MIGLIOR ARTICOLO DEL MESE CON PRIMO AUTORE ITALIANO

“GD2-CART01 for Relapsed or Refractory High-Risk Neuroblastoma”

F. Del Bufalo, B. De Angelis, I. Caruana, G. Del Baldo, M.A. De Ioris, A. Serra, A. Mastronuzzi, M.G. Cefalo, D. Pagliara, M. Amicucci, G. Li Pira, G. Leone, V. Bertaina, M. Sinibaldi, S. Di Cecca, M. Guercio, Z. Abbaszadeh, L. Iaffaldano, M. Gunetti, S. Iacovelli, R. Bugianesi, S. Macchia, M. Algeri, P. Merli, F. Galaverna, R. Abbas, M.C. Garganese, M.F. Villani, G.S. Colafati, F. Bonetti, M. Rabusin, K. Perruccio, V. Folsi, C. Quintarelli, and F. Locatelli, for the Precision Medicine Team–IRCCS Ospedale Pediatrico Bambino Gesù*

N Engl J Med 2023;388:1284-95. DOI: 10.1056/NEJMoa2210859 GD2-CART01 for Relapsed or Refractory High-Risk Neuroblastoma | NEJM

Selezionato dal lettore: Valentina Dortucci

MOTIVATION: Neuroblastoma is the most common extracranial solid tumor in children, and almost half the patients have high-risk disease at diagnosis. Since neuroblastoma cells express high levels of disialoganglioside GD2, this phase 1–2 clinical trial aims to assess the feasibility and safety of GD2-CART01 in patients who had relapsed disease or who had had persistent or progressive disease during first-line treatment (consisted of an induction phase involving intensive chemotherapy, surgery, high-dose chemotherapy with reinfusion of autologous stem cells, radiotherapy, differentiating treatment with isotretinoin, and immunotherapy with the anti-GD2 monoclonal antibody). The first disease assessment was performed in every patient at week 6 after GD2-CART01 infusion by both radiologic (CT and MIBG scans) and magnetic resonance images and SIOPEN scores, evaluated in a blinded fashion. In one third of patients there was a complete response that was maintained in 56% of these patients with a median follow-up of 1.7 years. Their 3-year overall survival was 66% while among children who received the recommended dose (that is 10×106 CAR-positive T cells per kilogram) this percentage was 60%. Among the patients who received additional infusions, the authors observed three complete responses and three partial responses. The only variable associated with lower event-free survival was high disease burden. Although manageable, the side-effect profile of this type of immunotherapy is not negligible: cytokine release syndrome as well as hematologic toxic effects were relevant adverse event in most patients, reversible in all cases; none had central neurotoxic effects. These findings indicate that GD2-CART01 has therapeutic potential against high-risk refractory or relapsed neuroblastoma, but other trials are needed to assess the role of GD2- CART01 in the multimodal treatment of high-risk neuroblastoma.

MIGLIOR ARTICOLO IN ASSOLUTO

“Prediction of Longitudinal Cognitive Decline in Preclinical Alzheimer Disease Using Plasma Biomarkers”

Niklas Mattsson-Carlgren, Gemma Salvadó, Nicholas J. Ashton, et al.

Jama Neurology https://jamanetwork.com/journals/jamaneurology/fullarticle/2801289

Selezionato dal lettore: Ilaria Quartesan

MOTIVATION: The importance of the presymptomatic or preclinical stage of Alzheimer's Disease (AD) has been increasingly recognized in recent years. It has become crucial to identify and initiate disease-modifying treatment in individuals who test positive for β-amyloid (Aβ) but do not yet show cognitive impairment. In line with this, this prospective population-based prognostic study was conducted to investigate plasma biomarkers that could serve as valuable tools alongside cerebrospinal fluid (CSF) or positron emission tomography (PET) biomarkers in clinical trials of disease-modifying treatments. The study drew upon data from two preclinical AD cohort studies, namely the BioFINDER-1 and WRAP cohorts, and focused on 171 cognitively unimpaired participants who exhibited evidence of β-amyloid (Aβ) positivity in their CSF or PET scans. The researchers examined a range of plasma biomarkers associated with AD pathology, including P-tau181, P-tau217, NfL (neurofilament light chain), Aβ42, and t-tau The findings showed that plasmàòa P-tau217 and CSF P-tau217 were the strongest predictors for both mPACC and MMSE scores. This indicates that plasma P-tau217 holds promise as a dependable predictor of cognitive decline during the preclinical stage of AD. The solid methodology employed in this study, including the use of well-characterized cohorts, rigorous statistical analyses, and validation of findings, strengthens the reliability and generalizability of the results, which have important implications for both research and clinical practice in the field of AD. They provide insights into the potential use of plasma P-tau217 as a prognostic marker for cognitive decline in preclinical AD and highlight the importance of considering this biomarker in the design of future clinical trials and the development of personalized treatment approaches for AD patients.