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Objetivos: A anemia falciforme (SCD) é uma doença hereditária causada pela polimerização de hemoglobina falciforme desoxigenada (HbS). Voxelotor é um inibidor de polimerização de HbS aprovado nos EUA e nos EAU para doentes com idade ≥4 anos, e na UE, Grã-Bretanha, Omã e Koweit, em doentes com idade ≥12 anos. O propósito deste estudo foi examinar os padrões de uso de voxelotor em pacientes de 9 instituições nos EUA como parte do Retrospective Real World Oxbryta Data Collection and Analysis Study (RETRO; NCT04930328). Materiais e metodologia: RETRO é um estudo de recolha e análise de dados retrospetivo, multicêntrico e posterior à colocação do produto no mercado. Os doentes elegíveis idade ≥12 anos, diagnosticados com SCD, tinham recebido voxelotor por ≥2 semanas consecutivas e tinham dados laboratoriais e clínicos disponíveis de 1 ano antes e até 1 ano após a primeira dose de voxelotor. Resultados: Foram recolhidos e analisados dados de 216 doentes. A média (SD) da idade dos doentes foi de 33,5 (14,2 anos) e 14,4% dos doentes tinham idade inferior a 18 anos. Um total de 120 doentes (55,6%) eram do sexo feminino, 189 (87,5%) eram afro-americanos ou negros e 199 (92,1%) tinham o genótipo HbSS. Sessenta por cento dos doentes foram tratados com voxelotor por ≥9 meses durante o período de estudo de 12 meses. A maioria dos doentes (86%) teve a prescrição de uma dose inicial de 1.500 mg uma vez ao dia, e 14% tiveram uma prescrição de uma dose inicial abaixo da recomendada na bula. Vinte e três por cento dos doentes tiveram uma modificação de dose iniciada pelo médico. A descontinuação do tratamento foi relatada por 21,8% dos doentes; os motivos incluíram acontecimentos adversos (8,3%) e “outros” (13,5%), que incluíram a perda de seguimento, decisão do médico e retirada do estudo. As análises preliminares de segurança sugerem que não houve evidência que a interrupção ou descontinuação do medicamento tenha levado ao início rápido de acontecimentos adversos (incluindo crises vaso-oclusivas (VOC)), conforme sugerido anteriormente para doentes com SCD grave (Nagalapuram V, Am J Hematol; 2022). Nos 45 doentes (20,8%) que apresentaram VOC após a interrupção ou descontinuação do medicamento, o tempo médio (percentil 25 a 75) para o início de uma VOC foi de 74 (29-138) dias. Dois doentes apresentaram uma VOC dentro de 1 semana após a interrupção ou descontinuação da dose; ambos os acontecimentos foram considerados como não relacionados com o voxelotor pelos investigadores. Discussão: Esses dados estão de acordo com os achados pré-clínicos do voxelotor na reologia eritrocitária após interrupção ou ou descontinuação do tratamento (Kanne CK et al, Front Physiol; 2021). Existem análises em curso para entender melhor os efeitos dos padrões de dosagem de voxelotor em termos de segurança e eficácia. Conclusões: RETRO é o maior estudo multicêntrico para e análise retrospetiva de dados no mundo real de doentes com SCD tratados com voxelotor. A maioria dos doentes não necessitou de modificação da dose ou de descontinuação do tratamento. A descontinuação e a interrupção da dose não foram relacionadas ao aparecimento subsequente de VOCs. Dados sobre padrões de uso de voxelotor no cenário do mundo real podem fornecer informações valiosas sobre práticas de prescrição e dosagem. Financiamento: Pfizer.

Objective: Voxelotor is a first-in-class sickle hemoglobin-polymerization inhibitor that was approved in 2019 by the US Food and Drug Administration for treatment of patients with sickle cell disease (SCD) aged ≥12 years; in 2021, the approval was extended to children with SCD aged 4 to 11 years. Additionally, both the Ministry of Health and Prevention for the United Arab Emirates and the European Commission granted marketing authorization for voxelotor in September 2021 and February 2022, respectively, for treatment of SCD in adults and pediatric patients aged ≥12 years. Thus, additional information on the patient experience with voxelotor would be useful for patients, caregivers, and healthcare professionals alike. The purpose of this study was to conduct semistructured interviews in an effort to understand the experiences and perspectives of voxelotor-treated patients with SCD., Methods: One-time semistructured interviews with adults, adolescents, and children with SCD and their primary caregivers were conducted in the United States. Twenty-three adults and adolescents were recruited across 4 clinical sites, and 10 children-caregiver dyads were recruited from a single site. The interview was designed to elicit patient perspectives on symptomatic changes with voxelotor and the impact of treatment on patients' perceived health-related quality of life. Individual interview transcripts were analyzed using a thematic analytic approach, and concept saturation was assessed in both cohorts., Results: Most patients reported improvements in their SCD symptoms with voxelotor treatment, specifically regarding pain crises, jaundice, and fatigue. Almost all patients experienced improvements in self-reported health-related quality of life with voxelotor treatment., Conclusions: This study provides patient and caregiver perspectives on the symptomatic benefits of voxelotor treatment. These findings not only highlight the benefits of voxelotor treatment in improving symptoms and increasing health-related quality of life across the entire SCD population but also can inform further research on SCD-specific patient-reported outcomes., Competing Interests: Clark Brown is an employee at Global Blood Therapeutics, Inc.; a consultant at Imara and Novo Nordisk; and a recipient of the research funding from Forma Therapeutics, Global Blood Therapeutics, Inc., Imara, and Novartis. Modupe Idowu is on the advisory board at Novartis; on the advisory board and a speaker at Global Blood Therapeutics, Inc.; and a recipient of the research funding from Pfizer Inc., Novartis, Global Blood Therapeutics, Inc., and Forma Therapeutics. Richard Drachtman is a consultant and speaker at Global Blood Therapeutics, Inc. and Agios; a speaker at Jazz Pharmaceuticals; and a consultant at Bluebird Bio. Anne Beaubrun is an employee at Global Blood Therapeutics, Inc. Irene Agodoa and Andy Nguyen are former employees at Global Blood Therapeutics, Inc. Kelly Lipman, Olga Moshkovich, Ryan Murphy, and M. Alex Bellenger are employees at ICON plc. Wally Smith is a consultant at Global Blood Therapeutics, Inc., Novartis, Pfizer Inc., GlycoMimetics, Ironwood, Novo Nordisk, Emmaus Pharmaceuticals, Fera Pharmaceuticals, and Agios Pharmaceuticals and a recipient of the research funding from Global Blood Therapeutics, Inc., NHLBI, PCORI, HRSA, Novartis, Forma Therapeutics, Imara, and Shire., (Copyright © 2023 Clark Brown et al.)

Introduction: Testicular germ cell tumors, particularly nonseminomatous germ cell tumors (NSGCT), comprise the most common solid malignancy in male children and younger adults. While these patients experience excellent survival outcomes, few studies have characterized their survival by age. Thus, we aimed to characterize the relative survival of NSGCT by age, stratifying patients by stage group., Methods: Using the Surveillance Epidemiology and End Results (SEER) database, we divided patients with NSGCT into pediatric patients and adolescents (<19 years), young adults (19-30 years), and older adults (>30 years). Survival analysis, using Cox proportional hazards models and Kaplan Meier curves, described overall and cancer-specific survival (CSS) of each age category for Stage I-III NSGCT by stage group., Results: A total of 14,786 patients met inclusion criteria and comprised the age groups <19 years (N=1,287), 19 to 30 years (N=7,729), and >30 years (N=5,770). Stage group distribution at presentation was similar between each group. Survival analysis demonstrated no differences in cancer-specific survival (CSS) among Stage I or II NSGCT. However, among Stage III tumors, multivariable models noted worse CSS in patients >30 years (HR=3.35 (95%CI: 1.45-7.73), P=0.005) and those 19-30 years (HR=2.28 (95%CI: 0.99-5.21), P=0.053) compared to pediatric and adolescent patients., Conclusions: Younger NSGCT patients experience excellent oncologic outcomes compared to their older counterparts. These survival differences by age group are largely driven by differential survival among Stage III neoplasms. Furthermore, our report lends additional evidence that age is an important prognostic factor in advanced NSGCT, including pediatric and adolescent patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)