Exploring New Settings for Tagraxofusp: CMML and Myelofibrosis

In late 2018, the U.S. Food and Drug Administration approved tagraxofusp-erzs for the treatment of adults and children with blastic plasmacytoid dendritic cell neoplasm, marking the first approval for this rare disease. At the 2019 American Society of Clinical Oncology Annual Meeting, researchers presented findings from two analyses from a study evaluating the CD123-targeted therapy in other myeloproliferative neoplasms: chronic myelomonocytic leukemia (CMML) and myelofibrosis.1,2


In the first study, Mrinal Patnaik, MBBS, from the Mayo Clinic in Rochester, Minnesota, and co-authors reported results from a phase I/II trial evaluating the optimal dose, safety, and efficacy of tagraxofusp in 23 patients with relapsed/refractory CMML (median age = 69 years; range = 43-80 years).

During the dose-escalation stage, tagraxofusp was administered intravenously in daily doses of 7 µg/kg, 9 µg/kg, or 12 µg/kg on days 1-3 every 21 days (cycles 1-4), every 28 days (cycles 5-7), and every 42 days (cycle 8 or longer). The expansion stage, which is enrolling patients, involves administering tagraxofusp 12 µg/kg in the same dosing scheme.

Hypomethylating agents were the most commonly received prior therapy, and 52% of participants (n=12) had splenomegaly at baseline, ranging from 2 to 27 cm below the costal margin.

Treatment-related adverse events (TRAEs) in this cohort included hypoalbuminemia (35%), thrombocytopenia (30%), nausea (26%), vomiting (26%), and anemia (22%). Thrombocytopenia (30%) and anemia (17%) were the most common grade ≥3 TRAEs in this population. Capillary leak syndrome of grade 2 in severity was observed in three patients (15%). “There were no apparent cumulative AEs, including in the bone marrow, over multiple cycles,” they added.

Among patients with splenomegaly at baseline, all 12 had a spleen response: Eight (67%) experienced reductions ≥50%, including half of the eight patients who had a baseline spleen size of ≥5 cm below the costal margin. In addition, three patients experienced a bone marrow complete response, including one who was successfully bridged to transplant.

“While the findings weren’t necessarily surprising, I would say they were definitely encouraging,” Dr. Patnaik told ASH Clinical News. “In patients with CMML, many patients have an enlarged spleen, which can be problematic. There are very few medical modalities for patients with CMML, so to have a drug that can produce such an impressive rate of spleen size reductions is very exciting.”

Dr. Patnaik added that further research is needed to confirm these results, which are limited by the small patient population and lack of a comparator arm. The findings from this study, he added, may assist in the identification of patients who benefit from treatment with tagraxofusp and determining how patients are responding over a longer period of time.


Naveen Pemmaraju, MD, from the University of Texas MD Anderson Cancer Center, presented results from an analysis of tagraxofusp in a cohort of 27 patients with relapsed/refractory myelofibrosis (median age = 69 years; range = 54-81 years). Patients had received a median of three prior lines of therapy (range = 1-3), and most (n=19; 70%) had disease that was refractory to Janus kinase (JAK) inhibitors, the only approved therapy for myelofibrosis.

“One of novel aspects of this study was the fact that we were able to enroll and treat many patients with thrombocytopenia in the study,” he added. At baseline, the median platelet count was 59×109/L (range = 13-579×109/L), and two-thirds of patients (n=18) had platelet counts ≤100×109/L.

Tagraxofusp was administered in the same regimen as in the CMML cohort. Again, tagraxofusp was associated with a “predictable and manageable safety profile,” the researchers noted. The most frequently reported TRAEs included increases in alanine aminotransferase (19%), headache (19%), hypoalbuminemia (19%), anemia (15%), and thrombocytopenia (15%). Four patients (15%) experienced grade ≥3 anemia, two (8%) experienced grade ≥3 anemia, and one (4%) experienced grade 3 capillary leak syndrome.

Of the 17 patients who had baseline spleen size ≥5 cm below the costal margin, nine (53%) experienced a reduction in spleen size. This included seven patients (41%) who had ≥29% reductions and four (24%) who had a ≥45% reductions.

Dr. Pemmaraju also highlighted the efficacy of tagraxofusp in patients with myelofibrosis and monocytosis (>1×109/L), a feature that has been associated with rapid disease progression and short survival. All five evaluable patients with monocytosis and baseline splenomegaly experienced a reduction in spleen size.

He added that initial quality-of-life assessments “appear promising,” suggesting that tagraxofusp could alleviate myelofibrosis symptom burden. Follow-up is ongoing, and five patients have had a treatment duration longer than 12 months.

“It is too early to compare and contrast therapies [for CMML and myelofibrosis], including tagraxofusp, as more time and follow-up is needed for all of these phase I and II studies, and most of these are not directly studied head to head,” Dr. Pemmaraju said, noting some limitations of these analyses.

The study authors reported relationships with Stemline Therapeutics, the manufacturers of tagraxofusp.


  1. Patnaik MM, Ali H, Gupta V, et al. Results from ongoing phase 1/2 clinical trial of tagraxofusp (SL-401) in patients with relapsed/refractory chronic myelomonocytic leukemia (CMML). Abstract #7059. Presented at the 2019 American Society of Clinical Oncology Annual Meeting, June 3, 2019; Chicago, Illinois.
  2. Pemmaraju N, Ali H, Gupta V, et al. Results from ongoing phase 1/2 clinical trial of tagraxofusp (SL-401) in patients with intermediate or high risk relapsed/refractory myelofibrosis. Abstract #7058. Presented at the 2019 American Society of Clinical Oncology Annual Meeting, June 3, 2019; Chicago, Illinois.