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Lysosomal acid lipase deficiency (LALD) has two clinical phenotypes: an infantile-onset form - Wolman disease (WD) presented by severe malabsorption, cholestasis, malnutrition, hepatosplenomegaly and early death, and a later-onset form - cholesteryl ester storage disorder (CESD) with hepatosplenomegaly, dyslipidemia, malabsorption and variable disease severity manifestation. Enzyme replacement therapy (ERT) with sebelipase alfa was approved by the Brazilian Health Regulatory Agency (ANVISA) in 2017. We report the deleterious effect of ERT interruption in a CESD patient. Male, 16y, diagnosed at 7y, positive familiar history with mother, grandfather and three siblings affected. He was enrolled in the phase 3 clinical trial from age 9-12y under the 3 mg/Kg dose regimen. Then he enrolled in the post-study donation program under the same dose. Due to personal, importation and supply issues, and the COVID-19 pandemic restrictions, he had a progressive decrease in treatment adherence rate: 68% at 12y, 27% at 13y, 30% at 14y and after that he had an interruption of 1 entire year. At 15y he presented with generalized edema, severe fatigue, tachycardia, was hospitalized, diagnosed low serum iron, albumin and protein, acute anemia (hemoglobin: 6.2 g/dL - normal range of 12,5-13,5), and received blood transfusion. In the next year, still without ERT, he was hospitalized again due to generalized edema, acute anemia (Hemoglobin = 6.9 g/dL) and worsening of hypoalbuminemia and iron deficiency, and received blood transfusion. Although our patient has the CESD phenotype, the ERT interruptions did not worsen the liver involvement nor the dyslipidemia, but caused a severe malabsorption which is classically described in WD phenotype. In conclusion, this case serves as an alert that when ERT is interrupted, there is a rapid clinical deterioration. Acknowledgements: to IGEIM, and Drs Felippe Raphael e Oliveira Previdi and Ana Eduarda Saraiva Pereira Campos for clinical assistance of the patient.
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Introducao: Os canceres sao doencas geneticas cujo fenotipo maligno resulta de uma alteracao que e transmitida da celula alterada para suas celulas filhas, rompendo uma serie de barreiras fisiologicas para perpetuar. Atualmente, o cancer e encarado como um problema de saude publica em nivel global e, como outras doencas de curso menos agudo, o diagnostico e o tratamento do cancer tambem foram afetados pela pandemia de COVID-19 (coronavirus disease). Objetivos: Analisar, atraves dos dados disponiveis publicamente no Departamento de Informatica do Sistema Unico de Saude (DATASUS), dos anos de 2020 e 2021, o impacto da pandemia de COVID-19 no diagnostico de neoplasias malignas no estado da Paraiba e comparar com os mesmos periodos de 2019, ultimo ano antes da pandemia. Material e Metodos: Constituiu-se de estudo transversal e descritivo. A populacao alvo foi de pacientes, de todas as faixas etarias, com diagnostico de neoplasia hematologica, firmado no estado da Paraiba, no periodo de 2019, ano pre-pandemia, e no bienio 2020-2021, anos apos a pandemia de COVID-19. Resultados: Em 2019 a Paraiba registrou 403 novos casos de neoplasias hematologicas, sendo 213 no sexo masculino (52,8%). Os tipos mais comuns foram os linfomas nao-Hodgkin, correspondendo a 28,53%, seguido pelas leucemias (24,56%). Quanto ao estadiamento, a maioria dos diagnosticos foi no estagio II (11,6%), com o campo "Ignorado" correspondendo a 59,8%. O tempo medio entre o diagnostico e o inicio do tratamento foi menor que 30 dias (36,22%). Ja em 2020, o Estado registrou 439 novos casos, sendo 234 no sexo masculino (53,3%). Neste ano, os tipos mais comuns foram novamente os linfomas nao-Hodgkin, correspondendo a 32,11%, seguido pelas leucemias (28,7%). O estadiamento se deu no estagio 1 em sua maioria, correspondendo a 14,57%, com o campo ignorado neste ano tendo atingido a marca de 57,4%. O tempo medio entre o diagnostico e o inicio do tratamento foi menor que 30 dias (34,39%). No segundo ano apos a pandemia, em 2021, a Paraiba registrou 450 novos casos de neoplasias hematologicas, sendo 280 no sexo masculino (62,22%). Neste ano, o tipo mais comum foram as leucemias (32,44%) seguido dos linfomas nao-Hodgkin (29,33%). A maioria dos diagnosticos se deu no estagio III (10,66%) e o tempo medio entre o diagnostico e o inicio do tratamento foi maior que dois meses na maioria dos casos, correspondendo a 42,88%. Discussao: A pandemia de COVID-19 trouxe diversas repercussoes para a area da saude, mais do que aquelas implicadas tao somente pela infeccao que o virus SARS-CoV-2 traz em si, porem nao afetou o numero dos diagnosticos de neoplasias hematologicas no estado da Paraiba. Cabe pontuar que aumentou o tempo entre o diagnostico e o inicio do tratamento, bem como houve mais diagnosticos em estagios mais avancados da doenca, talvez pela realocacao de recursos e infraestrutura redirecionados para atendimento das sindromes respiratorias agudas. Conclusao: Apesar de nao haver impactado no numero de diagnosticos, a pandemia de COVID-19 trouxe impactos prognosticos, com maior tempo ate inicio do tratamento e com diagnosticos em estagios mais avancados de doenca. Tambem cabe destacar a quantidade de dados computados nos campos dados como "Ignorado", "Nao aplica" ou "Outros", o que dificulta a analise fidedigna dos dados epidemiologicos. Copyright © 2022
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SESSION TITLE: COVID-19 Case Report Posters 1 SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: The FDA limits REGEN-COV (Casirivimab/Imdevimab) use to asymptomatic adults at high risk for progression to severe COVID-19 pneumonia or post-exposure prophylaxis. Here, we present a case of compassionate use of REGEN-COV in severe COVID-19 pneumonia. CASE PRESENTATION: A 76-year-old male with a medical history significant for COPD, Rheumatoid arthritis (treated with hydroxychloroquine and low dose steroids), and monoclonal gammopathy of undetermined significance (MGUS) presented with one week of fever, cough, and fatigue. He was febrile to 103 F, with normal oxygen saturation on admission. SARS-CoV-2 rapid molecular PCR was positive. He was started on Levofloxacin, but he did not meet the criteria for administration of dexamethasone, remdesivir, or monoclonal antibody (mAb) therapy. On day one of admission, he became hypoxemic and was subsequently started on dexamethasone and remdesivir. He was given convalescent plasma to address inadequate antibody response to COVID-19 immunization secondary to his chronic immunosuppressed/immunodeficient state. His hypoxemia continued to worsen, requiring high-flow nasal cannula oxygen (HFNC). A regimen of tocilizumab was also initiated. CT chest angiography ruled out pulmonary embolism but revealed diffuse bilateral patchy opacities. His oxygen requirements continued to increase with decreasing ROX index and hence was transferred to the Intensive Care Unit. Repeat PCR for SARS-COV-2 was significant for a high viral load. Approval for compassionate use of REGEN-COV was obtained and administered to the patient. Following administration, his symptoms improved significantly with the transition from HFNC to simple nasal cannula oxygen. Repeat PCR for SARS-CoV-2 also showed a remarkable decline of the viral load. He was transferred back to the medical floors and later to the skilled nursing facility once he was clinically more stable. DISCUSSION: In the United States, REGEN-COV (Casirivimab/Imdevimab) treatment has been approved for emergency use since November 2020. The combination of these two neutralizing immunoglobulin gamma 1 (IgG1) mAb attacks the spike protein of the SARS-CoV-2 virus and has been shown to effectively prevent the progression of symptomatic COVID-19 pneumonia and decrease the high viral load of SARS-CoV-2. It also reduces COVID-19 related hospitalization or death, especially in immunosuppressed patients. Our patient received dexamethasone, remdesivir, tocilizumab, and convalescent plasma as part of conventional COVID-19 treatment with continued worsening of COVID-19 pneumonia. However, the compassionate use of REGEN-COV led to rapid clinical improvement of the patient's symptoms and reduced the SARS-CoV-2 viral load. CONCLUSIONS: Hence, physicians and FDA should consider expanding the use of REGEN-COV mAB therapy to immunosuppressed patients with rapidly worsening COVID-19 pneumonia in adjunct to conventional COVID-19 treatment. Reference #1: Stein D, Oviedo-Orta E, Kampman WA, McGinniss J, Betts G, McDermott M, Holly B, Lancaster JM, Braunstein N, Yancopoulos GD, Weinreich DM. Compassionate Use of REGEN-COV ® in Patients with COVID-19 and Immunodeficiency-Associated Antibody Disorders. Clin Infect Dis. 2021 Dec 31:ciab1059. doi: 10.1093/cid/ciab1059. Epub ahead of print. PMID: 34971385;PMCID: PMC8755381. Reference #2: O'Brien MP, Forleo-Neto E, Musser BJ, Isa F, Chan KC, Sarkar N, Bar KJ, Barnabas RV, Barouch DH, Cohen MS, Hurt CB, Burwen DR, Marovich MA, Hou P, Heirman I, Davis JD, Turner KC, Ramesh D, Mahmood A, Hooper AT, Hamilton JD, Kim Y, Purcell LA, Baum A, Kyratsous CA, Krainson J, Perez-Perez R, Mohseni R, Kowal B, DiCioccio AT, Stahl N, Lipsich L, Braunstein N, Herman G, Yancopoulos GD, Weinreich DM;Covid-19 Phase 3 Prevention Trial Team. Subcutaneous REGEN-COV Antibody Combination to Prevent Covid-19. N Engl J Med. 2021 Sep 23;385(13):1184-1195. doi: 10.1056/NEJMoa2109682. Epub 2021 Aug 4. PMID: 34347950;PMCI : PMC8362593. Reference #3: Weinreich DM, Sivapalasingam S, Norton T, Ali S, Gao H, Bhore R, Xiao J, Hooper AT, Hamilton JD, Musser BJ, Rofail D, Hussein M, Im J, Atmodjo DY, Perry C, Pan C, Mahmood A, Hosain R, Davis JD, Turner KC, Baum A, Kyratsous CA, Kim Y, Cook A, Kampman W, Roque-Guerrero L, Acloque G, Aazami H, Cannon K, Simón-Campos JA, Bocchini JA, Kowal B, DiCioccio AT, Soo Y, Geba GP, Stahl N, Lipsich L, Braunstein N, Herman G, Yancopoulos GD;Trial Investigators. REGEN-COV Antibody Combination and Outcomes in Outpatients with Covid-19. N Engl J Med. 2021 Dec 2;385(23):e81. doi: 10.1056/NEJMoa2108163. Epub 2021 Sep 29. PMID: 34587383;PMCID: PMC8522800. DISCLOSURES: No relevant relationships by Mubashir Ayaz Ahmed No relevant relationships by Shayet Hossain Eshan No relevant relationships by Sami Hussein No relevant relationships by Khalid Hussein No relevant relationships by Kamalnath Sankaran Rajagopalan No relevant relationships by Chenyu Sun
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Background: DT combination has shown efficacy in the adjuvant setting for BRAF-mutated melanoma (BMM) patients (pts) in clinical trials. Previous reports from DESCRIBE-AD resulted in promising overall survival (OS) rates at 12 months. Methods: An observational retrospective study was carried out in 25 GEM sites in Spain. Histologically confirmed and resected BMM pts previously treated with DT according to standard clinical practice in the adjuvant setting were included. Only surgical resection was allowed as a prior treatment to DT. DT discontinuation rate and time to treatment discontinuation were the primary objective. Secondary objectives included safety and efficacy of the combination. Here, we report 3-year results for OS. Results: From 10/2020 to 03/2021, 65 pts were included. Median age was 58 years, 55% were male and 60%, 25%, and 14% had an ECOG PS 0/1/Uk respectively, one patient presented ECOG 3. Allocation of stage IIIA, IIIB and IIIC according to TNM AJCC 7th edition was 29%, 26% and 32%, respectively. There were 3 pts diagnosed at stage I/II but considered of risk, and 2 pts with stage IV but completely resected, all considered for adjuvant DT. Ulceration was present in 40%, Breslow ≥2 mm in 71%, and nodes were microscopically and macroscopically affected in 39% and 22% of pts, respectively. Only 9.2% of pts discontinued DT prematurely due to toxicity and 21.2% had dose reductions to manage toxicity. After a median follow-up of 36.2 m (range: 13-51.1), the overall OS rate at 3-years was 83.5% (95% CI: 74.5-93.5). According to AJCC 7 stage at diagnosis, the 3-years OS rate was 95.2% (95% CI: 86.6-100), 75% (56-100), and 76.8% (60.7-97.2) for stage I-II-IIIA, IIIB, and IIIC-IV respectively. Throughout the study period 11 (16.9%) pts died, of which 10 died due to disease progression and one due to COVID-19 infection. Conclusions: Adjuvant treatment with DT for melanoma achieved good treatment compliance and has proven efficacy in the real world. Adjuvant DT has a clinical impact in survival in line with previous clinical trial COMBI-AD. Editorial acknowledgement: We acknowledge Mfar Clinical Research staff for their assistance in the development of this . Legal entity responsible for the study: Grupo Español Multidisciplinar en Melanoma (GEM). Funding: Grupo Español Multidisciplinar en Melanoma (GEM) as Sponsor with Industry partner NOVARTIS. Disclosure: P. Cerezuela-Fuentes: Financial Interests, Personal, Other, Consultancy, conference,congress attendance/infrastructure: BMS, MSD, Pierre Fabre, Roche, Sanofi, SunPharma. J. Martín-Liberal: Financial Interests, Personal, Other, Lecture fees: Astellas, MSD;Financial Interests, Personal, Other, Lecture fees, advisory fees: Bristol Myers Squibb, Novartis, Pierre Fabre, Pfizer, Roche, Sanofi;Non-Financial Interests, Personal, Member, membership or affiliation: ASCO, ESMO, SEOM, GEM, EORTC, SOGUG, GEIS. L.A. Fernández-Morales: Financial Interests, Personal, Invited Speaker, Speak at sponsored meetings: BMS, MSD, Pierre-Fabre, Roche;Financial Interests, Personal, Other, Speak at sponsored meetings and advisory role: Novartis. J. Medina Martinez: Financial Interests, Personal, Other, Speaker, consultancy or advisory role or similar activity: Novartis, Roche, Pierre Fabre, BMS, MSD, Sanofi. M. Quindós: Financial Interests, Personal, Other, speaker, consultancy and advisory: AstraZeneca, GSK, Merck Sharp & Dohme, Novartis, PharmaMar, Roche, Bristol Myers Squibb, Pierre Fabre;Financial Interests, Institutional, Other, Clinical trials: Merck Sharp & Dohme, Roche, Bristol Myers Squibb. A. García Castaño: Non-Financial Interests, Advisory Role: Bristol, MSD, Novartis. T. Puértolas: Financial Interests, Personal, Invited Speaker, Speaker and advisory role: BMS, Novartis;Financial Interests, Personal, Invited Speaker: Roche, MSD, Sun-Pharma;Financial Interests, Personal, Other, Speaker and advisory role: Pierre-Fabre;Financial Interests, Personal, Advisory Role: Sanofi;Financial Interests, Institutional, Other, Clinical trial: Roche, BMS, Apexi en Inc, Aduro Biotech, Alkermes Inc;Non-Financial Interests, Institutional, Other, congresses inscriptions: Lilly, Sun-Pharma, Novartis, Roche, MSD;Non-Financial Interests, Institutional, Leadership Role, Vocal: GEM (Grupo Español Multidisciplinar de Melanoma);Non-Financial Interests, Institutional, Affiliate: SEOM (Sociedad Española de Oncología Médica), GEM (Grupo Español Multidisciplinar de Melanoma). P. Ayala de Miguel: Financial Interests, Personal, Invited Speaker, Public speaking: Novartis, Merck Sharp & Dohme, Sanofi, Pierre-Fabré. B. Campos: Financial Interests, Personal, Other, Speaker or advisory role: Roche, BMS, Sanofi, Novartis, Pierre-Fabre, Sun Pharma;Financial Interests, Personal, Other, Speaker role: AstraZeneca, Merck, ROVI, Leo Pharma. E. Espinosa: Financial Interests, Personal, Advisory Role, Advisory: BMS, MSD;Financial Interests, Personal, Other, Advisory, educational activities: Novartis;Financial Interests, Personal, Invited Speaker, Advisory, educational activities: Pierre Fabre;Financial Interests, Personal, Funding, Funding for translational investigation: Roche;Non-Financial Interests, Personal, Member, Vicepresident: Grupo Español Multidisciplinario de Melanoma. A. Rodríguez-Lescure: Financial Interests, Personal, Advisory Role: Pfizer, Novartis, ROCHE, AstraZeneca, Daiichi Sankyo, Seagen;Financial Interests, Personal, Invited Speaker, Public speaking: Pierre-Fabre;Financial Interests, Institutional, Research Grant, Grant for Clinical Trials: BMS, Lilly, Roche, Novartis, Amgen, Pzifer, Zimeworks, AstraZeneca, G1 Therapeutics, Bayer. L. Espasa Font: Financial Interests, Personal, Full or part-time Employment: Novartis. G. Belaustegui Ferrández: Financial Interests, Personal, Full or part-time Employment: Novartis. All other authors have declared no conflicts of interest.