https://orcid.org/0000-0001-5293-4620
Key Points
In patients with myelofibrosis, tagraxofusp monotherapy was well tolerated with a manageable and predictable safety profile.
With modest clinical activity in patients with myelofibrosis, tagraxofusp warrants further investigation, including in combinations.
Abstract
Patients with myelofibrosis (MF) who are resistant to or relapse after JAK inhibitor therapy have limited treatment options and typically poor prognoses. CD123 is overexpressed in various myeloid malignancies, including MF. Tagraxofusp is a first-in-class CD123-targeted therapy and the only drug approved globally for the rare myeloid malignancy blastic plasmacytoid dendritic cell neoplasm. We conducted a phase1/2 trial to determine optimal dosing and evaluate safety and efficacy of tagraxofusp monotherapy in treatment-naïve (n=5) MF and patients with MF resistant/refractory to JAK inhibitors (n=25) and not eligible for stem cell transplant. There were no dose-limiting toxicities. The recommended phase 2 dose of tagraxofusp was 12 μg/kg/day for three consecutive days per cycle. In the safety population (n=36) treated at 12 μg/kg/day, the most frequent grade ≥3 treatment-emergent adverse events were thrombocytopenia (19%), anemia (22%), and dyspnea (11%). Capillary leak syndrome occurred in 11% of patients, all during cycle 1 with resolution in all patients. Thirty patients treated at 12 μg/kg/day were efficacy evaluable. Of 18 (n=2 treatment-naïve, n=16 relapsed/refractory) patients with baseline splenomegaly, two RR patients had SVR ≥35%. In relapsed/refractory patients, 40% had Total Symptom Score (TSS) ≥50%, and median overall survival (OS) was 19.3 months. In treatment-naïve patients, 40% had TTS ≥50%, and median OS was 26.6 months. In this trial, tagraxofusp monotherapy in MF was well tolerated, without cumulative myelotoxicity, and with symptom score improvements, warranting further investigation in combination therapy. This trial was registered at www.ClincalTrials.gov as #NCT02268253.
Author notes
A.Y. and H.A. are co-lead authors and contributed equally.
Data sharing statement: The data that support the results of this study may be requested for products and the relevant indications that have been authorized by the regulatory authorities in Europe/the United States (or, if not, two years have elapsed since the study completion). The Menarini Group will review requests individually to determine whether (1) the requests are legitimate and relevant and meet sound scientific research principles, (2) the requests are within the scope of the participants’ informed consent, and (3) the request is compliant with any applicable law and regulation and with any contractual relationship that Menarini Group and its affiliates and partners have in place with respect to the study and/or the relevant product. Prior to making data available, requestors will be required to agree in writing to certain obligations, including without limitation, compliance with applicable privacy and other laws and regulations. Proposals should be directed to medicalinformation@menarinistemline.com.
