nelarabine / Generic mfg. - LARVOL DELTA

Oncogenetic-Driven Targeted Therapy for Relapsed/Refractory T-Cell Acute Lymphoblastic Leukemia : A French ALL-Target Observatory Report (ASH 2023) - P | "In relapse/refractory (R/R) patients, standard of care treatments, including nelarabine, yield response rate of about 20-40% and responses are of short duration...For example, TTOs included Tofacitinib and Venetoclax (Tofa/Ven) in case of IL7R (CD127) expression or IL7R-pathway alterations (IL7RALT), 5-azacytidine and Venetoclax (Aza/Ven) in case of T-ALL/LL with epigenetic regulators alterations (DNMT3A, ASXL1, PHF6, TET2, PRC2, IDH1/2, SRSF2...) or Temsirolimus, Erwinase and Venetoclax (Tem/Erw/Ven) in case of PI3K signaling pathway alterations (PI3KALT)...Twenty-five patients received a TTO, including 14 Aza/Ven (56%), 8 Tofa/Ven (32%), 2 Tem/Erw/Ven (8%) and 1 Trametinib/Ven (4%)...A better knowledge of the oncogenetic landscape of T-ALL, and a close collaboration between clinicians and biologists, resulted in individualized treatment strategies. With a 3 months cumulative incidence of response of 70%, TTOs appear to be a promising approach in R/R T-ALL."

IO biomarker • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • ASXL1 • ATM • BCL2 • DNMT3A • IDH1 • IDH2 • IL7R • PHF6 • SRSF2 • TET2 • TP53

Mini-hyper-CVD with venetoclax (Ven) for patients with relapsed/refractory (R/R) Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL): A phase II study. (ASCO 2023) - P1/2 | " Pts ≥18 years with R/R Ph-negative B- or T-cell ALL received mini-HCVD alternating with methotrexate and cytarabine for up to 8 cycles...Rituximab (if CD20+ B-ALL) and prophylactic IT chemotherapy x8 doses were given for the first 4 cycles. Pts with T-ALL received additional 2 cycles of nelarabine and peg-asparaginase during consolidation without Ven, and 2 cycles during maintenance. Maintenance with vincristine, prednisone and Ven was given for up to 2 years...Among the 18 B-ALL pts, 16 (89%) had received prior blinatumomab and 7 (39%) prior inotuzumab... The combination of low-intensity chemotherapy mini-HCVD with Ven in pts with R/R Ph-negative ALL was well-tolerated and resulted in a response rate of 67%. Further studies examining the role of Ven-based therapies in ALL are needed for newly diagnosed and R/R pts. Clinical trial information: NCT03808610."

Clinical • P2 data • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • Transplantation • CD20

Venetoclax Added to Hyper-CVADNelarabine and Pegylated Asparagine Improves Outcomes in Patients With T-Cell Acute Lymphoblastic Leukemia/ Lymphoma (SOHO 2024) - P2 | " The ongoing phase 2 clinical trial of hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, adriamycin, and dexamethasone alternating with methotrexate and cytarabine) with nelarabine and pegylated asparaginase (PegAsP) (NCT00501826) has shown promising response rates and survival in adult patients with T-ALL/LBL in the frontline settings (original cohort). Addition of venetoclax to hyper-CVAD-nelarabine-PegAsp is promising and tolerable in the frontline setting for adult patients with T-ALL/LBL."

Clinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • T Acute Lymphoblastic Leukemia

Risk-Adjusted Therapies Yield Equivalent Outcomes for Adolescents and Young Adults (AYAs) Treated for Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia (T-ALL) on Children's Oncology Group (COG) Studies AALL0434 and AALL1231 (ASH 2023) - "On AALL0434, participants were randomized to receive escalating dose methotrexate (CMTX) without leucovorin rescue + pegaspargase or high dose MTX (HDMTX) + leucovorin rescue. Intermediate and high-risk patients were randomized to receive or not receive six 5-day courses of nelarabine (Nel)...Key differences between AALL0434 and AALL1231 ABFM backbones included the use of prednisone in induction in AALL0434 versus dexamethasone in AALL1231, and cranial radiation therapy in the majority of AALL0434 participants versus only in patients with central nervous system involvement in AALL1231...Despite small numbers, CMTX holds a survival advantage for AYA T-ALL patients, with no survival disadvantage seen among AYA T-ALL patients who received Nel. Bortezomib does not offer significant benefit for AYA T-ALL patients."

Clinical • Acute Lymphocytic Leukemia • CNS Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • Respiratory Diseases • Septic Shock • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma

Longitudinal follow up of a phase 2 trial of venetoclax added to hyper-CVAD, nelarabine and pegylated asparaginase in patients with T-cell acute lymphoblastic leukemia and lymphoma. (PubMed, Leukemia) - "Febrile neutropenia was the most common serious adverse event, seen in 60% patients. The addition of venetoclax to HyperCVAD-nelarabine-pegylated asparaginase was tolerable and led to improvement in DOR and PFS."

Journal • P2 data • Acute Lymphocytic Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Neutropenia • Oncology • T Acute Lymphoblastic Leukemia

ENCERT: A Multisite Phase 1 Trial Using Everolimus in Combination With Nelarabine, Cyclophosphamide, and Etoposide in Relapsed T-Cell Lymphoblastic Leukemia/Lymphoma. (PubMed, Pediatr Blood Cancer) - P1 | "This study demonstrates safety with a combination of everolimus and NEC chemotherapy. Given the observed tolerability and efficacy of everolimus with NEC in this small cohort of patients, this combination should be further evaluated in larger phase 2/3 clinical trials."

Journal • P1 data • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Oncology • T Acute Lymphoblastic Leukemia • T Cell Non-Hodgkin Lymphoma • T-cell Acute Lymphoblastic Lymphoma • Transplantation

Healthcare Resource Use and Economic Burden of B-Cell Acute Lymphoblastic Leukemia for Patients in the United States (SOHO 2026) - "Exclusions were pre-index B-ALL therapy, clinical trial participation, hospice, refractory or relapsed B-ALL, other B-cell malignancies or acute myeloid leukaemia, and daratumumab or nelarabine at baseline...Therapy included chemotherapy/rituximab (88.1%), TKIs (35.2%), blinatumomab (18.0%), inotuzumab (4.6%), and CAR-T (0.23%)... Adult US-based patients with B-ALL experience substantial and sustained economic burden following treatment initiation, with higher HCRU and costs driven primarily by medication, particularly advanced targeted therapies. Quantified, medication-driven costs following initiation give payers and providers actionable inputs for budget forecasting, and establish benchmarks to support value assessments for advanced therapies. Future research should stratify by treatment line and clinical risk, incorporate episode-based cost attribution, and include outcomes-adjusted evaluations to inform value."

Clinical • HEOR • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

Nelarabine (NEL), Pegylated Asparginase (PEG) and Venetoclax (VEN) Incorporated to HCVAD Chemotherapy in the Frontline Treatment of Adult Patients with T-Cell Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma (T-ALL/T-LBL) (ASH 2023) - "Pts received 8 cycles (C) of HCVAD (C 1,3, 5, 7) alternating with high dose Ara-C and methotrexate (MTX) (C 2, 4, 6, 8) at approximately 3-week intervals...After the completion of the intensive phase; pts in all cohorts received 30 cycles of maintenance therapy with monthly POMP (prednisone, vincristine, MTX, prednisone) and early intensification with NEL/PEG on C6 and 7 and late intensification with MTX/PEG in C18 and HCVAD on C19... The ongoing phase 2 trial of NEL, ASP, VEN added to the HCVAD regimen shows promising long-term survival in adult pts with T-ALL/LBL with 3-yr OS of 76%-88% in pts treated with HCVAD+NEL+PEG +/- VEN. Larger prospective trials and longer follow-up are needed to demonstrate further benefit."

Clinical • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Pediatrics • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma

Frontline Consolidation with Nelarabine for Adults with High-Risk T-Cell Acute Lymphoblastic Leukemia. Results of the Graall-2014/T Atriall Phase 2 Study (ASH 2023) - "NELA was given at 1,500 mg/sqm/day at day 1,3 and 5 in combination with etoposide and cyclophosphamide for a maximum of 5 courses during consolidation (2 cycles) and maintenance (3 cycles). While NELA did not yield an overall improved outcome in the study population, benefits were observed in favorable MRD responders and non-ETP patients. Additional prospective studies are needed to further delineate the specific patient subgroups that might benefit from NELA."

Clinical • P2 data • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • Transplantation • FBXW7 • NOTCH1 • PTEN

A phase 1 study to evaluate the safety, pharmacology, and feasibility of continuous infusion nelarabine in patients with relapsed and/or refractory lymphoid malignancies. (PubMed, Cancer) - "Preliminary evaluation of continuous infusion schedule of nelarabine suggests that the safety profile is acceptable for this patient population, with clinical activity observed even at low doses and could broaden the use of nelarabine both as single agent and in combinations by potentially mitigating the risk of central nervous system toxicities."

Journal • P1 data • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Pain • Prolymphocytic Leukemia • T Acute Lymphoblastic Leukemia

ADVANCING CHEMOGENOMIC STRATEGIES FOR FUNCTIONAL PRECISION MEDICINE IN RELAPSED/REFRACTORY T-ALL AND ETP-ALL: PRELIMINARY RESULTS OF THE GIMEMA ALL2720 TRIAL (EHA 2025) - P=N/A | "In response to this unmet clinical need, we developed a chemogenomic platform aimed at identifying potential therapeutic alternatives to nelarabine, the only single agent currently approved for patients with relapsed or refractory (R/R) T-ALL... In conclusion, we suggest that a coordinated, unified platform can address the needs of large, densely populated countries by delivering functional genomic data to guide "on-time" therapeutic decisions. Our results indicate that nearly 40% of R/R T-ALL cases, especially ETP with unknown subtype-defining oncogenic lesions, can be rescued through a tandem DRP-alloHSCT, providing a long-term solution for this aggressive disease."

IO biomarker • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • BCL2 • CDKN2B • NOTCH1 • TLX1

Nelarabine-associated rhabdomyolysis with severe creatine kinase elevation in a pediatric patient with T-cell acute lymphoblastic leukemia: a case report. (PubMed, Front Oncol) - "Nelarabine was discontinued, and aggressive intravenous hydration led to complete clinical and biochemical recovery without acute kidney injury or renal replacement therapy. This case provides a detailed pediatric description of clinically overt nelarabine-associated rhabdomyolysis and emphasizes early recognition, renal-protective management, and CK monitoring in symptomatic patients."

Journal • Acute Kidney Injury • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Musculoskeletal Pain • Nephrology • Oncology • Pain • Pediatrics • Renal Disease • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • MB

Remission of B/T MPAL After T-ALL-Directed Chemotherapy and Transplantation: Insights From Genomic Analysis. (PubMed, Pediatr Int) - No abstract available

Journal • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • Transplantation

ADULT T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA: EPIDEMIOLOGICAL, CLINICO-BIOLOGICAL, AND THERAPEUTIC PROFILE (EHA 2026) - "Summary/Conclusion Our results were lower than those reported in the literature. Further research in molecular biology, combined with strict MRD monitoring as well as the use if nelarabine, is essential to improve therapeutic outcomes."

Clinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma

PREDICTIVE FACTORS OF RELAPSE IN ADULT T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA (EHA 2026) - "Among these patients, 13 received salvage therapy: high-dose cytarabine (HD Ara-C) : 5 patients, GRAALL05 reinduction : 3 patients, GRAALL14 reinduction : 2 patients, 2+5 regimen : 1 patient, hyper-CVAD : 1 patient, and high-dose methotrexate (HD MTX) : 1 patient...Summary/Conclusion Salvage treatment options remain very limited in our country. The use of therapeutic agents such as nelarabine and venetoclax has led to improved therapeutic outcomes and thus to better prognosis."

Biomarker • Clinical • Acute Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma

EFFICACY OF ANTI-RELAPSE TREATMENT PROGRAMS IN ADULT PATIENTS WITH BCR::ABL1-NEGATIVE ACUTE LYMPHOBLASTIC LEUKEMIA. (EHA 2026) - "As anti-relapse treatment programs, 15 patients with B-ALL received the following: blinatumomab -5, bortezomib-containing regimens - 3, inotuzumab ozogamicin - 1, anti-CD19 CAR-T - 2, no data for 4 patients; 15 patients with T-ALL: nelarabine-containing regimens - 5, hypomethylating agents with venetoclax — 5, no data for 5 patients. Fig 1. Three-year overall survival in adult patients with relapse BCR::ABL1-negative acute B-lymphoblastic leukemia and acute T-lymphoblastic leukemia"

Clinical • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Leukemia • T Acute Lymphoblastic Leukemia • ABL1

THE EFFICACY AND SAFETY OF NELARABINE IN RELAPSED OR REFRACTORY T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA: A SYSTEMATIC REVIEW AND META-ANALYSIS (EHA 2026) - "However, its use, both as monotherapy and in combination therapy, is associated with considerable adverse events, particularly neurotoxicity and hematologic toxicities, necessitating careful monitoring. Further research is needed to optimize its application across diverse patient populations and to better manage its associated toxicities."

Retrospective data • Review • Acute Lymphocytic Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • Thrombocytopenia

TENACITY-01 A GLOBAL STUDY OF CTD402, ALLOGENEIC ANTI-CD7 CAR T-CELL, IN RELAPSED OR REFRACTORY (R/R) T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA/LYMPHOBLASTIC LYMPHOMA (T-ALL/LBL) (EHA 2026) - "Methods Pts 12 years and older with R/R T-ALL/LBL meeting eligibility criteria receive standard lymphodepletion with fludarabine 30mg/m2/day and cyclophosphamide 500mg/m2/day on Days -5 to –3 followed by a single infusion of CTD402 at the RP2D on Day 0...The first pt was a 49-year-old female with a history of R/R T-ALL/LBL who had received 8 prior lines of therapy, including hyper CVAD/nelarabine, FLAG-Ida/venetoclax/asparaginase, decitabine/venetoclax/daratumumab, experimental BCL2/BCLXL inhibitor, POMP, nelarabine/etoposide/cyclophosphamide, and an experimental DNA alkylating agent...Summary/Conclusion CTD402 is a universal CD7 targeted CAR-T with a cumulative experience demonstrating an acceptable safety profile and preliminary evidence of robust anti-leukemic activity in the first two pts treated on the TENACITY-01 trial. Enrollment in the global program is ongoing and supports the development of CTD402 as an "off-the-shelf", point-of-care-ready CAR-T cell..."

CAR T-Cell Therapy • Clinical • IO biomarker • Acute Lymphocytic Leukemia • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Leukemia • Lymphoblastic Lymphoma • Lymphoma • Rare Diseases • Respiratory Diseases • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • BCL2 • BCL2L1 • CD7 • TP53

SAFETY AND EFFICACY OF HCD1A-CAR T (OC-1) THERAPY, IN PATIENTS WITH RELAPSED/REFRACTORY (R/R) T-CELL ACUTE LYMPHOBLASTIC LEUKAEMIA/LYMPHOMA (T-ALL/LL): A PRE-SPECIFIED INTERIM ANALYSIS. (EHA 2026) - "Lymphodepletion consists of fludarabine 30mg/m 2 /day and cyclophosphamide 300mg/m 2 /day on days -6 to -4...Among infused patients median age was 24 years (range 11-53), 78% were male, median prior lines were 3 (range 2-6), 67% were exposed to nelarabine and 44% had a previous alloHSCT...A high response rate has been seen with OC-1 in a heavily treated population; however, relapses were the main cause of treatment failure. The trial continues to recruit patients for DL3 and DL4 as there have been no safety concerns and responses have been observed."

CAR T-Cell Therapy • Clinical • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Metabolic Disorders • Neutropenia • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • Thrombocytopenia • CD1a

A COMPREHENSIVE EVALUATION OF NELARABINE (ARA‑G) COMBINED WITH INDUCTION CHEMOTHERAPY AGENTS ACROSS T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA CELL LINES (EHA 2026) - "Methods Six T ‑ ALL cell lines (CCRF-CEM, Jurkat, MOLT-4, HPB-ALL, MOLT-16, and Peer) were treated with ara ‑ G and induction drugs (ara-C, vincristine, daunorubicin, 6-MP, and dexamethasone) in 7×7 matrix combinations. Transcriptional correlates of sensitivity and interaction patterns highlight candidate pathways that may shape response heterogeneity across T ‑ ALL subtypes. Further mechanistic validation is ongoing and will be presented at the meeting."

Preclinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • ABCG2 • NT5C2 • TSC22D3 • TUBA1A

SYNERGISTIC DRUG COMBINATIONS TARGETING NELARABINE RESISTANCE IN T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA (EHA 2026) - "Summary/Conclusion Our data identify PI3K/AKT/mTOR inhibitors and anti-apoptotic BCL-2/BCL-xL inhibitors as promising combination partners for Nelarabine in resistant T-ALL models. These combinations enhance apoptosis and reduce cell viability, supporting further mechanistic validation to improve therapeutic strategies."

IO biomarker • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • BCL2 • BCL2L1

Synergistic Drug Combinations Targeting Nelarabine Resistance in T-cell Acute Lymphoblastic Leukemia (EHA 2026) - No abstract available

Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma

Response to venetoclax-containing regimens in patients with relapsed/refractory (R/R) T-cell acute lymphoblastic leukemia (T-ALL) and lymphoblastic lymphoma (T-LBL). (ASCO 2026) - "The most common regimens were ven + hypomethylating agent (36.9%), ven + chemotherapy (15.8%), and ven + navitoclax (15.8%)...The CR/CRi rate was 41.6% in those with prior nelarabine exposure (n=12), 0% in those with prior ven exposure (n=3), 31% in those with prior asparaginase exposure (n=13), and 50% in those with prior allo-HCT (n=8)... In this cohort of R/R T-ALL/LBL patients, responses to ven-based regimens were modest compared to recently reported prospective trials. Especially given the investigation of venetoclax-based therapies in the frontline treatment of T-ALL/LBL, additional novel therapeutic approaches will need to be explored in the R/R setting."

Clinical • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Lymphoblastic Lymphoma • Lymphoma • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma

T-cell acute lymphoblastic leukemia in adults: current treatment approaches and future perspectives. (PubMed, Expert Rev Hematol) - "The availability of effective agents like venetoclax, bortezomib and daratumumab may lead to improved frontline regimens, which will be tailored according to patient's genetics and drug response profile, and relevant role of CAR-T cell is foreseen, possibly beyond R/R setting. While several issues will require further studies, including central nervous system prophylaxis and treatment optimization in young adults and older patients, these advances will ultimately lead to improved efficacy, reduced toxicities and limited indications of allo-HCT."

Journal • Review • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • Transplantation

SOHO State of the Art Updates and Next Questions: Novel Therapies in T-ALL: From CAR-T to Novel Targets. (PubMed, Clin Lymphoma Myeloma Leuk) - "We will further discuss recent clinical trials investigating the role of nelarabine and bortezomib into front-line therapy for T-ALL, highlighting the benefit of nelarabine for pediatric and adolescent/young adult patients with T-ALL seen on the Children's Oncology Group trial AALL0434 (4-year disease-free survival 92.2% for the Capizzi methotrexate + nelarabine arm). Finally, we will address new classes of targeted small molecule inhibitors, immunotherapeutics, and chimeric antigen receptor T-cell therapies under investigation in r/r T-ALL. We focus on recent trials incorporating novel immunotherapies, including a phase 2 trial of the anti-CD38 monoclonal antibody daratumumab in combination with chemotherapy which demonstrated an overall response rate of ∼80% as well as numerous early-phase chimeric antigen receptor T-cell trials with response rates exceeding 90%."

Journal • Review • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma