Early Signs of Activity Observed for Tagraxofusp Plus Decitabine in MDS, CMML

Tagraxofusp plus decitabine showed early evidence of clinical activity in myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML), reported Mehmet Sevki Uyanik, MD, at the 66th American Society of Hematology Annual Meeting & Exposition.

The phase I/II dose escalation study included nine patients (median age, 75 years; range, 59–83) diagnosed with high-risk MDS (n=5) or CMML (n=4) with prior hypomethylating agent treatment. Tagraxofusp was administered on days one through three of each cycle at a dose level of either 5 µg/kg (n=6) or 7 µg/kg (n=3) per day.

The median number of days to cycle 2 was 34 (range, 31–70), the median number of cycles administered was one (range, 1–6), and the median number of cycles to best response was two (range, 1–3). In seven patients who were evaluable at the time of analysis, three showed a response to tagraxofusp plus decitabine; two of these were complete responses.

Over a median follow-up of 5.3 months (range, 0–22; 95% CI, 2.1-8.6), the median overall survival was 9.4 months (95% CI, 5.4-11.4) and was comparable between patients with MDS and those with CMML at 8.4 months versus 6.6 months, respectively (P=.757). The median event-free survival for all patients was 4.1 months (95% CI, 0.5-7.7), and there were no significant differences between the MDS and CMML groups (P=.472).

According to the authors, the most common grade 1-2 treatment-emergent adverse events included fluid retention, diarrhea, constipation, and cough across all three patients. Febrile neutropenia, atrial fibrillation, and pneumonia were each observed in one patient.

Two patients older than 75 years experienced grade 3 capillary leak syndrome with concurrent grade 2 cytokine release syndrome. Both cases occurred in cycle 1 and reverted to baseline after management including steroids, albumin, and furosemide. One of the patients received a single dose of tocilizumab.

“Initial results of this phase I/II study suggest that the combination of TAG [tagraxofusp] with decitabine has early signs of clinical activity in both MDS and CMML,” Dr. Uyanik and colleagues concluded.

Reference

Uyanik MS, Garcia-Manero G, Maiti Abhishek, et al. Results of a phase I/II study of tagraxofusp in combination with decitabine for patients with myelodysplastic/myeloproliferative neoplasms and higher risk myelodysplastic syndromes. Abstract #1842. Presented at the 66th American Society of Hematology Annual Meeting & Exposition. December 7-10, 2024; San Diego, California.