Autor: Elliott, Martin - Prolib Integro

Skocz do pozycji: 1.

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Tytuł:: Influence of Surgical Excision on the Survival of Patients With Stage 4 High-Risk Neuroblastoma : a Report From the HR-NBL1/SIOPEN Study
Autorzy:: Laureys, Genevieve
Beck-Popovic, Maja
Malis, Josef
Ruud, Ellen
Rygl, Michal
Avanzini, Stefano
Castel, Victoria
Luksch, Roberto
Monclair, Tom
Sarnacki, Sabine
De Lacerda, Ana
Schroeder, Henrik
Godziński, Jan
Ladenstein, Ruth
Pearson, Andrew
Ash, Shifra
McHugh, Kieran
Valteau-Couanet, Dominique
Balwierz, Walentyna
Rasmussen, Lars
Bysiek, Adam
Metzelder, Martin
Bjornland, Kristin
Squire, Roly
Stenman, Jakob
Cecchetto, Giovanni
Freud, Enrique
Irtan, Sabine
Elliott, Martin
Ambros, Peter
Papadakis, Vassilios
Matthyssens, Lucas
Potschger, Ulrike
Gaze, Mark
Owens, Cormac
Holmes, Keith
Gomez-Chacon, Javier
Joseph, Jean-Marc
Trahair, Toby
Dostawca treści:: Repozytorium Uniwersytetu Jagiellońskiego

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Skocz do pozycji: 3.

Tytuł:: Frequency and prognostic impact of ALK amplifications and mutations in the European Neuroblastoma Study Group (SIOPEN) High-Risk Neuroblastoma Trial (HR-NBL1)
Autorzy:: Popovic-Beck, Maja
Bown, Nick
Font de Mora, Jaime
Noguera, Rosa
Taschner-Mandl, Sabine
Muhlethaler-Mottet, Annick
Laureys, Genevieve
Malis, Josef
Pierron, Gaelle
Kogner, Per
Rossing, Maria
Combaret, Valerie
Chesler, Louis
Castel, Victoria
Luksch, Roberto
Tweddle, Deborah A.
Bellini, Angela
de Preter, Katleen
Ladenstein, Ruth
George, Sally L.
Ambros, Peter F.
Baulande, Sylvain
Beiske, Klaus
Marques, Barbara
Ash, Shifra
Clement, Nathalie
van Roy, Nadine
Valteau-Couanet, Dominique
Balwierz, Walentyna
Schleiermacher, Gudrun
Martinsson, Tommy
Vicha, Ales
Delattre, Olivier
Auger, Nathalie
Jeison, Marta
Morini, Martina
Betts, David R.
Bhalshankar, Jaydutt
Lapouble, Eve
Elliott, Martin
Bernkopf, Marie
Mazzocco, Katia
Potschger, Ulrike
Bernard, Virginie
Jimenez, Irene
Opis:: Purpose: In neuroblastoma (NB), the ALK receptor tyrosine kinase can be constitutively activated through activating point mutations or genomic amplification. We studied ALK genetic alterations in high-risk (HR) patients on the HR-NBL1/SIOPEN trial to determine their frequency, correlation with clinical parameters, and prognostic impact. Materials and Methods: Diagnostic tumor samples were available from 1,092 HR-NBL1/SIOPEN patients to determine ALK amplification status (n = 330), ALK mutational profile (n = 191), or both (n = 571). Results: Genomic ALK amplification (ALKa) was detected in 4.5% of cases (41 out of 901), all except one with MYCN amplification (MNA). ALKa was associated with a significantly poorer overall survival (OS) (5-year OS: ALKa [n = 41] 28% [95% CI, 15 to 42]; no-ALKa [n = 860] 51% [95% CI, 47 to 54], [P < .001]), particularly in cases with metastatic disease. ALK mutations (ALKm) were detected at a clonal level (> 20% mutated allele fraction) in 10% of cases (76 out of 762) and at a subclonal level (mutated allele fraction 0.1%-20%) in 3.9% of patients (30 out of 762), with a strong correlation between the presence of ALKm and MNA (P < .001). Among 571 cases with known ALKa and ALKm status, a statistically significant difference in OS was observed between cases with ALKa or clonal ALKm versus subclonal ALKm or no ALK alterations (5-year OS: ALKa [n = 19], 26% [95% CI, 10 to 47], clonal ALKm [n = 65] 33% [95% CI, 21 to 44], subclonal ALKm (n = 22) 48% [95% CI, 26 to 67], and no alteration [n = 465], 51% [95% CI, 46 to 55], respectively; P = .001). Importantly, in a multivariate model, involvement of more than one metastatic compartment (hazard ratio [HR], 2.87; P < .001), ALKa (HR, 2.38; P = .004), and clonal ALKm (HR, 1.77; P = .001) were independent predictors of poor outcome. Conclusion: Genetic alterations of ALK (clonal mutations and amplifications) in HR-NB are independent predictors of poorer survival. These data provide a rationale for integration of ALK inhibitors in upfront treatment of HR-NB with ALK alterations.
Dostawca treści:: Repozytorium Uniwersytetu Jagiellońskiego

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Tytuł:: Early Single-Site Experience With Transcatheter Tricuspid Valve Replacement
Autorzy:: Vahl, Torsten P.
Hahn, Rebecca T.
Spina, Roberto
Bapat, Vinayak
Akkoc, Deniz
Velagapudi, Poonam
Kodali, Susheel K.
Nazif, Tamim
Leon, Martin
Patel, Amisha
Ng, Vivian
George, Isaac
Elias, Elliott
Kantor, Alex
Khalique, Omar K.
Wu, Isaac
Bartuś, Krzysztof
Dostawca treści:: Repozytorium Uniwersytetu Jagiellońskiego

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Skocz do pozycji: 5.

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Tytuł:: Epcoritamab, a novel, subcutaneous CD3xCD20 bispecific T-cell-engaging antibody, in relapsed or refractory large B-cell lymphoma : dose expansion in a phase I/II trial
Autorzy:: Cheah, Chan Y.
van der Poel, Marjolein
Thieblemont, Catherine
Kim, Tae Min
Cota Stirner, Mariana
Feldman, Tatyana
Kilavuz, Nurgul
Poon, Michelle Limei
Do, Young Rok
Ahmadi, Tahamtan
Jurczak, Wojciech
Phillips, Tycel
Elliott, Brian
Chiu, Christopher
Sacchi, Mariana
Gasiorowski, Robin
Hutchings, Martin
Ghesquieres, Herve
Clausen, Michael Roost
Chen, Menghui
Lugtenburg, Pieternella J.
Lewis, David John
Cunningham, David
Opis:: Purpose: Epcoritamab is a subcutaneously administered CD3xCD20 T-cell–engaging, bispecific antibody that activates T cells, directing them to kill malignant CD20+ B cells. Single-agent epcoritamab previously demonstrated potent antitumor activity in dose escalation across B-cell non-Hodgkin lymphoma subtypes. Patients and Methods: In the dose-expansion cohort of a phase I/II study (ClinicalTrials.gov identifier: NCT03625037), adults with relapsed or refractory CD20+ large B-cell lymphoma and at least two prior therapy lines (including anti-CD20 therapies) received subcutaneous epcoritamab in 28-day cycles (once weekly step-up doses in weeks 1-3 of cycle 1, then full doses once weekly through cycle 3, once every 2 weeks in cycles 4-9, and once every 4 weeks in cycle 10 and thereafter) until disease progression or unacceptable toxicity. The primary end point was overall response rate by the independent review committee. Results: As of January 31, 2022, 157 patients were treated (median age, 64 years [range, 20‐83]; median of three [range, 2-11] prior therapy lines; primary refractory disease: 61.1%; prior chimeric antigen receptor (CAR) T-cell exposure: 38.9%). At a median follow-up of 10.7 months, the overall response rate was 63.1% (95% CI, 55.0 to 70.6) and the complete response rate was 38.9% (95% CI, 31.2 to 46.9). The median duration of response was 12.0 months (among complete responders: not reached). Overall and complete response rates were similar across key prespecified subgroups. The most common treatment-emergent adverse events were cytokine release syndrome (49.7%; grade 1 or 2: 47.1%; grade 3: 2.5%), pyrexia (23.6%), and fatigue (22.9%). Immune effector cell–associated neurotoxicity syndrome occurred in 6.4% of patients with one fatal event. Conclusion: Subcutaneous epcoritamab resulted in deep and durable responses and manageable safety in highly refractory patients with large B-cell lymphoma, including those with prior CAR T-cell exposure.
Dostawca treści:: Repozytorium Uniwersytetu Jagiellońskiego