EHA 2023 Late-Breaking Abstracts Offer Sneak Peek at the Future of Hematology

The late-breaking oral session at the European Hematology Association (EHA) 2023 Congress featured newly emerged data from abstracts submitted after the deadline, including outcomes from trials in polycythemia vera, acute myeloid leukemia (AML), and more.

As introduced by session cochair Konstanze Döhner, MD, of the University Hospital Ulm in Germany, the 5 abstracts were selected by the scientific committee and advisory board for their high relevance to the hematological community and their diversity of countries, disease states, and type of research.

First, Marina Kremyanskaya, MD, PhD, of the Icahn School of Medicine at Mount Sinai, presented findings from a withdrawal analysis of the phase 2 REVIVE study of rusfertide, a hepcidin memetic, to control hematocrit levels in patients with polycythemia vera who had a high phlebotomy burden. Patients received a subcutaneous injection once weekly, then were randomly assigned at week 29 to either receive placebo or maintain the rusfertide dose.

Rusfertide met its primary efficacy end point of response as defined by not needing phlebotomy within 12 weeks (69.2% vs 18.5% in the placebo arm; P = .0003). The investigational drug was generally well tolerated, with 83% of the treatment-emergent adverse events (TEAEs) having a grade of 1 or 2; there were no grade 4 or 5 TEAEs.

“Rusfertide demonstrated favorable effects on several patient-reported outcomes, such as fatigue, problems with concentration, pruritus, and inactivity, and that was particularly seen in patients who had more severe symptoms at baseline,” Kremyanskaya said. She noted that the phase 3 VERIFY trial is ongoing to investigate rusfertide vs placebo, and there is a follow-on 2-year extension study opening this year for the patients who completed the REVIVE study.

Next, Mark J. Levis, MD, PhD, of Johns Hopkins University School of Medicine, took the stage to present findings from a randomized trial of the FLT3 inhibitor gilteritinib as posttransplant maintenance therapy for FLT3-ITD AML. These patients have a high rate of relapse, Levis noted, especially if they have minimal residual disease (MRD) before transplant.

In the worldwide randomized controlled trial, gilteritinib narrowly missed the primary end point of relapse-free survival, with an HR of 0.679 but a P value of .0518. However, the benefit of gilteritinib varied by region and MRD status. Those with MRD tend to benefit from the drug, whereas the benefit is unclear for those without MRD. There was also greater separation of the survival curves between the arms in North American patients vs those in Europe and especially in Asia.

“Yes, the study did not meet its primary end point, but I think this was a successful study,” Levis opined. “We learned how to use the drug and in whom.… [Gilterinib] should be standard of care for those who are MRD positive.”

Also presenting findings relating to AML was the next speaker, Amir Fathi, MD, of Massachusetts General Hospital in Boston. He showed data on the menin inhibitor ziftomenib in adults with relapsed/refractory NPM1-mutated AML, noting that there is no currently approved treatment targeting this mutation. Focusing on the phase 1b expansion of the KOMET phase 1/2 study of ziftomenib in a heavily pretreated and heavily co-mutated patient population, Fathi discussed the activity and tolerability of the agent.

No new safety signals were observed, with the most common being nausea and differentiation syndrome, and there was encouraging clinical activity, with about one-third of participants achieving complete remission and a 45% overall response rate.

Not for the first time in data readouts at EHA 2023, the findings included a patient who was showing a promising response to treatment but then died of COVID-19 infection, offering a somber reminder of the pandemic’s lasting impact on scientific research.

“Resistance mutations have developed infrequently, and ziftomenib retains activity against common menin gatekeeper mutations,” Fathi said. He mentioned that the phase 1 KOMET-007 study is open for enrollment and will study ziftomenib in combination with chemotherapy in patients with newly diagnosed or relapsed AML who have certain mutations.

Pivoting away from leukemia, Jun Ho Jang, MD, PhD, of Samsung Medical Center in Seoul, Republic of Korea, delivered data on cevidoplenib, a novel selective inhibitor of spleen tyrosine kinase, in persistent and chronic immune thrombocytopenia (ITP). Chronic ITP is an orphan disease with an unmet need for emerging therapies, so this phase 2 trial aimed to evaluate its performance on an end point of increasing platelet count past 30,000 per μL and doubling platelet count from baseline.

Cevidoplenib was associated with a numerically greater rate of platelet response vs placebo (400 mg: 63.6%; 200 mg: 46.2%; placebo: 33.3%), but the difference was not statistically significant for either dose. Patients who sustained their platelet count, defined as having counts above 50,000 per μL at 4 or more of their last 6 visits, made up 27.3% of the 400 mg arm and 19.2% of the 200 mg arm; no patients in the placebo arm achieved this outcome.

“The results of the study warrant further clinical studies in a larger number of participants for an extended period to confirm durability of the clinical benefits,” Jang said.

Finally, Jens Panse, MD, of the University of Aachen in Germany, presented interim findings from a proof-of-concept trial of OMS906, a MASP-3 inhibitor, to normalize hemoglobin levels in patients with paroxysmal nocturnal hemoglobinuria (PNH). PNH is a rare and life-threatening disease that can lead to fatigue, anemia, and thrombosis, and there is an unmet need for novel complement inhibitors. After another investigation found OMS906 to be well tolerated in healthy patients, this study looked at 10 treatment-naïve patients with PNH.

In terms of safety, it appeared to be well tolerated, with 2 patients reporting headache and 3 reporting itching, but there were no major TEAEs. Its efficacy also appeared promising, as all patients without myelodysplastic syndrome reached hemoglobin levels considered normal for their gender.

“OMS906 dose escalation guided by the [pharmacokinetics and pharmacodynamics] of patients experiencing subclinical hemolysis is underway to inform achievement of quarterly dosing,” Panse said. He closed his presentation by giving special thanks to the patients and health care professionals in Ukraine who participated in this study, notably lead investigator Oksana Karnabeda, MD, of Bogomolets National Medical University of Kyiv.

In response to a question from session cochair Brian Huntly, MB ChB, PhD, of the University of Cambridge in England, Panse speculated that if these findings are confirmed in larger trials, “we might be able to achieve sustained complement inhibition by giving 4 subcutaneous doses per year, which might lead to very valuable options for patients if they have the choice of all; I’m always reminded that 80% of the world does not have access to any complement inhibitor.”