methotrexate IV / Generic mfg. - LARVOL DELTA

Trials in progress - A phase I study of loncastuximab tesirine and rituximab following stereotactic radiosurgery in patients with primary and secondary central nervous system lymphomas (SOLAR) (ASH 2025) - P1 | "Exploratory endpoints include duration of response, progression-free survival, and overall survival. Correlative analysis includes minimal residual disease testing on banked diagnostic tissue and CSF from different timepoints."

Clinical • P1 data • Surgery • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • CNS Disorders • CNS Lymphoma • CNS Tumor • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Primary Central Nervous System Lymphoma • Secondary Central Nervous System Lymphoma

Real-world outcomes of HIV-associated lymphomas: A retrospective study at a single tertiary center in Saudi Arabia (ASH 2025) - "Rituximab was included in 16 cases (72%)...To our knowledge, this is the first study of its kind from the Middle East. Ongoing efforts are essential to refine treatment approaches and improve long term outcomes in this high-risk population."

Real-world • Real-world evidence • Retrospective data • Burkitt Lymphoma • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Human Immunodeficiency Virus • Infectious Disease • Lymphoma • Primary Central Nervous System Lymphoma • Septic Shock • T Cell Non-Hodgkin Lymphoma • CD4

Treatment patterns and outcomes of primary central nervous system lymphoma treated with high-dose methotrexate with or without autologous stem cell transplantation or whole brain radiation in the rea-world setting (ASH 2025) - "During induction, 59% received HDMTX+rituximab (R), 39% received HDMTX+R+additional (A) chemotherapy such as temozolomide (MTR) (15%) and cytarabine/thiotepa (MATRix) (15%)...Thiotepa (TT)/BCNU was used for conditioning in 8 patients, and TT/Busulfan/Cyclophosphamide in 1... HDMTX-based induction chemotherapy is effective in patients with PCNSL, even in those with delayed diagnosis or initiation of therapy. Although a minority of patients received consolidation with ASCT, it was associated with 100% progression-free survival."

B Cell Lymphoma • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Primary Central Nervous System Lymphoma • Pulmonary Disease • Respiratory Diseases • Transplantation

Impact of primary CNS prophylaxis in high CNS-IPI DLBCL: Analysis from the czech national lymphoma registry (ASH 2025) - P=N/A | "As conventional chemotherapeutics used in 1st line treatment do not effectively cross the blood-brain barrier, prophylactic methotrexate (MTX) or cytarabine (AraC) can be added intravenously or directly as intrathecal injection to selected patients (pts) based on risk factors...In total, 1196 pts with DLBCL diagnosed between 2010 and 2021 and treated initially with R-CHOP, either at the Charles University General Hospital in Prague or the University Hospital Brno, were included, of which 338 had low (0-1), 528 intermediate (2-3), and 330 high (>3) CNS-IPI, respectively...These data are consistent with a growing body of evidence suggesting that IV CNS prophylaxis may be an ineffective practice in 1st line DLBCL treatment, but prospective studies are needed to confirm this hypothesis. Supported by grants: NU23-03-00127 and NU21-03-00411"

B Cell Lymphoma • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma

Safety and efficacy of glofitamab in combination with lenalidomide in relapsed or refractory central nervous system lymphoma: Real-world data (ASH 2025) - "Pretreatment with obinutuzumab (1000 mg) was administered intravenously 7 days before the first dose of glofitamab. Glofitamab was then administered intravenously by step-up dosing during cycle 1 (day 8: 2.5 mg; day 15: 10 mg), followed by fixed-dose glofitamab 30 mg on day 1 of cycles 2~12 To mitigate the risk of cytokine release syndrome (CRS), patients received premedication (dexamethasone 20mg intravenously, acetaminophen 1000mg orally, isopropanazine 25mg intramuscularly) 1 hour before glofitamab therapy... The cohort comprised one male and three females, with a mean age of 58 years (range: 51~69). Median time to relapse after last treatment was 5 months (range: 3~8). Relapse symptoms included neurological symptoms (such as headache, lethargy, limb weakness, gait disturbance, slurred speech, visual deficits, etc.) and systemic symptoms (such as nausea, anorexia, fatigue, etc.) After two cycles of treatment, all patients achieved rapid remission (two complete..."

Clinical • Combination therapy • Real-world • Real-world evidence • Anorexia • B Cell Lymphoma • Brain Cancer • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Solid Tumor • CD20

Anti-CD19 chimeric antigen receptor T-cells therapy (CAR-T) is effective in secondary cns lymphoma (SCNSL) refractory to high-dose methotrexate (HDMTX)-based chemotherapy (ASH 2025) - " 23 pts were referred to holding: 6 partial-brain irradiation, 4 intrathecal CHT, 2 polatuzumab vedotin, 5 ibrutinib, 1 HD-ifosfamide-based CHT, 2 MATRix regimen, 1 thiotepa-based ASCT, combinations of these strategies in 2...Only one pt experienced G3-4 CRS, all CRS cases were successfully treated with tocilizumab and steroids, anakinra was used in 2 cases... Varied presentation and high aggressivity of SCNSL impede the use of a uniform treatment for these pts. SCNSL refractory to HDMTX-based polyCHT can benefit significantly from a tailored multimodal holding based on the pt's history and extension of disease. Only pts with good PS and responsive to holding therapy should be offered CAR-T to avoid superfluous toxicity."

CAR T-Cell Therapy • B Cell Lymphoma • CNS Disorders • CNS Lymphoma • Epilepsy • Hematological Disorders • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Secondary Central Nervous System Lymphoma

Efficacy and safety of bmetl regimen (Orelabrutinib plus Semustine, Temozolomide and Lenalidomide) with subsequent maintenance treatment in elderly/frail patients with CNSL (ASH 2025) - "After induction therapy, patients with objective response received sequential MT regimen (methotrexate 3 mg/m 2 , day 1; thiotepa 20 mg/m 2 , day 2) in a 21-day cycle for 2-4 cycles... BMeTL regimen with subsequent maintenance treatment is effective and well-tolerated for elderly/frail patients with CNSL. This study provides a potential novel strategy for this elderly/frail population."

Clinical • Agranulocytosis • CNS Lymphoma • Geriatric Disorders • Granulocytopenia • Hematological Malignancies • Infectious Disease • Lymphoma • Primary Central Nervous System Lymphoma • Secondary Central Nervous System Lymphoma • Thrombocytopenia

Efficacy and Safety of Zanubrutinib Combined with Rituximab and High-Dose Methotrexate in the Treatment of Central Nervous System Diffuse Large B-Cell Lymphoma (ASH 2025) - "The zanubrutinib combined with R + HD-MTX regimen shows good efficacy and controllable safety in patients with CNS DLBCL, which may improve the prognosis of patients and is worthy of further research."

Clinical • Atrial Fibrillation • B Cell Lymphoma • Bone Marrow Transplantation • Cardiovascular • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Infectious Disease • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Primary Central Nervous System Lymphoma • Renal Disease • Respiratory Diseases • Secondary Central Nervous System Lymphoma • Thrombocytopenia • CD79B • MYD88

Efficacy of zanubrutinib maintenance in patients with primary CNS lymphoma achieving complete response: A phase II study (ASH 2025) - "This study demonstrates clinical benefits with zanubrutinib maintenance therapy following MTX-based chemotherapy in PCNSL patients achieving CR. Long-term follow-up is needed to further validate these findings."

Clinical • P2 data • CNS Disorders • CNS Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Primary Central Nervous System Lymphoma

A real-world analysis of primary mediastinal large B-cell lymphoma: A single center study in China (ASH 2025) - "Polatuzumab vedotin, an anti-CD79b monoclonal antibody, when combined with rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP), offers the benefits of more convenient administration and comparable safety to the R- CHOP regimen, while demonstrating reduced toxicity comparison to DA-EPOCH-R...Another patient attained CMR following R-ESHAP treatment for lymph node relapse, whereas one succumbed to CNS relapse despite receiving multiple therapies, including surgery, HD-MTX BV, selinexor, and thiotepa.5 patients received targeted therapies...Summary/Conclusion POLA-R-CHP shows potential as an efficient therapy for PMBCL. Its frontline application could enhance overall response rates while reducing treatment-related toxicity."

Clinical • Real-world • Real-world evidence • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Nephrology • Non-Hodgkin’s Lymphoma • Primary Mediastinal Large B-Cell Lymphoma • Renal Disease • Respiratory Diseases • CD79B

Safety and feasibility of high dose methotrexate addition to R-CHOP chemotherapy for prophylaxis and treatment of secondary cns involvement by large B-cell lymphoma in a community-based hospital setting (ASH 2025) - "HDMTX is administered in a hospital setting with continuous intravenous fluids, urine alkalinization, drug level monitoring, and leucovorin rescue... Addition of HDMTX to R-CHOP for prophylaxis and treatment of SCNSL is feasible and safe in a community-based hospital setting. Clinical outcomes in our SCNSL cohort are similar to real-world reports from academic centers. Administering HDMTX prophylaxis concurrently with R-CHOP early in the course of treatment may minimize the risk of CNS relapse in high-risk LBCL patients."

Clinical • Acute Kidney Injury • B Cell Lymphoma • CNS Disorders • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Mucositis • Nephrology • Non-Hodgkin’s Lymphoma • Primary Central Nervous System Lymphoma • Renal Disease • Secondary Central Nervous System Lymphoma

Impact of central nervous system prophylaxis on survival outcomes in patients with primary testicular diffuse large B-cell lymphoma: A single-center analysis (ASH 2025) - "The majority of patients received first-line therapy with R-CHOP (63%), 3 patients (6.5%) received R-CHOP+BTKi, and the remainder receiving other chemotherapy regimens...In contrast, elevated LDH levels, decreased hemoglobin, abnormal lymphocyte counts, presence of B symptoms, and a high IPI score were all significantly associated with poorer outcomes. These results highlight the potential importance of CNS-directed strategies and consolidative radiotherapy in PTL and warrant validation in larger, prospective studies."

Clinical • IO biomarker • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • BCL2

Factors associated with clinically significant systemic methotrexate absorption following intrathecal methotrexate administration - a prospective Study (ASH 2025) - "Although no significant MTX-associated toxicity was noted in this cohort, these data identify patients at risk for whom prophylactic measures to mitigate potential systemic MTX toxicity after IT administration may be appropriate. This study continues to enroll."

Clinical • Bone Marrow Transplantation

Balancing risk and benefit: Fluoroquinolone prophylaxis in hyper-CVAD for acute lymphoblastic leukemia in a high fluoroquinolone-resistance setting (ASH 2025) - "The Hyper-CVADprotocol included alternating cycles of cyclophosphamide-dexamethasone-doxorubicin-vincristine (FA)and high-dose methotrexate-cytarabine (FB)... In this cohort of adults with ALL treated with Hyper-CVAD in a high-resistance, resource-limited setting, fluoroquinolone prophylaxis was associated with significantly reduced rates of febrileneutropenia and infection-related mortality. These findings support the selective use of prophylaxiswithin a structured antimicrobial stewardship framework, even in regions with rising resistance, as afeasible strategy to mitigate infectious morbidity and mortality in ALL."

Acute Lymphocytic Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • ABL1 • BCR

Increased incidence of delayed methotrexate elimination in pediatric patients with Philadelphia-chromosome positive (Ph+) or ABL-class fusion positive (ABL-Class) acute lymphoblastic leukemia treated with imatinib: Results of a retrospective cohort study by the italian association of pediatric hematology-oncology (AIEOP) (ASH 2025) - P3 | "The two protocols had very similar supportive care guidelines for the managementof HDMTX: hyperhydration (3000 ml/m²/day) with sodium bicarbonate (100 mEq/m²/day) and folinic acidadministration (7.5 mg/m²/dose IV levo-product) at fixed time points (42h, 48h, and 54h post-infusion).Based on serum MTX levels measured at the time points (T24, T42, T48h post-infusion), hyperhydrationand folinic acid rescue could be modified by protocol... This is the largest currently available study reporting the clinical and pharmacologicaleffects of imatinib given during HDMTX. Our findings suggest that the concurrent administration ofimatinib during HDMTX is associated with an increased rate of mild to severe DME but does notsignificantly increase the incidence of typical HDMTX-related toxicities. Further prospective studies areneeded to determine whether a short discontinuation of imatinib during HDMTX may contribute to asafer HDMTX administration without..."

Retrospective data • Acute Kidney Injury • Acute Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Mucositis • Nephrology • Pediatrics • Renal Disease

Patterns, risk factors and management of CD19-directed chimeric antigen receptor T-cell therapy failure in CNS lymphoma (ASH 2025) - "Notably,peripheral CD19+-B-cell aplasia suggested persistence of CD19-CAR T-cells in 93% of patients at PD.Salvage immune checkpoint inhibition (pembrolizumab, nivolumab), and lenalidomide with rituximab ortafasitamab yielded prolonged responses in a subset of patients, often exceeding 5 months... Our study identifies novel radiological risk factors for CD19-CAR failure in patients withCNSL, namely peripheral CE and LMD prior to CD19-CAR, which may guide prognostic stratification atbaseline. Outcome after CD19-CAR failure remains poor, underlining the need for rational salvagetreatments. In patients progressing after CD19-CAR therapy, we noted encouraging responses aftersalvage ICI and lenalidomide combined with rituximab/tafasitamab, which warrant further investigationin prospective studies."

CAR T-Cell Therapy • Clinical • IO biomarker • CNS Disorders • CNS Lymphoma • Hematological Malignancies • Lymphoma

A multifunctional nanoplatform for ferroptosis inducing/chemo/photothermal therapy enhances therapeutic effect and prevents adverse gastrointestinal reaction of methotrexate (ASH 2025) - "A novel multifunctional nanoplatform combining ferroptosis induction, chemotherapy, andphotothermal therapy demonstrated superior therapeutic efficacy and reduced toxicity in treatingaggressive lymphoma. This strategy presents a promising avenue for clinical translation."

Burkitt Lymphoma • Hematological Malignancies • Lymphoma • CLDN1 • DHFR • OCLN • TJP1

Efficacy and safety of rituximab, high-dose methotrexate, and thiotepa (R-MT) as first-line induction therapy for primary central nervous system diffuse large B-cell lymphoma (ASH 2025) - "The IELSG 32 study confirmed that a thiotepa-containing multi-drugcombination regimen (rituximab + high-dose methotrexate + cytarabine + thiotepa, MATrix) achieves anoverall objective response rate (ORR) of 87% when used as induction therapy for PCNSL...At a median follow-up of 19 months, the 2-year PFS rateand OS rate were 63.9% and 82.9%, respectively.Based on subsequent treatment strategies, patients were divided into three groups: 15 patients receivedinduction therapy alone, 16 patients received sequential maintenance therapy (including Bruton tyrosinekinase inhibitors [BTKi: 7 with zanubrutinib, 4 with orelabrutinib] or immunomodulatory drugs [IMiD: 5with lenalidomide, 1 with pomalidomide]), and 5 patients received ASCT as consolidation therapy.Subgroup analysis showed that the proportion of patients aged > 60 years in the sequential maintenancetherapy group was 81.3%, which was significantly higher than that in the other two groups (81.3% vs.53.3% vs. 0%,..."

Clinical • B Cell Lymphoma • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Infectious Disease • Leukopenia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Primary Central Nervous System Lymphoma • Respiratory Diseases

Chemotherapy-free induction with pomalidomide, orelabrutinib, and rituximab (POR) followed by high-dose methotrexate,rituximab and orelabrutinin (ROM) in newly diagnosed primary CNS lymphoma: Interim analysis of a phase II study (ASH 2025) - P2 | "The data cut-off date was 15th July 2025, 33 patients were enrolled in this study. The median age was 59years (range, 22-79 years). 11 patients had eye involvement and 2 patient had leptomeningesinvolvement."

P2 data • Bone Marrow Transplantation • CNS Lymphoma • Dermatology • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Leukopenia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Primary Central Nervous System Lymphoma • Thrombocytopenia

Impact of systemic high-dose MTX and BTK inhibitors on outcomes in vitreoretinal lymphoma: A multicenter retrospective analysis (ASH 2025) - "While intravitreal methotrexate (IV-MTX) remains a local cornerstone, the role ofsystemic prophylaxis—particularly high-dose MTX (HD-MTX) and Bruton's tyrosine kinase inhibitors (BTKi)—in preventing CNS relapse and improving survival requires further validation. We retrospectively analyzed 49 VRL patients, including 42 primary VRL (PVRL), 1 PCNSL withsubsequent ocular involvement, and 6 concurrent PCNSL-VRL... This study underscores the critical role of HD-MTX-based systemic therapy in improving PFSand reducing CNS progression in VRL, supporting its integration for CNS prophylaxis. Although BTKidemonstrated clinical activity, its standalone use did not significantly enhance PFS, suggesting potentialsynergy when combined with HD-MTX. Prospective studies are warranted to optimize combinatorialstrategies and validate the long-term survival benefit of CNS-directed systemic therapy in VRL."

Retrospective data • CNS Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Primary Central Nervous System Lymphoma

Orelabrutinib plus anti-PD-1 antibody and fotemustine for newly diagnosed primary central nervous system lymphoma: Phase I/II results (ASH 2025) - P1/2 | "Orelabrutinib plus anti–PD-1 antibody and fotemustine demonstrated promising activity andacceptable safety in newly diagnosed PCNSL, with a high objective response rate. These findings supportthe potential of orelabrutinib-based chemoimmunotherapy as a promising frontline strategy. The studyis still ongoing and final results will be presented in the future."

P1/2 data • B Cell Lymphoma • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Infectious Disease • Leukopenia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Primary Central Nervous System Lymphoma • Respiratory Diseases • Thrombocytopenia

Zanubrutinib combined with intrathecal chemotherapy for prevention of CNS relapse in high-risk diffuse large B-cell lymphoma (ASH 2025) - P4 | "Patients received six cycles of standard immunochemotherapy (R-CHOP or Pola-R-CHP) every 21-day per cycle, combined with zanubrutinib (160mg twice daily) and ITchemotherapy (methotrexate 12mg plus dexamethasone 5mg on day 2 of each cycle, ≥4 doses)... Zanubrutinib combined with R-CHOP or Pola-R-CHP and IT chemotherapy demonstrated high responserate and low CNS relapse rate in high-risk DLBCL with favorable safety profiles. High CSF penetration ofzanubrutinib support its potential role in CNS prophylaxis."

B Cell Lymphoma • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Pneumonia • Respiratory Diseases • Secondary Central Nervous System Lymphoma • Thrombocytopenia

NB02 (Poseltinib) combined rituximab and lenalidomide in R/ R PCNSL (POTENTIAL-P): Initial results of safety lead-in cohort. (ASH 2025) - P2 | "These initial results from the safety lead-in cohort suggest that the combination of poseltinib, rituximab,and lenalidomide has a manageable safety profile and demonstrates promising preliminary anti-tumoractivity in patients with R/R PCNSL. Enrollment in the study is ongoing, and updated results will bepresented."

Clinical • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • CNS Lymphoma • Hematological Disorders • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Primary Central Nervous System Lymphoma • Thrombocytopenia

Treatment intensity and region of diagnosis affect survival in primary CNS lymphoma in England: A national cohort study from the uncover project. (ASH 2025) - "Intensive HD-MTX regimens were defined as including high dose cytarabine with or without thiotepa. HD-MTX alone orwith less intensive agents such as procarbazine were considered non-intensive...Patients receiving urgent chemotherapy had worse OS. Patients who undergoASCT experience have very good outcomes, although its application as first-line consolidation for PCNSLvaries markedly between regions, potentially contributing to geographical variation in survival."

CNS Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Primary Central Nervous System Lymphoma

Comparative analysis of consolidation strategies after induction chemotherapy in primary central nervous system lymphoma (ASH 2025) - "A total of 394 patients received HD-MTX-based induction: HD-MTX alone(n=130), methotrexate/procarbazine/vincristine (MPV, n=68), or rituximab-MPV (R-MPV, n=123)...Patients were categorized into five consolidation strategies:HDC-ASCT (n=160), whole brain radiotherapy (WBRT, n=14), high-dose cytarabine (Ara-C, n=83),etoposide/Ara-C (EA, n=34), and observation without consolidation (n=26)... In this large, single-center cohort with long-term follow-up, HDC-ASCT was the onlyconsolidation strategy that provided a significant survival benefit in patients with PCNSL. These findingssuggest limited benefit from reduced-intensity chemotherapy or WBRT as consolidation therapy. Ourresults highlight the need for alternative effective strategies for PCNSL patients who are not eligible forHDC-ASCT."

B Cell Lymphoma • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Primary Central Nervous System Lymphoma