2025-09-22
CMML: finally a target in sight?
Oncology
By Ana Espino | Published on september 22, 2025 | 3 min read
#Leukemia #CMML #CD123 #Tagraxofusp
Chronic myelomonocytic leukemia (CMML) is a rare and aggressive malignant blood disorder, characterized by clonal proliferation of monocytes and marked clinical heterogeneity. It mainly affects older individuals, carries a high risk of transformation into acute myeloid leukemia, and remains associated with limited median survival.
Current treatments, mainly based on hypomethylating agents such as azacitidine or decitabine, induce only partial and temporary responses, without significantly altering the natural history of the disease. To date, no targeted therapy has been approved for this indication, despite improved understanding of molecular profiles. A major challenge in the management of this condition therefore lies in developing innovative therapeutic strategies capable of selectively targeting leukemic cells without impairing normal hematopoiesis. Among the avenues being explored, CD123, which is overexpressed in most CMML cases, represents a promising target.
With this in mind, a study was launched to evaluate the efficacy and tolerability of tagraxofusp, a CD123-targeting immunotoxin, in patients with CMML.
Fourteen patients with CMML were enrolled in this study, selected according to their exposure to tagraxofusp (monotherapy at the standard dose of 12 mcg/kg/day for 5 days). Most had advanced disease, with prior treatments in 71% of cases, reflecting a heavily pretreated population.
Clinically, the responses observed included a reduction in circulating monocytes, stabilization of hematologic parameters, and, in some patients, partial improvement in the overall response score. Two patients showed a significant decrease in bone marrow infiltration, while another achieved a partial complete remission, indicating notable antitumor activity in some cases.
The tolerability profile was generally acceptable. As expected, hepatic toxicities and episodes of capillary leak syndrome were reported in some patients, but without major complications. These results suggest interesting therapeutic potential for tagraxofusp in this indication, which still lacks validated targeted options.
CMML is a rare and aggressive blood disorder, and its management remains particularly challenging after failure of hypomethylating agents. The main therapeutic hurdle is the lack of effective targeted treatments, despite the identification of relevant molecular targets.
In this context, this study aimed to evaluate the benefit of tagraxofusp, a CD123-targeting immunotoxin, in a population of heavily pretreated patients. The results suggest moderate antileukemic activity and overall acceptable tolerability, with clinical responses observed in some patients.
However, this study has several limitations, including the small sample size, lack of a comparison group, and a follow-up period too short to draw definitive conclusions. Larger, controlled trials—especially those combining tagraxofusp with standard treatments such as azacitidine—are needed. Targeting CD123 remains a promising approach, particularly in the setting of combined and personalized strategies for this disease, which still has no validated targeted therapy.
About the author – Ana Espino
As a scientific writer, Ana is passionate about bridging the gap between research and real-world impact. With expertise in immunology, virology, oncology, and clinical studies, she makes complex science clear and accessible. Her mission: to accelerate knowledge sharing and empower evidence-based decisions through impactful communication.
#Leukemia #CMML #CD123 #Tagraxofusp
Chronic myelomonocytic leukemia (CMML) is a rare and aggressive malignant blood disorder, characterized by clonal proliferation of monocytes and marked clinical heterogeneity. It mainly affects older individuals, carries a high risk of transformation into acute myeloid leukemia, and remains associated with limited median survival.
Current treatments, mainly based on hypomethylating agents such as azacitidine or decitabine, induce only partial and temporary responses, without significantly altering the natural history of the disease. To date, no targeted therapy has been approved for this indication, despite improved understanding of molecular profiles. A major challenge in the management of this condition therefore lies in developing innovative therapeutic strategies capable of selectively targeting leukemic cells without impairing normal hematopoiesis. Among the avenues being explored, CD123, which is overexpressed in most CMML cases, represents a promising target.
With this in mind, a study was launched to evaluate the efficacy and tolerability of tagraxofusp, a CD123-targeting immunotoxin, in patients with CMML.
Tagraxofusp: promise or just a threshold effect?
Fourteen patients with CMML were enrolled in this study, selected according to their exposure to tagraxofusp (monotherapy at the standard dose of 12 mcg/kg/day for 5 days). Most had advanced disease, with prior treatments in 71% of cases, reflecting a heavily pretreated population.
Clinically, the responses observed included a reduction in circulating monocytes, stabilization of hematologic parameters, and, in some patients, partial improvement in the overall response score. Two patients showed a significant decrease in bone marrow infiltration, while another achieved a partial complete remission, indicating notable antitumor activity in some cases.
The tolerability profile was generally acceptable. As expected, hepatic toxicities and episodes of capillary leak syndrome were reported in some patients, but without major complications. These results suggest interesting therapeutic potential for tagraxofusp in this indication, which still lacks validated targeted options.
CD123 opens the path to targeted therapy in CMML
CMML is a rare and aggressive blood disorder, and its management remains particularly challenging after failure of hypomethylating agents. The main therapeutic hurdle is the lack of effective targeted treatments, despite the identification of relevant molecular targets.
In this context, this study aimed to evaluate the benefit of tagraxofusp, a CD123-targeting immunotoxin, in a population of heavily pretreated patients. The results suggest moderate antileukemic activity and overall acceptable tolerability, with clinical responses observed in some patients.
However, this study has several limitations, including the small sample size, lack of a comparison group, and a follow-up period too short to draw definitive conclusions. Larger, controlled trials—especially those combining tagraxofusp with standard treatments such as azacitidine—are needed. Targeting CD123 remains a promising approach, particularly in the setting of combined and personalized strategies for this disease, which still has no validated targeted therapy.
Read next: ALL & acute abdomen: the silent alarm?
About the author – Ana Espino
PhD in Immunology, specialized in Virology
Last press reviews
Can we really predict relapse after breast surgery?
By Ana Espino | Published on october 3rd, 2025 | 3 min read
By Ana Espino | Published on october 1st, 2025 | 3 min read<br><br>...