Muphoran (fotemustine) / Servier - LARVOL DELTA

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

Strikingly Reduced Toxicities of Fotemustine-Based Chemotherapeutics Than High-Dose Methotrexate-Containing Regimens with Comparable Efficacy (ASH 2024) - "Therefore, this study increased the sample size, extended the follow-up time and set up a control group to analyze the efficacy and safety of fotemustine-containing regimens compared with HD-MTX-containing regimens in the treatment of newly diagnosed PCNSL patients.Methods : From April 2011 to December 2021, 114 patients with newly diagnosed PCNSL who received HD-MTX-containing regimens (HD-MTX plus cytarabine [HD-MA], rituximab, HD-MTX plus temozolomide [R-MT]) or fotemustine-containing regimens (fotemustine, teniposide plus dexamethasone [FTD], fotemustine, temozolomide plus dexamethasone [FVD], rituximab, fotemustine, pemetrexed plus dexamethasone [RFPD]) were retrospectively analyzed in this study...Neither the progression free survival (PFS) (P=0.783) nor the overall survival (OS) (P=0.918) exhibited remarkably difference between HD-MTX-containing group and fotemustine-containing group. Notably, we noted that patients treated with HD-MTX-containing regimens..."

Clinical • Anemia • Brain Cancer • CNS Lymphoma • Hematological Disorders • Hematological Malignancies • Leukopenia • Lymphoma • Melanoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma • Solid Tumor • Thrombocytopenia

SUCCESSFUL FIRST-LINE TREATMENT OF ADVANCED-STAGE HEPATIC HISTIOCYTIC SARCOMA WITH TANDEM AUTOLOGOUS AND ALLOGENEIC STEM CELL TRANSPLANTATION: A CASE REPORT (SIE 2025) - "Given the patient's fitness and the aggressive course of the disease, chemotherapy was escalated to ICE regimen (etoposide, carboplatin, ifosfamide) for four cycles. Following complete metabolic response on PET, the patient underwent ASCT after FEAM (fotemustine, etoposide, cytarabine, melphalan) conditioning, without any complication...The conditioning regimen consisted of thiotepa and melphalan. GVHD prophylaxis included post-transplant cyclophosphamide, tacrolimus, and mycophenolate mofetil...Systemic HS remains a clinical challenge due to its poor prognosis. This case report may support the hypothesis that upfront high-dose chemotherapy combined with allogeneic cellular therapy could play a potential role in achieving durable complete remission."

Case report • Clinical • Metastases • Cholestasis • Graft versus Host Disease • Hematological Malignancies • Hepatology • Immunology • Lymphoma • Sarcoma • Solid Tumor • Transplantation • BRAF • CD163 • CD4 • CD68 • KRAS • MAP2K1 • NRAS

STRIKINGLY REDUCED TOXICITIES OF FOTEMUSTINE-BASED CHEMOTHERAPEUTICS THAN HIGH-DOSE METHOTREXATE-CONTAINING REGIMENS WITH COMPARABLE EFFICACY (ICML 2025) - " From April 2011 to December 2021, 114 patients with newly diagnosed PCNSL who received HD-MTX-containing regimens (HD-MTX plus cytarabine [HD-MA], rituximab, HD-MTX plus temozolomide [R-MT]) or fotemustine-containing regimens (fotemustine, teniposide plus dexamethasone [FTD], fotemustine, temozolomide plus dexamethasone [FVD], rituximab, fotemustine, pemetrexed plus dexamethasone [RFPD]) were retrospectively analyzed in this study. Fotemustine-based chemotherapeutics conferred a safer effect on newly-diagnosed PCNSL patients compared with HD-MTX-containing regimens together with comparable efficiency."

Clinical • CNS Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Primary Central Nervous System Lymphoma

A PHASE I/II STUDY OF ORELABRUTINIB COMBINED WITH ANTI-PD-1 ANTIBODY AND FOTEMUSTINE FOR PATIENTS WITH NEWLY DIAGNOSED PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA (ICML 2025) - P1/2 | "The combination of orelabrutinib, anti-PD-1 antibody, and fotemustine showed therapeutic potential in newly diagnosed PCNSL pts. However, clinically significant adverse events, particularly grade 3/4 thrombocytopenia and pulmonary infections, necessitate vigilant monitoring and proactive management to optimize patient outcomes."

Clinical • P1/2 data • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma

A PHASE I/II STUDY OF ORELABRUTINIB COMBINED WITH ANTI-PROGRAMMED CELL DEATH PROTEIN-1 ANTIBODY AND FOTEMUSTINE FOR PATIENTS WITH NEWLY DIAGNOSED PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA (PCNSL) (EHA 2025) - P1/2 | "The combination of orelabrutinib, anti-PD-1 antibody, and fotemustine showed therapeutic potential in newly diagnosed PCNSL pts. However, clinically significant AEs, particularly grade 3/4 thrombocytopenia and pulmonary infections, necessitate vigilant monitoring and proactive management to optimize patient outcomes."

Clinical • P1/2 data • Anemia • CNS Lymphoma • Dermatology • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Leukopenia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma • Psoriasis • Respiratory Diseases • Thrombocytopenia

Quantifying Nitrosoureas: Comprehensive Insights into Analytical Techniques Transforming Cancer Research. (PubMed, Crit Rev Anal Chem) - "This review provides a comprehensive overview of the analytical methodologies employed over the past forty years for the detection and quantification of five widely used nitrosourea-based anticancer drugs-carmustine (BCNU), lomustine (CCNU), semustine (methyl-CCNU), nimustine (NMT), and fotemustine (FM)-along with their metabolites. Furthermore, advancements in hybrid analytical techniques and their potential in enhancing the selectivity and sensitivity of NU detection are explored. This review aims to provide insights into the evolution of analytical approaches for nitrosourea-based drugs, highlighting their applications in pharmacokinetics, therapeutic drug monitoring, and environmental surveillance."

Journal • Review • Brain Cancer • Hematological Malignancies • Immunology • Lymphoma • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor

BEAM VS. EAM, FEAM, BEEAM, AND TEAM: EXPLORING CONDITIONING STRATEGIES IN AUTOLOGOUS STEM CELL TRANSPLANTATION FOR HODGKIN LYMPHOMA A RETROSPECTIVE STUDY OF LWP (EBMT 2025) - "BEAM (carmustine, etoposide, cytarabine, and melphalan) remains the most widely used conditioning regimen for lymphomas in Europe. However, alternatives have been developed over time to address challenges such as limited availability, high costs, or potential toxicities, notably including BeAM (substituting carmustine with bendamustine), FEAM (using fotemustine instead of carmustine), and TEAM (incorporating thiotepa)... We observed poorer outcomes for patients receiving BeAM, and better in those treated with FEAM compared to BEAM, while other conditioning regimens yielded comparable results."

Retrospective data • Bone Marrow Transplantation • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology • Transplantation

AUTOLOGOUS HSCT ACTIVITIES IN THE ERA OF IEC THERAPY: REPORT FROM A SINGLE CENTER (EBMT 2025) - "Background: Autologous HSCT in the era of Rituximab still represents a therapeutic option for patients with high risk DLBCL...The main conditioning regimen was the association of busulfan and melphalan until 2012 then we shifted to the use of the association of cytarabine, fotemustine, etoposide and melphalan... The introduction of IEC therapy represents a revolution as therapeutic alternative for high risk lymphoma, with probable and possible changes in the therapeutic algorithm. Despite that the use of high dose chemotherapy treatment with autologous HSCT consolidation, remain a standard of care stable over the years."

Clinical • Bone Marrow Transplantation • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Oncology • Septic Shock

Fotemustine in Treating Patients With Metastatic Melanoma (clinicaltrials.gov) - P2 | N=12 | Terminated | Sponsor: Institut du Cancer de Montpellier - Val d'Aurelle | N=60 ➔ 12 | Completed ➔ Terminated; In view of the slowness of the inclusions and the difficulty of carrying out the study, it was decided to put an end to this study.

Enrollment change • Trial termination • Melanoma • Oncology • Solid Tumor • MGMT

A novel machine learning model integrating clinical and molecular data to predict response to second line treatment in recurrent IDHwtglioblastoma (AIOM 2024) - "Background : Nitrosoureas (lomustine/fotemustine) and antiangiogenic drugs (bevacizumab or regorafenib) are second-line treatment options for patients with recurrent IDHwt-glioblastoma (rGBM). The multi-classification ML model developed in this study was able to identify clinical and molecular signatures of recurrent glioblastoma patients responding to specific second-line treatment with bevacizumab or regorafenib or nitrosoureas."

Clinical • Machine learning • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • CDKN2A • CDKN2B • EGFR • MTAP • PTEN • TP53

PTEN alteration as a predictor of second-line efficacy in patients with recurrent IDHwt-glioblastoma (rGBM) (AIOM 2024) - "Nitrosoureas (NS) such as lomustine and fotemustine and antiangiogenic drugs such as regorafenib(Reg) and bevacizumab (Bev) are all treatment options for rGBM. We concluded that pathogenic PTEN alteration may be a predictor of poor efficacy of regorafenib and lomustine in rGBM patients. However, a prospective study with a larger population is needed to better define the role of pTEN in these patient populations."

Clinical • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • MGMT • PTEN

Fotemustine in recurrent high‑grade glioma: MRI neuro‑radiological findings. (PubMed, Oncol Lett) - "In conclusion, the present study described a series of patients with recurrent HGG treated with FTM in monotherapy, demonstrating a prevalent increase in lesion enhancement and three cases of marked restrictions on diffusion-weighted imaging. Further prospective studies are required to corroborate such preliminary results."

Journal • Astrocytoma • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

HOW I TREAT SARS-COV-2 INFECTION DURING HEMATOPOIETIC STEM CELL TRANSPLANT BONE MARROW APLASIA: MONOCENTRIC EXPERIENCE (SIE 2024) - "It was conditioned according to FEAM protocol (fotemustine, cytarabine, etoposide and mephalan) and was undergoing to infusion of CD34-positive cell dose 7.38 x106/kg, on day 0...The patient received antiviral therapy: remdesivir 200 mg on day -2 and 100 mg on day -1 and day 0. The patient has febrile neutropenia on day +7 and he received empirical antibiotic therapy with piperacillin tazobactam, the infectious agent could not be determined, and the fever disappeared within 24 hours...Conclusion. cases of SARS-CoV-2 infection in aplasia after high-dose regimen for autologous stem cell transplantation are rare in the medical literature; in our experience, the low viral load, the absence of comorbidities, but also the promptly CT scan and the start of antiviral therapy have allowed us to have no complications from SARS-CoV-2."

Aplastic Anemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Hodgkin Lymphoma • Infectious Disease • Interstitial Lung Disease • Lymphoma • Neutropenia • Novel Coronavirus Disease • Oncology • Pneumonia • Respiratory Diseases • Transplantation

PTEN alteration as a predictor of second-line efficacy in patients with recurrent IDHwt-glioblastoma (EANO 2024) - "Nitrosoureas (NS) such as lomustine and fotemustine and antiangiogenic drugs such as regorafenib(Reg) and bevacizumab (Bev) are all treatment options for rGBM. We concluded that pathogenic PTEN alteration may be a predictor of poor efficacy of regorafenib and lomustine in rGBM patients. However, a prospective study with a larger population is needed to better define the role of PTEN."

Clinical • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • MGMT • PTEN

A novel machine learning (ML) model integrating clinical and molecular data to predict response to second line treatment in recurrent IDHwt-glioblastoma (rGBM) (EANO 2024) - "Background: Nitrosoureas (lomustine/fotemustine) and antiangiogenic drugs (bevacizumab or regorafenib) are second-line treatment options for patients with rGBM, but to date predictors of efficacy are lacking. The multi-classification ML model developed in this study was able to identify clinical and molecular signatures of rGBM responding to second-line with bevacizumab or regorafenib or nitrosoureas .This model could be useful to choose the more effective second-line therapy in rGBM patients."

Clinical • Machine learning • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • CDKN2A • CDKN2B • EGFR • MTAP • PTEN • TP53

A novel machine learning (ML) model integrating clinical and molecular data to predict response to second-line treatment in recurrent IDHwt-glioblastoma (rGBM) (ESMO 2024) - "Background: Nitrosoureas (lomustine or fotemustine) and antiangiogenic (bevacizumab or regorafenib) are second-line treatment options for patients with rGBM, but to date predictors or efficacy are lacking. The multi-classification ML model developed in this study was able to identify clinical and molecular signatures of rGBM responding to Bevacizumab,Regorafenib or Nitrosuree. This model could be useful to choose the more effective second-line therapy in rGBM."

Clinical • Machine learning • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • CDKN2A • CDKN2B • EGFR • MTAP • PTEN • TP53

PTEN alteration as a predictor of second-line efficacy in patients with recurrent IDHwt-glioblastoma (ESMO 2024) - "Background: Nitrosoureas (lomustine or fotemustine) and antiangiogenic (bevacizumab or regorafenib) are second-line treatment options for patients with rGBM, but to date predictors or efficacy are lacking. We concluded that pathogenic PTEN alteration may be a predictor of poor efficacy of regorafenib and lomustine in rGBM patients. However, a prospective study with a larger population is needed to better define the role of PTEN."

Clinical • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • MGMT • PTEN

UPFRONT AUTOLOGOUS STEM CELL TRANSPLANTATION CAN CURE A HIGH PERCENTAGE OF HIGH-INTERMEDIATE/HIGH-RISK AGGRESSIVE LYMPHOMA: RESULTS OF A MONOCENTRIC RETROSPECTIVE SERIES (EHA 2024) - "Induction treatment was R-CHOPx4 (rituximab, cyclophosphamide, doxorubicin, vincristine andprednisone) followed by R-MADx2 (rituximab, methotrexate, cytarabine and dexamethasone) in pts youngerthan 60 years (yrs), R-CHOPx6 in older pts and R-DA-EPOCH (rituximab, dose-adjusted etoposide, prednisone,vincristine, cyclophosphamide and doxorubicin) in double expressor (DE) lymphoma since 2018...All pts wereconditioned with BEAM (carmustine, etoposide, cytarabine and melphalan) or FEAM (fotemustine, etoposide,cytarabine and melphalan)...9% respectively: 3 pts died from pneumonia (2 COVID-19 after 4 and 10 months from ASCT, 1 after 114months); 9 pts had disease progression and 4 are still alive after salvage treatment (CAR-T in 2, platinum-basedtherapy and lenalidomide in 2)... Upfront ASCT consolidation is still an effective and safe strategy which can cure more than 80% of high-riskaggressive lymphoma patients with a single line of treatment. Pre-transplant PET could help as..."

IO biomarker • Retrospective data • Bone Marrow Transplantation • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Infectious Disease • Lymphoma • Mediastinal B Cell Lymphoma • Non-Hodgkin’s Lymphoma • Novel Coronavirus Disease • Oncology • Pneumonia • Respiratory Diseases • Transplantation

Prospective study on the impact of BEAM versus FEAM conditioning on occurrence of neutropenic enterocolitis and on transplant outcome in lymphoma patients. (PubMed, Front Oncol) - "Carmustine (BCNU), etoposide, cytarabine, and melphalan (BEAM) are a widely used high-dose chemotherapy regimen for autologous stem cell transplantation transplant (ASCT) in lymphoid malignancies. During BCNU shortages, some centers switched to fotemustine-substituted BEAM (FEAM)...The high incidence of NEC and the low mortality is related to a timely US diagnosis and prompt treatment. US knowledge in NEC diagnosis allows to have comparable days of hospitalization of patients NECpos vs. patients NECneg. The cost analysis of NECpos vs. NECneg has been also performed."

Journal • Bone Marrow Transplantation • Gastrointestinal Disorder • Hematological Malignancies • Lymphoma • Oncology • Transplantation

Metabolic models predict fotemustine and the combination of eflornithine/rifamycin and adapalene/cannabidiol for the treatment of gliomas. (PubMed, Brief Bioinform) - "Gliomas are the most common type of malignant brain tumors, with glioblastoma multiforme (GBM) having a median survival of 15 months due to drug resistance and relapse. However, fotemustine and valganciclovir alone and eflornithine and celecoxib in combination with AntiBCs improved the survival compared to AntiBCs in two-arms, phase I/II and higher glioma clinical trials. Our work highlights the potential of metabolic modeling in advancing glioma drug discovery, which accurately predicted metabolic vulnerabilities, repurposable drugs and combinations for the glioma subtypes."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

Nivolumab plus ipilimumab in melanoma patients with asymptomatic brain metastases: 7-year outcomes and quality of life from the multicenter phase III NIBIT-M2 trial. (PubMed, Eur J Cancer) - "With the longest follow-up available to date in melanoma patients with asymptomatic brain metastases, the NIBIT-M2 study continues to show persistent therapeutic efficacy of I ipilimumab plus nivolumab while preserving HRQoL."

HEOR • Journal • P3 data • Brain Cancer • Melanoma • Oncology • Solid Tumor

An attempt to prepare sulfonyl analogues of fotemustine: unexpected rearrangement to sulfamate during nitrosation step. (PubMed, RSC Adv) - "Some attempts to understand this rearrangement reaction were conducted, and particularly the corresponding nitrosoureas analogues could be isolated with good yield. The novel sulfonamidophosphonates as well as their sulfamate derivatives were evaluated for their cytotoxic effect on a panel of tumor cells."

Journal • Oncology

NIBIT-M2: 7-year outcomes and QoL analysis in melanoma patients (YouTube) - "Georgina V. Long...discusses the seven-year efficacy outcomes and health-related quality-of-life (HRQoL) analyses of the Phase III NIBIT-M2 (NCT02460068) trial. The study evaluated the efficacy of fotemustine (Arm A) versus the combination of fotesmustine and ipilimumab (Arm B) or the combination of ipilimumab and nivolumab (Arm C) in patients with metastatic melanoma with brain metastasis."

Interview • Video

Nivolumab plus ipilimumab in melanoma patients with asymptomatic brain metastases: 7-year outcomes and quality of life from the multicenter phase III NIBIT-M2 trial (ESMO 2023) - P3 | "Methods The NIBIT-M2 study recruited melanoma pts with active, untreated, asymptomatic BM from 9 Italian Centers that were randomized (1:1:1) to fotemustine (F) (Arm A), I+F (Arm B), or I+N (Arm C). Conclusions The 7-year results of the NIBIT-M2 study, with the longest follow-up available to date in melanoma pts with asymptomatic BM treated with I+N, continue to show persistent therapeutic efficacy. HRQoL was preserved in all treatment arms and I+N induced a lower decrease in mean functional scales."

Clinical • HEOR • P3 data • Melanoma • Oncology • Solid Tumor