Monotherapy with tagraxofusp showed promise in patients with relapsed or refractory myelofibrosis who were previously treated with JAK inhibitors, according to findings presented at the ASH 2021 Annual Meeting.

“Myelofibrosis is a myeloproliferative neoplasm characterized by splenomegaly, constitutional symptoms, bone marrow fibrosis and a propensity toward transformation to acute myeloid leukemia,” Abdulraheem Yacoub, MD, of University of Kansas Cancer Center, Westwood, Kansas, and colleagues wrote in an abstract. “Type I JAK inhibitors are the only approved therapy and can provide symptom control and reduction of splenomegaly in eligible patients. However, JAK inhibitors do not significantly impact disease progression, and many patients are not eligible due to coexisting cytopenias.”

The researchers performed a multicenter phase 1/2 trial of tagraxofusp, a first-in-class CD123-targeted therapy, upon 39 patients with relapsed or refractory myelofibrosis.

In stage 1, patients receive tagraxofusp intravenously at doses of 7, 9 or 12 mcg/kg per day on days 1 through 3 every 21 days for the first four cycles; followed by every 28 days in cycles 5, 6 and 7; and every 42 days for cycles 8 and any further cycles. In stage 2, patients received 12 mcg/kg per day every 21 days for the first four cycles, followed by every 28 days for cycle 5 and beyond. Only patients classified as intermediate-2 or high-risk, were intolerant of JAK inhibitors and not eligible for stem cell transplantation proceeded on to stage 2.

Thirty-nine patients underwent treatment, 46% of whom were female. The median age was 70 years. At baseline, patients had monocytosis, thrombocytopenia and splenomegaly.

Twenty-one patients (60%) achieved stable disease, the researchers reported. Of 24 patients with splenomegaly at baseline, half experienced a spleen response, including three out of four patients with concomitant monocytosis and 13 of 24 patients with concomitant thrombocytopenia, Yacoub and colleagues wrote.

The researchers confirmed spleen responses by using imaging and set 35% spleen volume reduction as the threshold for response. In the abstract, they added that updated information regarding reduction of spleen volumes would be discussed during their presentation.

Twenty of 39 patients (51%) experienced reductions in their total symptom scores and 26% achieved reductions in both baseline total symptom scores and spleen size, the researchers wrote.

The median OS was 29.2 months (95% CI, 12-49.5; range, 1-51 months), according to Yacoub and colleagues. The most common treatment-related adverse events were thrombocytopenia, pyrexia, headache and elevated alanine aminotransferase (15% each), as well as hypoalbuminemia (21%). Three patients experienced capillary leak syndrome, with the most severe occurring in one patient at grade 4.

“Tagraxofusp monotherapy demonstrated clinical efficacy and a predictable and manageable safety profile in patients with myelofibrosis characterized as high-risk, including those who are refractory to JAK inhibitors and those with associated monocytosis, thrombocytopenia, advanced disease, and high-risk genetic features,” Yacoub and colleagues wrote. “This phase 1/2 study confirms the safety and clinical efficacy of tagraxofusp administered as a monotherapy in a cohort of poor-prognosis patients with myelofibrosis.”

Disclosures: Yacoub reports membership on the board of directors or advisory committee of Acceleron Pharma, Agios, CTI Biopharma and Novartis; and a speaking role with Incyte. See the abstract for all authors’ financial disclosures.