Maximilian Julve

All Publications

• A novel granulocyte scoring system for use as a predictive/ prognostic biomarker in patients with renal cell carcinoma (RCC) undergoing treatment with combination immunotherapy Wong, S. N., Julve, M., Charfare, F., Khatib, K., Cheruvu, S., Le, H. L., Larkin, J., Furness, A. ELSEVIER. 2025

  View details for DOI 10.1016/j.annonc.2025.08.3274

  View details for Web of Science ID 001633310200086

• Tumor-infiltrating lymphocyte therapy and the mucosal melanoma treatment landscape. Cancer communications (London, England) Thomas, J., Julve, M., Larkin, J., Furness, A. 2025; 45 (11): 1579-1582

  View details for DOI 10.1002/cac2.70069

  View details for PubMedID 41090413

  View details for PubMedCentralID PMC12629853

• Efficacy of adjuvant therapy in patients with stage IIIA cutaneous melanoma. Annals of oncology : official journal of the European Society for Medical Oncology Grover, P., Lo, S. N., Li, I., Kuijpers, A. M., Kreidieh, F., Williamson, A., Amaral, T., Dimitriou, F., Placzke, J., Olino, K., Vitale, M. G., Saiag, P., Gutzmer, R., Allayous, C., Olofsson Bagge, R., Mattsson, J., Asher, N., Carter, T. J., Meniawy, T. M., Lawless, A. R., Czapla, J. A., Warburton, L., Gaudy-Marqueste, C., Grob, J. J., Collins, R. G., Zhang, E., Kessels, J. I., Neyns, B., Mehmi, I., Hamid, O., Julve, M., Furness, A. J., Margolin, K. A., Lev-Ari, S., Ressler, J. M., Haque, W., Khattak, M. A., Wicky, A., Roberts-Thomson, R., Arance, A., Warrier, G., Schollenberger, M. D., Parente, P., Chatziioannou, E., Lipson, E. J., Michielin, O., Weber, J. S., Hoeller, C., Larkin, J., Atkins, M. B., Essner, R., Johnson, D. B., Sullivan, R. J., Nathan, P., Schachter, J., Lebbe, C., Ascierto, P. A., Kluger, H., Rutkowski, P., Dummer, R., Garbe, C., Lorigan, P. C., Burton, E., Tawbi, H. A., Haanen, J., Carlino, M. S., Menzies, A. M., Long, G. V. 2025; 36 (7): 807-818

  Abstract

  Patients with resected American Joint Committee on Cancer eighth edition (AJCC v8) stage IIIA melanoma have been underrepresented in clinical trials of adjuvant drug therapy. The benefit of adjuvant targeted therapy and immunotherapy in this population is unclear.In this multicentre, retrospective study, patients with stage IIIA melanoma (AJCC v8) who received adjuvant pembrolizumab or nivolumab [anti-programmed cell death protein 1 (PD-1)], BRAF/MEK-targeted therapy dabrafenib + trametinib (TT) or no adjuvant treatment [observation (OBS)] were included. Recurrence-free survival (RFS), distant metastasis-free survival (DMFS) and toxicity rates were examined.A total of 628 patients from 34 centres across Australia, Europe and the United States were identified-256 in anti-PD-1, 80 in TT and 292 in OBS. The median follow-up was 2.6 years (interquartile range 1.6-3.4 years). The presence of some key poor prognostic variables was significantly higher in anti-PD-1 compared with OBS. The 2-year RFS was 79.3% [95% confidence interval (CI) 74.1% to 84.8%] for anti-PD-1, 98.6% (95% CI 96.0% to 100%) for TT and 84.3% (95% CI 79.9% to 89.0%) for OBS. The 2-year DMFS was 88.4% (95% CI 84.3% to 92.8%) in anti-PD-1, 100% in TT and 91.1% (95% CI 87.7% to 94.7%) in OBS. Higher Breslow thickness and higher mitotic rate were associated with higher risk of recurrence in anti-PD-1 and OBS (P < 0.05). Rates of ≥grade 3 toxicities were 10.9% with anti-PD-1 and 17.5% with TT; discontinuation due to toxicity occurred in 13.3% and 21.2%, respectively. Rates of unresolved toxicity at last follow-up were 26.9% in the anti-PD-1 group and 12.5% in the TT group.Stage IIIA melanoma has a modest risk of recurrence. Adjuvant anti-PD-1 did not significantly improve RFS or DMFS compared with OBS alone. Adjuvant TT appears promising over anti-PD-1 or OBS. Outcomes after adjuvant therapy in this population needs further study in larger datasets with longer follow-up or prospective randomised trials.

  View details for DOI 10.1016/j.annonc.2025.03.021

  View details for PubMedID 40204154

• Solid tumour cellular therapy - principles of toxicity management. Immuno-oncology technology Julve, M., Wong, Y. N., Lim, K. H., Furness, A. J. 2025; 25: 100737

  Abstract

  Following the Food and Drug Administration (FDA) approval of lifileucel and afami-cel for patients with advanced melanoma and synovial sarcoma, respectively, there is a need for improved understanding and guidance regarding the management of toxicity associated with adoptive cellular therapies (ACTs) for solid tumours. Further approvals are expected in coming years, with toxicity management representing a significant consideration for centres looking to implement such advanced therapy medicinal products. Importantly, first-generation tumour-infiltrating lymphocyte therapies are associated with unique toxicities compared with gene-modified T-cell therapies such as chimeric antigen receptor T-cell therapy (CAR T) and T-cell receptor-modified therapy (TCR T), presenting novel challenges for treating healthcare professionals. Extrapolating from experience with CAR T in the field of haemato-oncology, coupled with the historical use of high-dose interleukin-2 in solid tumour therapeutic regimens and more recently lifileucel and afami-cel, has led to the development of core principles for managing toxicity, which is discussed here. Looking to the future, a rapidly developing field with next-generation ACT products, a basic knowledge of such core principles will be an important foundation for healthcare professionals working in this space.

  View details for DOI 10.1016/j.iotech.2024.100737

  View details for PubMedID 40236329

  View details for PubMedCentralID PMC11997557

• Development of a novel granulocyte scoring system for use as a predictive/prognostic biomarker in patients with advanced melanoma undergoing treatment with combination immunotherapy Julve, M., Wong, Y., Riobo, M., Garitaonaindia, Y., Rosero, D. I., Needham, J., Soto, J., Beland, C., Ha Mo Linh Le, Larkin, J., Furness, A. J. S. LIPPINCOTT WILLIAMS & WILKINS. 2024

  View details for Web of Science ID 001275557402239

• Lifileucel: the first cellular therapy approved for solid tumours. Trends in cancer Julve, M., Lythgoe, M. P., Larkin, J., Furness, A. J. 2024; 10 (6): 475-477

  Abstract

  The US Food and Drug Administration (FDA) approval of lifileucel, for advanced melanoma, represents the first cellular therapy to reach the clinic for solid cancers. Here, we summarise this landmark approval, consider the associated regulatory pathway, and evaluate the challenges that remain to ensure effective implementation of this advanced 'living' therapy.

  View details for DOI 10.1016/j.trecan.2024.04.003

  View details for PubMedID 38724322

• Gene of the month: cancer testis antigen gene 1b (NY-ESO-1). Journal of clinical pathology Julve, M., Kennedy, O., Frampton, A. E., Bagwan, I., Lythgoe, M. P. 2023; 77 (1): 1-7

  Abstract

  Cancer testis antigen gene 1B (CTAG1B) and its associated gene product; New York oesophageal squamous carcinoma 1 (NY-ESO-1), represent a unique and promising target for cancer immunotherapy. As a member of the cancer testis antigen family (CTA), the protein's restricted expression pattern and ability to elicit spontaneous humoural and cellular immune responses has resulted in a plethora of novel modalities and approaches attempting to harness its immunotherapeutic anti-cancer potential. Here, we discuss the structure and function of CTAG1B/NY-ESO-1 in both health and disease, immunohistochemical detection, as well as the most promising advances in the development of associated anti-cancer therapies. From cancer vaccines to engineered cellular therapy approaches, a multitude of immunotherapies targeting CTA's are coming to the forefront of oncology. Although the efficacy of such approaches have yet to provide convincing evidence of durable response, early phase clinical trial data has resulted in some exciting findings which will have significant potential to act as a platform for future practice changing technologies.

  View details for DOI 10.1136/jcp-2023-209053

  View details for PubMedID 37857483

• Advances in the development of tumor-infiltrating lymphocyte therapy for advanced melanoma. Expert opinion on biological therapy Julve, M., Furness, A. J. 2023; 23 (4): 319-323

  View details for DOI 10.1080/14712598.2023.2193290

  View details for PubMedID 36932721

• United Kingdom real-world experience of sotorasib in KRAS G12C mutant non-small cell lung cancer: A British thoracic oncology group review Julve, M., Kennedy, O., Lindsay, C., Walters-Davies, R., Button, M. R., Steele, N., McGeogh, A., Georgiou, A., Goranov, B., Farrugia, D., Gorf, L., Remer, M., Shah, R., Baijal, S., Gennatas, S., Geldart, T., Daniels, E., Watts, L., Greystoke, A., Newsom-Davis, T. ELSEVIER. 2022: S1061-S1062

  View details for Web of Science ID 000866211601380

• Immunotherapy of sarcomas with modified T cells. Current opinion in oncology Mahalingam, P., Julve, M., Huang, P., Furness, A. J., Pollack, S. M., Jones, R. L. 2022; 34 (4): 362-370

  Abstract

  To summarize the development of modified T-cell therapies in sarcomas and discuss relevant published and ongoing clinical trials to date.Numerous clinical trials are underway evaluating tumor-specific chimeric antigen receptor T cells and high affinity T-cell receptor (TCR)-transduced T cells in sarcomas. Notably, translocation-dependent synovial sarcoma and myxoid/round cell liposarcoma are the subject of several phase II trials evaluating TCRs targeting cancer testis antigens New York esophageal squamous cell carcinoma-1 (NY-ESO-1) and melanoma antigen-A4 (MAGE A4), and response rates of up to 60% have been observed for NY-ESO-1 directed, modified T cells in synovial sarcoma. Challenges posed by modified T-cell therapy include limitations conferred by HLA-restriction, non-immunogenic tumor microenvironments (TME), aggressive lymphodepletion and immune-mediated toxicities restricting coinfusion of cytokines.Cellular therapy to augment the adaptive immune response through delivery of modified T cells is an area of novel therapeutic development in sarcomas where a reliably expressed, ubiquitous target antigen can be identified. Therapeutic tools to improve the specificity, signaling, proliferation and persistence of modified TCRs and augment clinical responses through safe manipulation of the sarcoma TME will be necessary to harness the full potential of this approach.

  View details for DOI 10.1097/CCO.0000000000000843

  View details for PubMedID 35837706

• Disparity of Race Reporting in FDA Drug Approvals for Urinary System Cancers from 2006 to 2021. BJU international Glover, M., Hui, G., Chiang, R., Savage, P., Krell, J., Julve, M., Grivas, P., Lythgoe, M., Khaki, A. R. 2021

  Abstract

  BACKGROUND: Significant racial disparity exists in urinary system cancers (urothelial carcinoma [UC] and renal cell carcinoma [RCC]), in terms of epidemiology, access to therapy and outcomes. We analyzed racial diversity and race reporting in FDA drug registration trials for UC and RCC.METHOD: All FDA pivotal registration trials between 2006-2021 for both UC and RCC were identified. The trials were analyzed to check for compliance with current FDA recommendations for race reporting. Additional information on participant recruitment and race was obtained to assess representation based on cancer type.RESULTS: From 2006-2021 there were 30 new drug registrations for the management of urinary systems cancers, of which 16 in RCC and 14 in UC. Overall, 70% of these trials reported data on racial representation, however, only 43% reported data stratified into five categories as recommended by the FDA.CONCLUSION: We found a significant under-representation of non-white participants in FDA drug registration clinical trials in UC and RCC. Race reporting is inconsistent and FDA guidelines are not being universally followed. Considering the disproportionate disease burden in UC and RCC, clinical trials should prioritize recruiting a diverse population of participants.

  View details for DOI 10.1111/bju.15629

  View details for PubMedID 34748278

• Pleomorphic lung carcinoma - a rare response to a rare tumour Clark, J., Murphy, R., Dell, E., Julve, M., Januszewski, A., Popat, S., Newsom-Davis, T. ELSEVIER IRELAND LTD. 2021: S76

  View details for Web of Science ID 000657005700185

• Advances in cyclin-dependent kinase inhibitors for the treatment of melanoma. Expert opinion on pharmacotherapy Julve, M., Clark, J. J., Lythgoe, M. P. 2021; 22 (3): 351-361

  Abstract

  Introduction: Despite the recent advances in the treatment of malignant melanoma with immunotherapy and BRAF/MEK targeted agents, advanced disease still beholds a poor prognosis for a significant proportion of patients. Cyclin-dependent kinase (CDK) inhibitors have been investigated as novel melanoma therapeutics throughout a range of phase 1 and 2 trials, as single agents and in combination with established treatments. Areas covered: This article summarizes the rationale for, and development of CDK inhibitors in melanoma, with their evolution from pan-CDK inhibitors to highly specific agents, throughout clinical trials and finally their potential future use. Expert opinion: Whilst CDK inhibitors have been practice changing in breast cancer management, their efficacy is yet to be proven in melanoma. Combination with BRAF/MEK inhibitors has been hindered by dose-limiting toxicities, but their role may yet to be found within the spectrum of biomarker-derived personalized melanoma management. The effect that CDK inhibitors can have as an adjunct to immunotherapy also remains to be seen.

  View details for DOI 10.1080/14656566.2020.1828348

  View details for PubMedID 33030382

• Rare case of adult pancreatoblastoma. BMJ case reports Morrissey, G., Cohen, P., Julve, M. 2020; 13 (4)

  View details for DOI 10.1136/bcr-2019-233884

  View details for PubMedID 32265211

  View details for PubMedCentralID PMC7244274

• Neurotoxicity from immune-checkpoint inhibition in the treatment of melanoma: a single centre experience and review of the literature. Annals of oncology : official journal of the European Society for Medical Oncology Spain, L., Walls, G., Julve, M., O'Meara, K., Schmid, T., Kalaitzaki, E., Turajlic, S., Gore, M., Rees, J., Larkin, J. 2017; 28 (2): 377-385

  Abstract

  Treatment with immune checkpoint inhibitors (ICPi) has greatly improved survival for patients with advanced melanoma in recent years. Anti-CTLA-4 and anti-PD1 antibodies have been approved following large Phase III trials. Immune-related neurological toxicity of varying severity has been reported in the literature. The cumulative incidence of neurotoxicity among ipilimumab, nivolumab and pembrolizumab is reported as <1% in published clinical trials. We aimed to identify the incidence of neurotoxicity in our institution across anti-CTLA4 and anti-PD-1 antibodies, including the combination of ipilimumab with nivolumab. We also review the existing literature and propose an investigation and management algorithm.All patients with advanced melanoma treated with ipilimumab, nivolumab, pembrolizumab or the combination of ipilimumab and nivolumab (ipi + nivo), managed at the Royal Marsden Hospital between September 2010 and December 2015, including patients on (published) clinical trials were included. Medical records for each patient were reviewed and information on neurotoxicity recorded. A systematic search strategy was performed to collate existing reports of neurological toxicity.In total, 413 immunotherapy treatment episodes in 352 patients were included, with median follow-up of 26.7 months. Ten cases of neurotoxicity were recorded, affecting 2.8% of patients overall, ranging from grade 1 to 4, affecting both central and peripheral nervous systems. A rate of 14% was noted with ipi + nivo. Three of five patients commenced on corticosteroids responded to these. Six patients had made a full recovery at the time of reporting. A favorable radiological response was found in 7 of the 10 cases. Unusual presentations are described in detail.Neurological toxicity is not uncommon, and may be more frequent in patients treated with combination ipi + nivo. Patterns of presentation and response to treatment are varied. A prompt and considered approach is required to optimize outcomes in this group of patients.

  View details for DOI 10.1093/annonc/mdw558

  View details for PubMedID 28426103

• Combination dabrafenib and trametinib in the management of advanced melanoma with BRAFV600 mutations. Expert opinion on pharmacotherapy Spain, L., Julve, M., Larkin, J. 2016; 17 (7): 1031-8

  Abstract

  In the 40-50% of advanced melanoma patients with tumors harboring BRAF V600E and V600 K mutations, BRAF inhibitors such as dabrafenib are a highly effective treatment. However, most patients develop resistance after several months on treatment. The addition of a MEK inhibitor, such as trametinib, to BRAF inhibition mitigates one key pathway of resistance, further increasing response rates and improving survival.This article summarizes the mechanism of action of the combination of dabrafenib and trametinib, its evolution through Phase I, II and III clinical trials and discusses its current use in the management of patients with advanced melanoma.Combination therapy with dabrafenib and trametinib improves response rate, progression-free survival and overall survival when compared to dabrafenib or vemurafenib alone. The addition of trametinib to dabrafenib changes the adverse event profile, making hyperkeratosis and cutaneous squamous cell carcinomas less common but side effects such as fever and nausea more common. How dabrafenib/trametinib is best sequenced with other effective treatments such as immune checkpoint blockade remains uncertain.

  View details for DOI 10.1517/14656566.2016.1168805

  View details for PubMedID 27027150

• Bilateral extraocular muscle (EOM) metastases from adenocarcinoma of the gastro-oesophageal junction (GOJ). BMJ case reports Julve, M., Maviki, M., Gillmore, R. 2014; 2014

  View details for DOI 10.1136/bcr-2014-205368

  View details for PubMedID 25115784

  View details for PubMedCentralID PMC4139542