Pegaspargase
| Evidence Level: L1 | Predicted Indications: 10 |
Table of Contents
- Pegaspargase
- Pegaspargase: From Acute Lymphoblastic Leukemia to Precursor Lymphoblastic Lymphoma/Leukemia
Pegaspargase: From Acute Lymphoblastic Leukemia to Precursor Lymphoblastic Lymphoma/Leukemia
One-Sentence Summary
Pegaspargase is a long-acting, pegylated form of L-asparaginase, originally used as part of multi-agent chemotherapy for acute lymphoblastic leukemia (ALL). The TxGNN model predicts it may be effective for precursor lymphoblastic lymphoma/leukemia, a disease that is essentially the same as its original indication, so this is not a true repurposing case. Support is strong: 36 clinical trials and 19 publications are linked to this prediction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Acute lymphoblastic leukemia (the approved indication text is not listed in the US license record; the original indication is taken from the knowledge-graph indication data) |
| Predicted New Indication | Precursor lymphoblastic lymphoma/leukemia |
| TxGNN Prediction Score | 99.96% |
| Evidence Level | L1 |
| US Market Status | Cancelled only (the single BLA is cancelled) |
| Number of NDAs | 1 (BLA103411) |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known pharmacology, pegaspargase is a pegylated E. coli-derived L-asparaginase. It depletes circulating asparagine. Lymphoblasts have low asparagine synthetase expression and depend on external asparagine, so depletion selectively kills them. This mechanism is well established.
The predicted disease, precursor lymphoblastic lymphoma/leukemia, is the same malignant lymphoid lineage as the original indication, ALL. Lymphoblastic lymphoma and ALL are treated with the same asparaginase-containing regimens, such as BFM-type and hyper-CVAD protocols. The prediction therefore mostly confirms an existing use.
Other predictions in the data (such as chronic lymphocytic leukemia, follicular lymphoma and methylcobalamin deficiency cblE) have no trials or literature and a weak mechanistic rationale. They are not covered in detail here. One exception is extranodal NK/T-cell lymphoma, which has promising Phase 2 and retrospective data for pegaspargase-based regimens. It was mapped under “Hodgkin lymphoma” in the data and should be evaluated as a separate indication.
Clinical Trial Evidence
Almost all trials test pegaspargase-containing regimens, and in many the randomized question concerns another agent. Selected most relevant trials:
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00905034 | Phase 2 | Completed | 37 | MOAD regimen (methotrexate, vincristine, pegylated asparaginase, dexamethasone) in salvage ALL |
| NCT00967057 | Phase 3 | Completed | 470 | ALLR3 international trial in relapsed/refractory ALL with pegaspargase-containing chemotherapy backbones |
| NCT00103285 | Phase 3 | Completed | 5377 | Combination chemotherapy regimens in standard-risk B-precursor ALL; asparaginase is a standard backbone component |
| NCT05602194 | Phase 3 | Active, not recruiting | 440 | Levocarnitine to prevent asparaginase-associated hepatotoxicity in adolescents and young adults |
| NCT02003222 | Phase 3 | Active, not recruiting | 488 | Blinatumomab added to chemotherapy in newly diagnosed BCR-ABL-negative B-ALL; pegaspargase is in the backbone |
| NCT03643276 | Phase 3 | Recruiting | 5000 | AIEOP-BFM ALL 2017 protocol for children and adolescents |
| NCT03914625 | Phase 3 | Active, not recruiting | 6720 | Blinatumomab with chemotherapy (including pegaspargase) in standard-risk B-ALL or localized B-LLy |
| NCT00890656 | Phase 2 | Completed | 90 | Augmented hyper-CVAD in salvage ALL or lymphoblastic lymphoma |
| NCT01005914 | Phase 2 | Terminated | 11 | PEG-asparaginase added to hyper-CVAD in newly diagnosed adult ALL |
| NCT06376721 | Phase 1/2 | Recruiting | 43 | Linperlisib, camrelizumab and pegaspargase in relapsed/refractory NK/T-cell lymphoma |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 37276451 | 2023 | Cohort | Blood Adv | GIMEMA LAL1913: pegaspargase added to a risk-oriented pediatric-inspired program in adults aged 18-65 with Ph-negative ALL |
| 35271306 | 2022 | RCT | J Clin Oncol | COG AALL1231: phase III bortezomib trial in newly diagnosed T-ALL and T-LL |
| 32813610 | 2020 | RCT | J Clin Oncol | COG AALL0434: phase III nelarabine trial in newly diagnosed T-ALL |
| 27114587 | 2016 | RCT | J Clin Oncol | COG AALL0232: dexamethasone and high-dose methotrexate improve outcome in high-risk B-ALL |
| 34228505 | 2021 | Trial | J Clin Oncol | DFCI 11-001: efficacy and toxicity of pegaspargase versus calaspargase pegol in childhood ALL |
| 31030380 | 2019 | Review | Drugs | Pegaspargase is indicated in the USA and EU for ALL as part of multi-agent chemotherapy in children and adults; longer circulation than native E. coli asparaginase |
| 40109190 | 2025 | Review | Haematologica | Expert panel consensus on recognizing, preventing and managing asparaginase adverse events in adult ALL |
| 40858769 | 2025 | Cohort | Ann Hematol | Pegaspargase tolerability in patients aged 55 or older treated on LAL1913 |
| 10696127 | 2000 | Report | Med Pediatr Oncol | Incidence of pegaspargase-induced pancreatitis |
| 27643446 | 2017 | Review | Leuk Lymphoma | Hypersensitivity reactions with intravenous versus intramuscular pegaspargase |
US Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| BLA103411 (cancelled) | ONCASPAR (Servier Pharmaceuticals LLC) | Injection, solution | Not listed in the data compiled for this report |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Enzyme-based antineoplastic (asparagine-depleting), used within conventional cytotoxic combination chemotherapy |
| Myelosuppression Risk | Please refer to the package insert warnings and precautions |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | Liver function, triglycerides, glucose, pancreatic enzymes, coagulation parameters and signs of hypersensitivity; asparaginase activity where available (based on the literature) |
| Handling Protection | Please refer to the package insert warnings and precautions |
Safety Considerations
- Key Warnings and Contraindications: Package insert warnings and contraindications were not available in the data compiled for this report. Please refer to the package insert.
- Toxicities described in the literature: hypersensitivity reactions, pancreatitis, hepatotoxicity, thrombosis, hypertriglyceridemia and hyperglycemia. Tolerability decreases with age and obesity, and dose capping and levocarnitine for hepatotoxicity are being studied.
- Drug Interactions: 100 interactions were found, and those displayed are all of moderate level. Examples include corticosteroids (hydrocortisone, dexamethasone, betamethasone, triamcinolone, budesonide), glucose-lowering agents (metformin, acarbose, canagliflozin, dapagliflozin, alogliptin, saxagliptin, dulaglutide, albiglutide, chlorpropamide), aspirin, bupropion, and antibiotics (doxycycline, tetracycline, clarithromycin). The glucose-lowering agent interactions are consistent with the reported hyperglycemia during pegaspargase therapy.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: The predicted indication is essentially the original one (ALL and lymphoblastic lymphoma). Multiple completed Phase 3 trials and a large body of literature support pegaspargase-containing regimens, so efficacy evidence is strong. The main concerns are known toxicities, missing label safety data, and the fact that the only US license (BLA103411) is cancelled.
To proceed, the following is needed:
- Package insert warnings and contraindications (a blocking gap for safety screening)
- Mechanism of action data from DrugBank
- Verification of current US product availability and licensing status
- A monitoring plan for hypersensitivity, pancreatitis, hepatotoxicity, thrombosis and hypertriglyceridemia, with age-adjusted dosing
- Separate evaluation of extranodal NK/T-cell lymphoma as its own indication; the other predicted diseases (CLL, follicular lymphoma, cblE deficiency, CML blast phase) lack supporting evidence and should remain on hold
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.