Rylaze (asparaginase erwinia chrysanthemi (recombinant)-rywn) / Jazz, Ligand - LARVOL DELTA

Hypersensitivity to PEG-Asparaginase and Desensitization Strategies in Pediatric Acute Lymphoblastic Leukemia: A Narrative Review. (PubMed, Acta Med Acad) - "Recombinant Erwinia asparaginase (crisantaspase) is now licensed in the United States (2021) and the European Union (2023) for hypersensitive patients; however, cost, reimbursement, and local availability continue to limit access in many settings...Conclusion. A personalized, multidisciplinary approach-integrating TDM, realistic assessment of access to alternative formulations, and (where available) genetic data-is recommended to optimize treatment safety and antileukemic efficacy."

Journal • Acute Lymphocytic Leukemia • Allergy • Hematological Malignancies • Immunology • Leukemia • Oncology • Pediatrics • CNOT3 • GRIA1

Efficacy and safety of intramuscular (IM) recombinant Erwinia asparaginase in acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL): The Children’s Oncology Group (COG) AALL1931 study. (ASCO 2022) - P2/3 | "The totality of the results from AALL1931 demonstrate the positive benefit-risk profile of the IM JZP458 dosing regimen of 25 mg/m2 M/W and 50 mg/m2 F with a safety profile consistent with other asparaginases."

Clinical • Acute Lymphocytic Leukemia • Allergy • Hematological Malignancies • Immunology • Leukemia • Lymphoma • Oncology • Pancreatitis

Response-Based Chemotherapy in Treating Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome in Younger Patients With Down Syndrome (clinicaltrials.gov) - P3 | N=280 | Active, not recruiting | Sponsor: Children's Oncology Group | Trial completion date: Jun 2026 ➔ Jun 2027

Trial completion date • Acute Myelogenous Leukemia • Developmental Disorders • Genetic Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology • GATA1

Large Single Center Respective Study - Asparaginase Induced Hyperammonemia (SSIEM 2026) - "This was a retrospective study of patients who received at least one dose of an asparaginase product (Erwinaze®, Rylaze®, Oncaspar®, or Asparlas®) and a documented ammonia level from January 1, 2015 to December 31, 2025 at Ann & Robert H. Lurie Children's Hospital of Chicago. Our study showed that a relatively small percentage of patients receiving asparaginase products experienced hyperammonemia and hyperammonemic crises. Establishing awareness for identifying patients with symptoms of hyperammonemia, implementing a standardized protocol for monitoring ammonia levels post asparaginase injections and infusions and tailoring metabolic management are important aspects for mitigating serious acute and chronic outcomes associated with asparaginase products."

Clinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia

A PRECISION MEDICINE RANDOMIZED TRIAL FOR PATIENTS WITH RELAPSED OR REFRACTORY T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA BASED ON A FUNCTIONAL APPROACH. ALL-TARGET TRIAL (clinicaltrialsregister.eu) - P1/2 | N=12 | Not yet recruiting | Sponsor: Centre Hospitalier De Versailles

New P1/2 trial • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma

B-Cell All in a Jehovah's Witness Patient: Therapeutic Challenges and Clinical Considerations (ASPHO 2026) - "Supportive measures include epoetin alfa, iron, folate, vitamin B12, romiplostim, and intermittent tranexamic acid, aminocaproic acid, and recombinant factor VIIa. On Day 15 of induction, after nearly two weeks of hemoglobin < 5 g/dL, she developed atrial fibrillation with RVR that spontaneously cardioverted, prompting omission of that day's daunorubicin. During consolidation, she again sustained severe anemia (hemoglobin < 5 g/dL for 26 days) and thrombocytopenia (platelets < 10 × 103/µL for 14 days), requiring cardiac monitoring and omission of six doses of Rylaze...Additional modifications included four blinatumomab cycles and dose-reducing doxorubicin during delayed intensification... Treating B-ALL without transfusions is extremely challenging, with no established guidelines and limited pediatric data. This case highlights the consequences of prolonged severe anemia, uncertainty around safe procedural thresholds, and need for individualized..."

Clinical • Acute Lymphocytic Leukemia • Atrial Fibrillation • Hematological Malignancies • Leukemia • Thrombocytopenia • DUX4

Impact of Dosing Interval Adherence on Pharmacokinetic Outcomes of Recombinant Erwinia Asparaginase in Pediatric Leukemia or Lymphoma. (PubMed, Pharmacotherapy) - "Overall, our findings support the importance of adhering closely to the United States Food and Drug Administration approved dosing schedule for R-ASP to ensure adequate asparaginase activity in pediatric patients with leukemia or lymphoma."

Journal • PK/PD data • Retrospective data • Acute Lymphocytic Leukemia • Hematological Malignancies • Immunology • Leukemia • Lymphoma • Oncology • Pediatrics

ALL-TARGET: A Precision Medicine Trial for Patients With Relapsed or Refractory T Cell ALL (clinicaltrials.gov) - P2 | N=93 | Not yet recruiting | Sponsor: Philippe ROUSSELOT

New P2 trial • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma

Recombinant Erwinia Asparaginase and Venetoclax in Combination With Blinatumomab for the Treatment of Relapsed or Refractory CD19 Positive B-cell Acute Lymphoblastic Leukemia (clinicaltrials.gov) - P1 | N=26 | Recruiting | Sponsor: City of Hope Medical Center | Not yet recruiting ➔ Recruiting | Trial completion date: May 2027 ➔ Jun 2028 | Trial primary completion date: May 2027 ➔ Jun 2028

Enrollment open • Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

CR02: A Pilot Study to Establish Incidence and Characteristics of Patients at risk for Symptomatic Hyperammonemia Secondary to Recombinant Erwinia Asparaginase (HOPA 2026) - "Based on our small cohort, symptomatic hyperammonemia may be a common adverse effect for patients receiving recombinant Erwinia asparaginase. Checking plasma ammonia levels appears reasonable in patients who are experiencing nausea and vomiting."

Clinical • Acute Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Lymphoma

Pilot Study to Establish Incidence and Characteristics of Patients at Risk for Symptomatic Hyperammonemia Secondary to Recombinant Erwinia Asparaginase (HOPA 2026) - "Based on our small cohort, symptomatic hyperammonemia may be a common adverse event for patients receiving recombinant Erwinia asparaginase. Checking plasma ammonia levels is reasonable in patients who have nausea and vomiting."

Clinical • Acute Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Lymphoblastic Lymphoma • Lymphoma

Asparaginase Erwinia Chrysanthemi With Chemotherapy for the Treatment of High-Risk Adults With Newly Diagnosed Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma (clinicaltrials.gov) - P2 | N=53 | Recruiting | Sponsor: City of Hope Medical Center | Suspended ➔ Recruiting

Enrollment open • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Pediatrics • CD20

Asparaginase Erwinia Chrysanthemi With Chemotherapy for the Treatment of High-Risk Adults With Newly Diagnosed Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma (clinicaltrials.gov) - P2 | N=53 | Suspended | Sponsor: City of Hope Medical Center | Recruiting ➔ Suspended

Trial suspension • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Pediatrics • CD20

Recombinant Erwinia Asparaginase and Venetoclax in Combination With Blinatumomab for the Treatment of Relapsed or Refractory CD19 Positive B-cell Acute Lymphoblastic Leukemia (clinicaltrials.gov) - P1 | N=26 | Not yet recruiting | Sponsor: City of Hope Medical Center | Initiation date: Jan 2026 ➔ Jun 2026

Trial initiation date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

Etoposide, Prednisone, Vincristine, Cyclophosphamide, and Doxorubicin (DA-EPOCH) With or Without Rituximab Plus Recombinant Erwinia Asparaginase (JZP458) for the Treatment of Newly Diagnosed Ph Negative B-Acute Lymphoblastic Leukemia or T Acute Lymphoblastic Leukemia (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: University of Washington | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • T Acute Lymphoblastic Leukemia

AML16: A Trial of Epigenetic Priming in Patients With Newly Diagnosed Acute Myeloid Leukemia (clinicaltrials.gov) - P2 | N=206 | Active, not recruiting | Sponsor: St. Jude Children's Research Hospital | Trial primary completion date: Jun 2025 ➔ Sep 2025

Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

A phase 2 study evaluating the safety and efficacy of first line asparaginase recombinant erwinia asparaginase (Rylaze) during pediatric-inspired regimen in high-risk adults with newly diagnosed ALL or lbl (ASH 2025) - P2 | "Background and Significance: Pegaspargase-based therapy for acute lymphoblastic leukemia (ALL) offers well-established benefits but treatment-related toxicity precludes its widespread adoption. If our study demonstrates the tolerability and safety of using frontline recombinant Erwinia asparaginase during induction in high-risk adults with ALL, this approach could potentially establish it as the first-line asparaginase in this population and support its use in subsequent treatment cycles. Acknowledgements:This study is financially supported by Jazz Pharmaceuticals, which also conducted a courtesy medical review of this abstract."

Clinical • P2 data • Acute Lymphocytic Leukemia • Genetic Disorders • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Lymphoblastic Lymphoma • Lymphoma • Obesity • Pancreatitis • Pediatrics • Thrombosis

AAML1831: A Study to Compare Standard Chemotherapy to Therapy With CPX-351 and/or Gilteritinib for Patients With Newly Diagnosed AML With or Without FLT3 Mutations (clinicaltrials.gov) - P3 | N=1186 | Recruiting | Sponsor: Children's Oncology Group | Trial completion date: Sep 2027 ➔ Jun 2029 | Trial primary completion date: Sep 2027 ➔ Jun 2029

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3

AALL1621: Inotuzumab Ozogamicin in Treating Younger Patients With B-Lymphoblastic Lymphoma or Relapsed or Refractory CD22 Positive B Acute Lymphoblastic Leukemia (clinicaltrials.gov) - P2 | N=80 | Recruiting | Sponsor: Children's Oncology Group | Trial completion date: Mar 2026 ➔ Dec 2026 | Trial primary completion date: Mar 2026 ➔ Dec 2026

Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • CD22

A Single Center, 10-Year Experience of CALGB-10403 Regimen in AYA Population with Philadelphia-Chromosome Negative Acute Lymphoblastic Leukemia (ASH 2023) - "One of the patients with refractory disease underwent further therapy with blinatumomab, inotuzumab, CAR-T and allogeneic stem cell transplantation and is alive at 16 months from diagnosis...Noteworthy adverse effects include neutropenic fever (65%), liver function tests (LFT) abnormalities (70%), and neuropathy from vincristine (70%). Peg-asparaginase administration was associated with pancreatitis in 12%, thromboembolism in 30% and hypersensitivity reactions in 24% requiring switching to alternative forms of asparaginase products (erwinia and Rylaze)... The pediatric-inspired regimen CALGB 10403 was safe and efficacious in our AYA Ph- ALL population with no deaths due to treatment and a 5-year overall survival of 94%. Toxicities, especially from peg-asparaginase, should be closely monitored. While most patients will attain durable remission/cure, the minority with refractory or relapsed disease can still be successfully salvaged to achieve long term survival."

Clinical • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Malignancies • Immunology • Leukemia • Oncology • Pancreatitis • Pediatrics • T Acute Lymphoblastic Leukemia • Transplantation • KMT2A

Unveiling Putative Pathway Enrichment Following Crisantaspase Treatment in AML through RNA Sequencing Analysis (ASH 2023) - " We utilized Rylaze, an FDA-approved Erwinia crisantaspase, to deplete exogenous Gln. This study represents a significant contribution towards advancing our understanding of amino acid-regulated metabolic pathways in AML, with potential implications for other Gln metabolism-dependent cancers as well."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CHAC1 • S100P

UPDATE AML: UPdated Disease Monitoring And Treatment for Enhanced Outcomes for Pediatric AML (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: Joanna Yi | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics

Real-World Treatment Patterns Among Patients with Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic Lymphoma (LBL) Who Initiated an Asparaginase Treatment after the Approval of Recombinant Erwinia (Rylaze) (ASH 2023) - "Four asparaginase molecules were included in this study, 2 Erwinia-derived - recombinant Erwinia(Rylaze) and native Erwinia (Erwinaze), and 2 E. coli-derived - pegaspargase (Oncaspar) and calaspargase pegol-mknl (Asparlas). Limitations of this study included the nature of the database used, containing mostly outpatient data, and the relatively short study time frame. Future studies with additional data are needed to fully understand the real-world asparaginase use patterns in these patient populations."

Clinical • HEOR • Real-world • Real-world evidence • Acute Lymphocytic Leukemia • Chronic Obstructive Pulmonary Disease • Diabetes • Genetic Disorders • Hematological Malignancies • Hepatology • Immunology • Leukemia • Lymphoma • Metabolic Disorders • Obesity • Oncology • Pediatrics • Pulmonary Disease • Respiratory Diseases

Immunogenicity of Recombinant Erwinia asparaginase (JZP458) for Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic Lymphoma (LBL) (ASH 2023) - P2/3 | "Each dose of E. coli-derived pegaspargase was substituted with 6 doses of JZP458 either intramuscularly (IM, Part A) or intravenously (IV, Part B) on Mon/Wed/Fri over 2 weeks, defined as 1 course. The majority of pts who developed ADAs did not develop HSRs or NAbs. The overall rate of HSRs was similar to literature-reported rates for ASP and appeared to be higher with IV vs IM JZP458. ADA status did not appear to impact PK and other AEs for JZP458."

Acute Lymphocytic Leukemia • Hematological Malignancies • Immunology • Leukemia • Lymphoma • Oncology • Pediatrics

Efficacy and Safety of Recombinant Erwinia Asparaginase (JZP458) in Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic Lymphoma (LBL): Complete Follow-up of the Children's Oncology Group (COG) AALL1931 Study (ASH 2023) - P2/3 | " Eligible patients with ALL/LBL who developed hypersensitivity (grade ≥3 allergic reaction or silent inactivation) to E. coli-derived pegaspargase received JZP458 as part of their multi-agent treatment plan. Results at the completion of AALL1931 in patients with ALL/LBL and allergic reactions or silent inactivation to E. coli-derived asparaginase show the safety profile of JZP458 is consistent with other asparaginases, with no new adverse safety signals. Treatment-related discontinuation rates with IV JZP458 were greater than with IM, primarily due to increased incidence of hypersensitivity/infusion-related reactions along with nausea and vomiting; however, the study was not statistically powered to compare different dosing cohorts. Observed and PPK modeling data demonstrate JZP458 achieves therapeutic NSAA levels via multiple IM and IV dosing schedules, with IM dosing having more sustained SAA, and therefore providing flexibility to patients and physicians."

Clinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Immunology • Lymphoma • Pancreatitis • Pediatrics