methotrexate IV / Generic mfg. - LARVOL DELTA

CLAMP: A phase II prospective study of camrelizumab combined with pegaspargase, etoposide, and high-dose methotrexate in patients with natural killer (NK)/T-cell lymphoma. (ASCO 2024) - "The CLAMP regimen is effective and safe and seems to reduce the incidence of CNS involvement and HLH. The CLAMP regimen may be a promising option in the treatment of NKTCL lymphoma."

Clinical • P2 data • Hematological Malignancies • Immunology • Infectious Disease • Lymphoma • Oncology • Rare Diseases • T Cell Non-Hodgkin Lymphoma

High-Dose Methotrexate Containing Induction Chemotherapy Followed By Nivolumab Consolidation in Older (≥ 65) Patients with Previously Untreated Primary CNS Lymphoma (ASH 2023) - P1 | "Variations of the following regimens were used for induction: 43% R-MPV (rituximab, methotrexate, procarbazine, and vincristine) (43%), 29% MRT (methotrexate, rituximab, and temozolomide), 21% MR (methotrexate and rituximab), and 7% MATRix (methotrexate, cytarabine, thiotepa, and rituximab)... The current study demonstrates encouraging safety and clinical outcomes of nivolumab consolidation in older PCNSL patients who are deemed poor candidates for ASCT or WBI. No DLT was observed during the safety run-in phase, and there was no unexpected toxicity associated with nivolumab although 1 patient discontinued the study treatment due to Stevens-Johnson syndrome, a rare but known AE associated with nivolumab, after Cycle 1. Overall, nivolumab consolidation was associated with favorable survival rates in a group of patients with poor-risk PCNSL."

Clinical • Acute Kidney Injury • CNS Lymphoma • Fatigue • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Nephrology • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma • Renal Disease • Septic Shock • Steven-Johnson Syndrome

Comparison of Thiotepa, Busulfan, and Cyclophosphamide Versus Busulfan and Thiotepa Conditioning Regimens in Autologous Stem Cell Transplantation for Primary CNS Lymphoma: A Multicenter Retrospective Analysis. (PubMed, Hematol Oncol) - "We retrospectively analyzed patients aged ≤ 60 years who underwent ASCT with thiotepa-busulfan-cyclophosphamide (TBC) or busulfan-thiotepa (BuTT) conditioning after high-dose methotrexate-based induction at two Korean institutions between 2015 and 2023...In younger patients with PCNSL, TBC demonstrated a trend toward more durable disease control than BuTT, with manageable toxicity. As the thiotepa dose represents the major distinction between regimens, dose-intensified thiotepa strategies with adjusted partner agents merit further prospective investigation."

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

A PHASE II TRIAL OF TAGRAXOFUSP, HYPER-CVAD, AND VENETOCLAX FOR PATIENTS WITH NEWLY DIAGNOSED OR RELAPSED/REFRACTORY BPDCN (EHA 2026) - P2 | "Methods Adults ( > 18 years [yrs]) w/ ND or R/R BPDCN received: Cycle [C] 1: TAG days [d] 1-5; C2, 4, 6, 8: TAG d1 – 5 w/ VEN d2 – 14 (C2) and d1 – 7 (C4, 6, 8); C3, 7: VEN d1 – 7 w/ Hyper-CVAD or mini-hyper-CVD; C5: VEN d1 – 7 w/ high-dose methotrexate/cytarabine or mini-methotrexate/cytarabine...This abstract was accepted and previously presented at the 2026 ASCO Annual Meeting. Overall Survival in Frontline (A) and Relapsed/Refractory (B)."

Clinical • P2 data • Hematological Malignancies • Infectious Disease • Myelodysplastic Syndrome • Respiratory Diseases • Septic Shock • ASXL1 • CD123 • DNMT3A • IL3RA • KRAS • NRAS • TET2

Ibrutinib in combination with rituximab, methotrexate, vincristine, and procarbazine (R-MVP/i) for newly diagnosed primary CNS lymphoma (PCNSL). (PubMed, Neuro Oncol) - "R-MVP/i was well tolerated and associated with excellent disease control and survival."

Journal • CNS Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma • Thrombocytopenia • Transplantation

High-Dose Methotrexate, Ibrutinib and Temozolomide (MIT) for the Treatment of Newly Diagnosed Primary Central Nervous System Lymphoma: A Multi-Center Prospective Phase II Study (ASH 2023) - P2 | "The novel induction treatment of MIT achieved encouraging responses in newly diagnosed PCNSL patients with acceptable toxicities. The early clearance of ctDNA in CSF may be related to favorable survival."

Clinical • P2 data • Atrial Fibrillation • B Cell Lymphoma • Cardiovascular • CNS Disorders • CNS Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma • Thrombocytopenia • BTG2 • CD79B • MYD88 • PIM1

Radiotherapy or Autologous Stem-Cell Transplantation for Primary CNS Lymphoma in Patients Age 60 Years and Younger: Long-Term Results of the Randomized Phase II PRECIS Study. (PubMed, J Clin Oncol) - "Patients were treated with high-dose methotrexate-based induction chemotherapy followed by whole-brain radiotherapy (WBRT) or high-dose chemotherapy (thiotepa-busulfan-cyclophosphamide) with autologous stem-cell transplantation (ASCT)...Balance (52% v 10%, P ≤ 0.001) and neurocognition (64% v 13%, P < .001) significantly deteriorated after WBRT compared with ASCT during the follow-up. This study shows that 40 Gy WBRT should be avoided in first-line treatment because of its neurotoxicity and suboptimal efficacy in reducing relapses while ASCT appears to be highly efficient in preventing relapses."

Journal • P2 data • Bone Marrow Transplantation • CNS Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation

NCI-2018-01752: Naive T Cell Depletion for Preventing Chronic Graft-versus-Host Disease in Children and Young Adults With Blood Cancers Undergoing Donor Stem Cell Transplant (clinicaltrials.gov) - P2 | N=45 | Active, not recruiting | Sponsor: Fred Hutchinson Cancer Center | Recruiting ➔ Active, not recruiting | N=68 ➔ 45

Enrollment change • Enrollment closed • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Burkitt Lymphoma • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Lymphoma • Mast Cell Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Non-Hodgkin’s Lymphoma • Oncology • Transplantation • HLA-B • HLA-C • HLA-DRB1

Effects on Survival of Non-Myeloablative Chemoimmunotherapy Compared to High-Dose Chemotherapy Followed By Autologous Stem Cell Transplantation (HDC-ASCT) As Consolidation Therapy in Patients with Primary CNS Lymphoma - Results of an International Randomized Phase III Trial (MATRix/IELSG43) (ASH 2022) - P3 | "Induction consisted of 4 cycles of MATRix regimen (rituximab 375 mg/m2/d days 0 & 5; methotrexate 3.5 g/m2 day 1; cytarabine 2 × 2 g/m2/d days 2 & 3; thiotepa 30 mg/m2 day 4, every 21 days)...Pts achieving at least partial response (PR) after completion of induction were randomly allocated to either arm A with two courses of R-DeVIC regimen (375 mg/m2 day 0; dexamethasone 40 mg/d days 1 to 3; etoposide 100 mg/m2/d days 1 to 3; ifosfamide 1500 mg/m2/d days 1 to 3; carboplatin 300 mg/m2 day 1); or arm B, consisting of HDC with BCNU 400 mg/m2 (day -6) and thiotepa 2 x 5 mg/kg/d days -5 & -4) followed by ASCT... This international randomized phase III trial demonstrates that consolidation with HDC-ASCT results in significantly better outcome than non-myeloablative chemoimmunotherapy. This comes along without any measurable negative effect on neurocognitive functions and with an excellent risk-to-benefit ratio. HDC-ASCT is the standard consolidation..."

Clinical • Late-breaking abstract • P3 data • Bone Marrow Transplantation • CNS Lymphoma • Hematological Malignancies • Human Immunodeficiency Virus • Infectious Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation

A phase II trial of tagraxofusp, hyper-CVAD, and venetoclax for patients with newly diagnosed or relapsed/refractory BPDCN. (ASCO 2026) - P2 | " Adults (≥18 years [yrs]) w/ ND or R/R BPDCN received: Cycle [C] 1: TAG days [d] 1-5; C2, 4, 6, 8: TAG d1 – 5 w/ VEN d2 – 14 (C2) and d1 – 7 (C4, 6, 8); C3, 7: VEN d1 – 7 w/ Hyper-CVAD or mini-hyper-CVD; C5: VEN d1 – 7 w/ high-dose methotrexate/cytarabine or mini-methotrexate/cytarabine... As frontline therapy, TAG with Hyper-CVAD, and VEN shows promising safety with no early mortality or high-grade CLS, with high response rates enabling frequent SCT consolidation and no CNS relapse."

Clinical • P2 data • Hematological Malignancies • Infectious Disease • Oncology • Respiratory Diseases • Septic Shock • ASXL1 • CD123 • DNMT3A • IL3RA • KRAS • NRAS • TET2

Phase 1 Study of Escalating Doses of Ibrutinib in Teddi-R with Isavuconazole for Relapsed and Refractory Primary DLBCL of the CNS (ASH 2024) - P1 | "We have previously shown that ibrutinib with temozolomide, etoposide, liposomal doxorubicin, dexamethasone, and rituximab (TEDDI-R) induces durable remissions in relapsed/refractory PCNSL without the need for consolidation, but risks Aspergillus (Lionakis et al...Pts received up to 6 cycles of TEDDI-R with intra-Ommaya cytarabine and no planned maintenance or consolidation...TEDDI-R induces a high rate of complete response in patients with relapsed/refractory PCNSL including those refractory to HD-MTX. Remissions can be durable without consolidation."

P1 data • Atrial Fibrillation • Cardiovascular • CNS Lymphoma • Dermatology • Diffuse Large B Cell Lymphoma • Febrile Neutropenia • Hepatitis B • Hepatology • Human Immunodeficiency Virus • Hypertension • Infectious Disease • Mucositis • Neutropenia • Primary Central Nervous System Lymphoma • Thrombocytopenia • Venous Thromboembolism • Ventricular Tachycardia

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

MRG003-010: A Study to Evaluate MRG003 vs Cetuximab/Methotrexate in in the Treatment of Patients With RM-SCCHN (clinicaltrials.gov) - P3 | N=180 | Recruiting | Sponsor: Lepu Biopharma Co., Ltd. | Not yet recruiting ➔ Recruiting | Trial completion date: Dec 2025 ➔ Dec 2027 | Trial primary completion date: Aug 2025 ➔ Dec 2027

Enrollment open • Trial completion date • Trial primary completion date • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

High-dose chemotherapy followed by autologous stem-cell transplantation versus non-myeloablative consolidation in primary CNS lymphoma (MATRix/IELSG43): a randomised phase 3 trial. (PubMed, Lancet) - P3 | "In the largest randomised trial in untreated PCNSL to date, HCT-ASCT significantly improved progression-free and overall survival compared with non-myeloablative consolidation in patients who had completed induction treatment, establishing it as the preferred consolidation strategy in fit patients."

Journal • P3 data • Acute Myelogenous Leukemia • Cardiovascular • CNS Lymphoma • Hematological Malignancies • Human Immunodeficiency Virus • Infectious Disease • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma • Pulmonary Embolism • Respiratory Diseases • Transplantation

Phase 2 Response-Adapted Study of Ibrutinib with Temozolomide, Etoposide, Liposomal Doxorubicin, Dexamethasone, and Rituximab (TEDDI-R) for Secondary CNS Lymphoma (ASH 2023) - P2 | "Pts receive isavuconazole as fungal prophylaxis throughout therapy... Pts with ibrutinib-responsive SCNSL achieve a high rate of CR to TEDDI-R, and preliminary data suggest these remissions are durable. Most ibrutinib-responsive tumors are CD10-negative and enriched for MCD and BN2. TEDDI-R can be delivered as an outpatient to pts of all ages."

P2 data • Anemia • Anorexia • Atrial Fibrillation • B Cell Lymphoma • Cardiovascular • CNS Lymphoma • CNS Tumor • Dermatology • Diffuse Large B Cell Lymphoma • Endocrine Disorders • Fatigue • Febrile Neutropenia • Hematological Malignancies • Human Immunodeficiency Virus • Hypotension • Infectious Disease • Lymphoma • Nephrology • Neutropenia • Non-Hodgkin’s Lymphoma • Pneumonia • Primary Central Nervous System Lymphoma • Renal Disease • Respiratory Diseases • Secondary Central Nervous System Lymphoma • Septic Shock • Thrombocytopenia • BCL2 • BCL6 • MME • MYC

A051901: Testing the Addition of Lenalidomide and Nivolumab to the Usual Treatment for Primary CNS Lymphoma (clinicaltrials.gov) - P1 | N=47 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Recruiting ➔ Active, not recruiting

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

A Pilot Study of Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Lenalidomide (VIPOR) for Diffuse Large B-Cell Lymphoma Involving the Central Nervous System (ASH 2024) - "The study was amended to treat with VIPOR only without nivolumab and no window...VIPOR can overcome treatment resistance to both HD-MTX and BTKi-based therapy, although durable remissions may be more likely in BTKi-naïve patients. Further studies testing multi-targeted combination regimens are warranted in both PCNSL and SCNSL."

Clinical • Anemia • Autoimmune Hepatitis • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Cardiovascular • CNS Disorders • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Febrile Neutropenia • Hepatology • Immunology • Infectious Disease • Lymphoma • Myocardial Infarction • Nephrology • Neutropenia • Non-Hodgkin’s Lymphoma • Pneumonia • Primary Central Nervous System Lymphoma • Renal Disease • Respiratory Diseases • Secondary Central Nervous System Lymphoma • Thrombocytopenia

Results of the primary end-point of the LOC-R01: A randomized phase II Study of lenalidomide and ibrutinib in association with rituximab-methotrexate procarbazine vincristin (R-MPV) as a targeted induction treatment for patients aged 18 to 65 with a newly diagnosed primary central nervous system lymphoma (PCNSL) (ASH 2025) - P1/2 | "Background : With standard high-dose methotrexate (HDMTX) and cytarabine (HDAraC)-basedinductions, half of the patients achieved complete response (CR)...Responders received two cycles of HDAraCfollowed by HD thiotepa-busulfan and ASCT... Both arms met the predetermined threshold of efficacy with 86% and 82% of CR/CRurates in the lenalidomide and ibrutinib arm, respectively. R-MPV plus a BTK-inhibitor or animmunomodulatory drug constitutes an interesting first-line induction for PCNSL patients up to 65 years.Correlation of patient, disease and lymphoid subpopulations characteristics with response in eachtreatment arm will be explored to guide the choice of the targeted therapy. Ancillary studies regardingthe prognostic impact of baseline and end of induction levels of cytokines in the CSF, ctDNA inplasma/CSF and radiomic features, as biomarkers of response, are planned."

Clinical • IO biomarker • P2 data • CNS Disorders • CNS Lymphoma • Hematological Malignancies • Hepatology • Lymphoma • Mental Retardation • Non-Hodgkin’s Lymphoma • Primary Central Nervous System Lymphoma • Steven-Johnson Syndrome • CD4 • ICOS • PD-1

A phase I/II study of thiotepa-based immunochemotherapy in relapsed/refractory primary CNS lymphoma: the TIER trial. (PubMed, Blood Adv) - "This multicenter, phase I/II study investigated thiotepa in combination with ifosfamide, etoposide and rituximab (TIER), for the treatment of PCNSL relapsed or refractory to high-dose methotrexate-based chemotherapy...The TIER regimen can be safely delivered and is active against rrPCNSL, and followed by ASCT can provide durable remission and long-term survival. However, for the majority of patients, prognosis remains poor and novel treatment strategies are urgently needed."

Journal • P1/2 data • Bone Marrow Transplantation • CNS Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Thrombocytopenia • Transplantation

Penpulimab combined with rituximab, high-dose methotrexate, and cytarabine (Pen-RMA) in newly diagnosed primary central nervous system lymphoma (PCNSL): a phase 2 trial. (PubMed, Blood Cancer J) - P2 | "Among them, 8 had CSF ctDNA clearance while 6 were positive. Overall, Pen-RMA regimen demonstrated encouraging antitumor activity with a manageable toxicity in PCNSL."

Journal • P2 data • CNS Lymphoma • Hematological Disorders • Hematological Malignancies • Leukopenia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma • Thrombocytopenia • Transplantation

Biomarker-Driven Treatment Strategy in High-Risk Large B-Cell Lymphoma: Final Results of a Nordic Phase 2 Study (ASH 2022) - "All patients received two cycles of R-CHOP-21 with high dose methotrexate (HD) on day 15 and depending on the biological risk factors either four additional courses of biweekly R-CHOP with etoposide (R-CHOEP-14; no biological risk factors) or four courses of dose-adjusted etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, and rituximab (DA-EPOCH-R; biological risk factors). In addition, one course of R-HD-cytarabine was given to all patients... Stratification according to biological risk factors is feasible. Safety and efficacy results are encouraging and comparable to our previous study with low number of treatment failures and favorable survival rates. Furthermore, our results indicate that treatment intensification can overcome the adverse impact of biological risk factors, apart from 17p/TP53 deletion."

Biomarker • Clinical • IO biomarker • P2 data • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • CD5 • MYC • TP53

BIOMARKER-ADAPTED TREATMENT IN HIGH-RISK LARGE B-CELL LYMPHOMA: LONG-TERM FOLLOW-UP OF A NORDIC PHASE II TRIAL (EHA 2024) - "Treatment consisted of twocycles R-CHOP and high-dose methotrexate (HD-Mtx) and depending on the biological risk factors either fouradditional courses of biweekly R-CHOP with etoposide (R-CHOEP-14; no biological risk factors) or four coursesof DA-EPOCH-R (biological risk factors). In addition, one course of R and HD-cytarabine was given to allpatients... Intensified immunochemotherapy results in a favorable outcome in patients with high-risk LBCL. Patients with aaIPI3 and biological risk factors may benefit from the DA-EPOCH-R-based regimen. Intensified treatment can overcome the adverse impact of biological risk factors apart from TP53 aberrations,high ctDNA burden, and/or MRD positivity."

Biomarker • IO biomarker • P2 data • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • CD5 • MYC • TP53

Blinatumomab and Ponatinib for Adults with Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: Updated Results and Predictors of Relapse (ASH 2024) - "The study has now been amended to increase the number of doses of IT chemotherapy from 12 to 15 and also institutes 2 cycles of high-dose methotrexate and cytarabine for patients with high WBC. The association of genomic alterations (including IKZF1plus genotype) with MRD responses and relapse risk is being analyzed and will be presented at the meeting."

Clinical • Acute Lymphocytic Leukemia • Central Nervous System Leukemia • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • ABL1 • IKZF1

Scleredema Diabeticorum with joint involvement with response to high dose methotrexate in a 40 year old Filipino patient: A Case Report (EADV 2026) - No abstract available

Case report • Clinical • Immunology

Neurotoxicity and cognitive outcomes in modern therapies for primary central nervous system lymphoma. (PubMed, Curr Opin Oncol) - "Future therapeutic progress in PCNSL should prioritize prediction, early detection, and prevention of neurotoxicity alongside disease control."

Journal • CNS Lymphoma • Cognitive Disorders • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma • Transplantation