, MM, MDS, and BPDCN

Nico Gagelmann, Chair of the CAR-T for plasma cell disorder committee at the EBMT, shared a post on X:

“The EHA 2025 is the prime hematology event in Europe with excellent educational events and top-notch science!m Congrats, European Hematology Association, YoungEHA, for building such an amazing community.

Here are selected abstract presentations to look out for:

Promising new therapy for CALR-mutant ET

Early Phase 1 data show INCA33989, a first-in-class antibody targeting mutCALR, is safe and effective in patients with high-risk ET.

Key Highlights:

• Targets mutCALR in ~25% of ET patients
• 79% overall response rate (66% complete response)
• Platelet count reductions seen as early as 4 weeks
• 88% had decreased mutCALR allele burden
• Well-tolerated with no dose-limiting toxicities or thrombocytopenia
• Most side effects were mild (e.g., fatigue, mild infections)

INCA33989 could represent a precision, mutation-targeted approach for ET patients resistant to current therapies.

A major step forward in MPN care

New results from the Phase III SURPASS-ET trial

Key Highlights:

• 43% of ropeg patients achieved sustained response vs. 6% with anagrelide
• Fewer thrombotic events, disease progression, and serious side effects with ropeg
• Greater symptom control and allele burden reduction

Already approved for polycythemia vera, ropeg now shows promise as a superior second-line therapy for ET.

Promising option for early-stage myelofibrosis

New data show that Ropeginterferon alfa-2b (Ropeg-IFN-α2b) is safe and effective in patients with pre-fibrotic or low/intermediate-1 risk myelofibrosis, a population with limited treatment guidance.

Key Highlights:

• Blood count responses: Hemoglobin – 76.2%
• WBC – 79.4%, Platelets – 100%
• JAK2V617F VAF reduction: 44%
• CALR VAF reduction: 43%
• Spleen size reduction: 53%
• Symptom improvement (≥50% MPNSAF-TSS reduction): 42%
• Most side effects were mild to moderate, including fatigue, hair loss, and mild liver enzyme elevations

Ropeg-IFN-α2b shows strong clinical, hematologic, and molecular activity in early-stage MF, with a favorable safety profile and potential to delay disease progression.

Big news in multiple myeloma

Early results from the Phase 1 study of JNJ-5322, a next-gen trispecific T-cell redirecting antibody, show remarkable efficacy in RRMM.

Key Highlights:

• JNJ-5322 targets BCMA + GPRC5D with a low-affinity CD3 domain to maximize tumor attack while minimizing side effects
• At the recommended dose (100 mg Q4W):
• 100% response rate in patients naïve to BCMA/GPRC5D therapies
• 86% overall response rate in treated patients
• Most CRS events were mild (no grade ≥3)
• Lower GPRC5D-related side effects vs other bispecifics

A potential CAR-T-like response, without the complexity of cell therapy.

Congrats, Rakesh Popat et al.

Cilta-cel and Delayed Neurotoxicity: Key Risk Factor Identified

Key Highlights:

• 235 patients, 9.7% developed delayed neurotoxicity
• 3.8% IEC-PKS, 6.4% IEC-NP

Top predictor:

• Peak ALC ≥3 x10⁹/L post-infusion → 30% risk vs 3% without

Other risks for IEC-PKS:

• Age >75, high tumor burden, ICANS, elevated ferritin

Treatment:

• IEC-NP: 85% responded to steroids
• IEC-PKS: Early cyclophosphamide led to rapid symptom relief

Peak ALC may guide early intervention to prevent or manage cilta-cel neurotoxicity. Congrats Rafael Fonseca, Yi Lin et al.

Breakthrough for extramedullary disease in myeloma

New Phase 2 data from RedirecTT-1 show that combining Talquetamab + Teclistamab delivers strong, durable responses in RRMM patients with extramedullary disease – a group historically resistant to treatment.

Key Highlights:

• 90 patients
• 79% overall response rate (52% ≥ complete response)
• 83% ORR in patients with prior CAR-T therapy
• 9-month PFS: 64% | OS: 80%
• Most responses deepened/held after switching to monthly dosing
• CRS in 78% (all grade 1/2)
• ICANS in 12% (mostly mild)
• Common AEs: taste changes, skin/nail effects, infections (mostly early and manageable)

This is the largest EMD-specific study to date, and results rival those of CAR-T, with off-the-shelf accessibility.

New Approach for High-Risk MDS: BEXMAB Trial Results

Bexmarilimab, a first-in-class macrophage checkpoint inhibitor, shows promising early results in combination with azacitidine for patients with high-risk myelodysplastic syndrome (HR MDS)—a group with few effective options, especially after HMA failure.

Key Highlights:

• 100% response rate in initial frontline MDS patients
• 80% ORR in relapsed/refractory (r/r) MDS (65% by updated IWG2023 criteria)
• Median OS of 13.4 months in r/r MDS—more than double historical outcomes (<6 months)
• No dose-limiting toxicities in dose escalation
• Most AEs were manageable; only 13.7% were related to bexmarilimab
• Doses of 3mg/kg and 6mg/kg being evaluated for optimal efficacy/tolerability

The BEXMAB study offers a potential immunotherapy-based breakthrough for both frontline and r/r HR MDS, patients with urgent unmet need.

Congrats, Amer Zeidan, Naval Daver et al.

New hope for BPDCN patients

The Phase 1/2 CADENZA trial shows that PVEK, a first-in-class CD123-targeting antibody-drug conjugate, delivers high response rates and manageable safety in blastic plasmacytoid dendritic cell neoplasm (BPDCN).

Key Highlights:

• 70% CR + CRc rate
• 85% overall response rate
• Median OS: 16.6 months
• 92% response rate in those bridged to stem cell transplant

Relapsed/Refractory (R/R) Results:

• 14% CR + CRc | 35% ORR
• Responses similar to or without prior tagraxofusp

Safety Snapshot:

• No capillary leak syndrome or treatment-related deaths
• Most common side effect: low-grade peripheral edema
• Rare, reversible veno-occlusive disease (2%)

Given as a short IV outpatient infusion every 21 days, PVEK could be a powerful new option for both newly diagnosed and previously treated BPDCN patients.

Congrats, Naveen Pemmaraju.”

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