Tagraxofusp, a CD123-targeted therapy, for chronic myelomonocytic leukemia: final results of a phase 1/2 study
Bibliographic record
Abstract
Chronic myelomonocytic leukemia (CMML) is an aggressive hematological neoplasm characterized by an expansion of CD123+ monocytes and plasmacytoid dendritic cells (pDC). PDC bone marrow clusters in CMML have been associated with higher rates of acute myeloid leukemia transformation. We evaluated tagraxofusp, a CD123-targeted therapy, in a phase 1/2 trial in patients with CMML. There were no dose-limiting toxicities. At the recommended phase 2 dose of 12 μg/kg/day, 37 patients were treated: 15 treatment-naïve; 22 with relapsed/refractory disease (median number of prior therapies: 1, range 1-7). Common nonhematologic treatment-emergent adverse events included fatigue (49%), hypoalbuminemia (46%), nausea, hypokalemia, and decreased appetite (44% each). Capillary leak syndrome occurred in nine patients (23%; grade 3-4, 13%), while tumor lysis syndrome was seen in 13%. Hematologic grade 3-4 treatment-related AEs included thrombocytopenia (28%), anemia (13%), leukocytosis (15%), and neutropenia (13%). No complete or partial responses were observed. One patient each in the treatment-naïve and relapsed/refractory groups achieved complete cytogenetic remission with marrow response. Stable disease and clinical benefit were achieved by 40% and 27% of treatment-naïve patients and by 59% and 23% of relapsed/refractory patients, respectively. After a median follow-up of 43.7 months, overall survival was 11.2 months in treatment-naïve and 15.6 months in relapsed/refractory patients. Exploratory analysis showed stable CD123+ blast frequency, mutational variant allele frequencies, and monocyte subsets with treatment. Tagraxofusp demonstrated a manageable safety profile with limited clinical efficacy in CMML. ClinicalTrials.gov identifier: #NCT02268253.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".