Pegaspargase

Evidence Level: L5

Predicted Indications: 7

Pegaspargase

Pharmacist Assessment Report

Pegaspargase: Chronic lymphocytic leukemia/small lymphocytic lymphoma with immunoglobulin heavy chain variable-region gene somatic hypermutation

One-Sentence Summary

Pegaspargase is a PEGylated L-asparaginase originally used to treat acute lymphoblastic leukemia (ALL). The direction is supported by more than 30 registered clinical trials and 20 publications, including multiple completed Phase 3 trials of regimens that contain pegaspargase.

Quick Overview

Item	Content
Original Indication	Not recorded in the local data
Predicted New Indication	Chronic lymphocytic leukemia/small lymphocytic lymphoma with immunoglobulin heavy chain variable-region gene somatic hypermutation
TxGNN Prediction Score	0.9995
Evidence Level	L5
India Market Status	Listed in a compiled Indian medicine price dataset (2 of 2) – CDSCO approval status is not included in this data
Number of Listed Products	2 (valid: 2)
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available in the compiled data. From known pharmacology, pegaspargase is a PEGylated form of E. coli-derived L-asparaginase. It depletes circulating asparagine. Lymphoblasts have low asparagine synthetase expression and depend on external asparagine, so depletion selectively starves them.

The predicted indication is the labeled indication (ALL) under another name, so the mechanism applies directly. Pegaspargase is a standard component of multi-agent ALL and lymphoblastic lymphoma regimens, including pediatric-inspired adult protocols.

Clinical Trial Evidence

The table lists the most relevant trials. In most of them, pegaspargase is part of a combination regimen and its individual contribution is not isolated.

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00967057	Phase 3	Completed	470	ALLR3: relapsed/refractory ALL, regimen includes pegylated asparaginase
NCT00103285	Phase 3	Completed	5377	Combination chemotherapy in standard-risk B-precursor ALL; pegaspargase is part of the backbone
NCT02003222	Phase 3	Active, not recruiting	488	Blinatumomab added to chemotherapy in newly diagnosed B-ALL in adults; pegaspargase is in the backbone
NCT01190930	Phase 3	Completed	9350	Risk-adapted chemotherapy in standard-risk B-ALL or localized B-lymphoblastic lymphoma
NCT03643276	Phase 3	Recruiting	5000	AIEOP-BFM ALL 2017 protocol for children and adolescents with ALL
NCT05602194	Phase 3	Active, not recruiting	440	Levocarnitine to prevent asparaginase-associated hepatotoxicity (supportive care, not efficacy)
NCT00905034	Phase 2	Completed	37	MOAD regimen (methotrexate, vincristine, pegylated asparaginase, dexamethasone) in salvage ALL
NCT00890656	Phase 2	Completed	90	Augmented hyper-CVAD in salvage ALL; asparaginase involvement likely but not confirmed
NCT01005914	Phase 2	Terminated	11	PEG-asparaginase added to hyper-CVAD in newly diagnosed adult ALL
NCT01403415	Phase 1	Completed	13	Temsirolimus with re-induction chemotherapy including pegaspargase in relapsed pediatric ALL/NHL

Literature Evidence

PMID	Year	Type	Journal	Key Findings
35271306	2022	RCT	J Clin Oncol	COG AALL1231: bortezomib in newly diagnosed T-ALL and T-LL
32813610	2020	RCT	J Clin Oncol	COG AALL0434: nelarabine in newly diagnosed T-ALL
27114587	2016	RCT	J Clin Oncol	AALL0232: dexamethasone and high-dose methotrexate improve outcome in high-risk B-ALL
31030380	2019	Review	Drugs	Pegaspargase review in ALL: longer circulation time than native asparaginase and less frequent dosing
40109190	2025	Review	Haematologica	Expert consensus on managing asparaginase/pegaspargase adverse events in adults with ALL
37276451	2023	Cohort	Blood Adv	GIMEMA LAL1913: pegaspargase-modified risk-oriented program in adult ALL
34228505	2021	Clinical study	J Clin Oncol	DFCI 11-001: efficacy and toxicity of pegaspargase versus calaspargase pegol in childhood ALL
40858769	2025	Cohort	Ann Hematol	Tolerability of pegaspargase in patients aged 55 or older treated with LAL1913
27643446	2017	Review	Leuk Lymphoma	Hypersensitivity reactions with intravenous versus intramuscular pegaspargase
14499708	2003	Review	Adv Drug Deliv Rev	Review of pegaspargase clinical studies

India Market Information

Authorization Number	Product Name	Dosage Form	Approved Indication
5649	Asviia Injection (Zydus Cadila)	Vial of 5 ml injection	Not stated in registration records
104157	Hamsyl Injection (Emcure Pharmaceuticals Ltd)	Vial of 5 ml injection	Not stated in registration records

Cytotoxicity

Item	Content
Cytotoxicity Classification	Enzyme-based antineoplastic (asparagine depletion); not a conventional DNA-damaging cytotoxic agent
Myelosuppression Risk	Please refer to the package insert warnings and precautions
Emetogenicity Classification	Please refer to the package insert warnings and precautions
Monitoring Items	Literature points to monitoring for hepatotoxicity, pancreatitis, hypertriglyceridemia, hyperglycemia, thrombosis and hypersensitivity (liver function, lipids, glucose, amylase/lipase, coagulation)
Handling Protection	Please refer to the package insert warnings and precautions

Safety Considerations

Known toxicities (from the literature): hypersensitivity reactions, pancreatitis, hepatotoxicity, thrombosis, hypertriglyceridemia and hyperglycemia. Risk appears to rise with age and obesity in adults, and dose capping and levocarnitine have been studied to reduce hepatotoxicity.
Drug Interactions: 378 interactions were identified. All 20 listed in the data are Moderate. They include:
- corticosteroids (hydrocortisone, dexamethasone, betamethasone, triamcinolone, budesonide)
- antidiabetic agents (metformin, acarbose, alogliptin, albiglutide, canagliflozin, dapagliflozin, saxagliptin, dulaglutide, chlorpropamide)
- antibiotics (doxycycline, tetracycline, clarithromycin)
- others (bupropion, acetylsalicylic acid, chenodeoxycholic acid)
The glucose-lowering and corticosteroid interactions are relevant because pegaspargase and steroids can both cause hyperglycemia.

Label warnings and contraindications are not available in the compiled data. Please refer to the package insert for full safety information.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: The predicted indication is the established on-label use (ALL and lymphoblastic lymphoma), supported by several completed Phase 3 trials and RCT-level literature. Pegaspargase is part of standard regimens, but most trials do not isolate its individual effect, and its toxicity profile requires active management.

To proceed, the following is needed:

Package insert warnings and contraindications from the Indian registrations (currently missing, which blocks formal safety screening)
Approved indication text for the two Indian products
Detailed mechanism of action data from DrugBank
A toxicity monitoring plan covering hypersensitivity, pancreatitis, hepatotoxicity, thrombosis and metabolic effects, with age and obesity considerations for adults

Other predicted indications (not recommended at this time):

Lymphoid neoplasm (Proceed with Guardrails): the evidence comes almost entirely from ALL.
Hodgkin lymphoma (Hold): no direct evidence. The literature relates to extranodal NK/T-cell lymphoma, which is a separate disease with a plausible asparaginase rationale but needs its own evaluation.
CLL/SLL subtypes, follicular lymphoma, blast-phase CML, methylcobalamin deficiency cblE (Hold): prediction only or weak evidence, with no supporting mechanism or data.
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.