A Novel Anti-CD22 Immunotoxin, Moxetumomab Pasudotox (HA22, CAT-8015): Activity in Pediatric Patients with Relapsed Acute Lymphoblastic Leukemia (ALL) After Allogeneic Hematopoietic Stem Cell Transplantation (SCT)
Bibliographic record
Abstract
Despite the curative potential of SCT for pediatric ALL, relapse remains the most frequent cause of treatment failure. Management of relapse after SCT is complicated by drug resistance, limited utility of DLI, treatment-related toxicities, and GVHD. Moxetumomab pasudotox (MP) is a recombinant anti-CD22 immunotoxin with properties that warrant evaluation in the peritransplant setting. Cytotoxicity is mediated by targeted inhibition of protein synthesis in CD22+ cells, an antigen expressed on most B-lineage ALL blasts, and no immune effector cells are required for activity. A pediatric phase I trial of MP is being conducted for CD22+ hematologic malignancies (ClinicalTrials.gov NCT00659425). Doses are administered at 5-40 μg/kg IV QODx6 every 21 days. An initial cohort (A) included 1 patient each at the first 3 dose levels followed by standard 3+3 dose escalation starting at 30 μg/kg. In an attempt to prevent capillary leak syndrome (CLS), an ongoing cohort (B) receives dexamethasone around MP doses. 23 patients have been treated to date. The most common drug-related adverse events (AEs) were mild, reversible increased weight, transaminase elevation, and hypoalbuminemia. Treatment was discontinued in 1 patient after dose 1 due to ALL-related complications. Dose-limiting CLS was observed in 2 patients in Cohort A (30 μg/kg; grade 3 and 4, deemed drug-related serious AEs) and in no patients in Cohort B. 1 patient treated at 40 μg/kg developed refractory hypercalcemia, that was possibly drug-related, and died of cardiac arrhythmia during central venous catheter placement. That dose level (5B) was expanded and is accruing. 12 of 23 patients had prior SCT for ALL. Time from SCT to relapse was 3-12 mos (median, 9) and from SCT to treatment with MP was 4-34 mos (median, 13). 9 of 12 patients who had previously undergone SCT were evaluable for response. 3 (33%) patients had complete responses (CR) and 4 (44%) had hematological activity (>50% blast reduction and/or improvement in neutrophil/platelet counts). 1 patient with a CR confirmed by flow cytometry proceeded to 2nd SCT. MP is active in relapsed pediatric ALL after SCT. Notably, 3 of 4 CRs observed so far on this trial have been in patients treated for post-transplant relapse. The observed antileukemic activity and safety profile of MP, coupled with its unique properties, warrant further study in the peritransplant setting.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".