Clinical and pathological characteristics of immune-mediated liver injury caused by immune checkpoint inhibitors / 中华内科杂志

Objective: Cancer immunotherapy can lead to various side effects, termed immune-related adverse events (irAE). This study summarized and analyzed the clinical and pathological characteristics of immune-mediated liver injury caused by immune checkpoint inhibitors (ILICI). Methods: This is a retrospective case series study involving 11 patients diagnosed with ILICI at the Peking Union Medical College Hospital from November 2019 to November 2021. Patient demographic information and clinical data, including gender, age, ILICI onset, clinical and radiological manifestations, pathological features, treatment, and resumption of ICI were retrospectively collected and analyzed. Results: The patients were primarily males (9/11) with a median age of 65 (range: 32-73) years. ICI mainly resulted in either partial remission (4/11) or stable disease (3/11). ILICI occurred after a median of two cycles of anti-programmed cell death-1 (PD-1) therapy, with a median time from the initial and last anti-PD-1 therapy to ILICI onset of 57 days and 17 days, respectively. ILICI was mostly severe (3/11) or very severe (6/11). While the clinical and radiological manifestations were non-specific, the pathological features were active lobular hepatitis and portal inflammation, with prominent CD8+T lymphocyte infiltration. The basic treatment was hepatoprotective drugs (10/11). Glucocorticoids were used as the primary therapy (9/11) but were ineffective in 4 of 9 cases. Of these, 3 of 9 cases received combined treatment with mycophenolate mofetil (MMF), only one of whom achieved remission. By the end of the study, 2 of 11 cases had resumed ICI and neither had experienced an ILICI relapse. Conclusion: The ILICI patients in this study had a corresponding history of ICI treatment and pathological features. The main treatment included hepatoprotective drugs and glucocorticoids. Immunosuppressive drugs were added for some cases but had poor efficacy.

Evaluation of Efficacy and Prognosis Analysis of Stage III-IV SMARCA4-deficient Non-small Cell Lung Cancer Treated by PD-1 Immune Checkpoint Inhibitors plus Chemotherapy and Chemotherapy / 中国肺癌杂志

BACKGROUND@#The SMARCA4 mutation has been shown to account for at least 10% of non-small cell lung cancer (NSCLC). In the present, conventional radiotherapy and targeted therapy are difficult to improve outcomes due to the highly aggressive and refractory nature of SMARCA4-deficient NSCLC (SMARCA4-DNSCLC) and the absence of sensitive site mutations for targeted drug therapy, and chemotherapy combined with or without immunotherapy is the main treatment. Effective SMARCA4-DNSCLC therapeutic options, however, are still debatable. Our study aimed to investigate the efficacy and prognosis of programmed cell death 1 (PD-1) immune checkpoint inhibitors (ICIs) in combination with chemotherapy and chemotherapy in patients with stage III-IV SMARCA4-DNSCLC.@*METHODS@#46 patients with stage III-IV SMARCA4-DNSCLC were divided into two groups based on their treatment regimen: the chemotherapy group and the PD-1 ICIs plus chemotherapy group, and their clinical data were retrospectively analyzed. Efficacy assessment and survival analysis were performed in both groups, and the influencing factors for prognosis were explored for patients with SMARCA4-DNSCLC.@*RESULTS@#Male smokers are more likely to develop SMARCA4-DNSCLC. There was no significant difference in the objective response rate (76.5% vs 69.0%, P=0.836) between chemotherapy and the PD-1 ICIs plus chemotherapy or the disease control rate (100.0% vs 89.7%, P=0.286). The one-year overall survival rate in the group with PD-1 ICIs plus chemotherapy was 62.7%, and that of the chemotherapy group was 46.0%. The difference in median progression-free survival (PFS) between the PD-1 ICIs plus chemotherapy group and the chemotherapy group was statistically significant (9.3 mon vs 6.1 mon, P=0.048). The results of Cox regression analysis showed that treatment regimen and smoking history were independent influencing factors of PFS in patients with stage III-IV SMARCA4-DNSCLC, and family history was an individual influencing factor of overall survival in patients with stage III-IV SMARCA4-DNSCLC.@*CONCLUSIONS@#Treatment regimen may be a prognostic factor for patients with SMARCA4-DNSCLC, and patients with PD-1 ICIs plus chemotherapy may have a better prognosis.

A Real-world Study on the Incidence and Outcome of Immune-related Adverse Events in Lung Cancer Patients / 中国肺癌杂志

BACKGROUND@#Immune-related adverse events (irAEs) are commonly occurred in patients treated with immune checkpoint inhibitors. However, evidence of irAEs derived from the Chinese population is relatively lacking. The aim of this study was to investigate the incidence and outcomes of irAEs in Chinese patients with lung cancer after receiving immune checkpoint inhibitors (ICIs).@*METHODS@#Clinical and follow-up data from lung cancer patients who received at least one time of ICIs from January 2018 to September 2021 at Huadong Hospital, Fudan University were included. Statistical descriptions and Kaplan-Meier method were used to analyze the overall incidence of irAEs, as well as the incidence and outcomes of each type of irAEs.@*RESULTS@#135 patients were included in the study. 106 patients (78.5%) presented at least one type of irAEs, and the median time to first irAEs onset was 28 d. Most irAEs occurred at early time after treatment, and most irAEs were mild-moderate and reversible. 57 patients (42.2%) died at the study cutoff. The mortality rate of severe irAEs was 12.6% (n=17), and among them 7 patients (41.2%) died of pneumonitis. The median progression-free survival (PFS) and overall survival (OS) time of the total population was 505 d (95%CI: 352-658) and 625 d (95%CI: 491-759), respectively. Patients who presented any irAEs achieved a longer PFS than those who did not (median PFS: 533 d vs 179 d, P=0.037, HR=0.57), while patients who presented skin toxicities achieved a longer OS than patients who did not (median OS: 797 d vs 469 d, P=0.006, HR=0.70).@*CONCLUSIONS@#In real-world settings, irAEs in lung cancer patients were commonly observed, with pneumonitis as the most common fatal irAEs. In addition, patients who presented any irAEs may tend to achieve a longer PFS.

Immune-Related Pancreatitis Caused by Immune Checkpoint Inhibitor Nivolumab:Report of One Case / 中国医学科学院学报

In recent years,great progress has been achieved in the application of immune checkpoint inhibitors (ICI) in tumor immunotherapy.However,a variety of adverse reactions induced by ICI have been reported.Despite the high overall incidence of adverse reactions caused by ICI,some adverse reactions,such as immune-related pancreatitis,are rare in clinical practice.In this paper,a case of immune-related pancreatitis after treatment of advanced gastric cancer with nivolumab was identified.We analyzed the cause,treatment,incidence,and risk factors of the adverse reaction,aiming to improve the clinical diagnosis,treatment,and safe medication of rare adverse reactions associated with ICI.

Cetoacidosis diabética como debut de diabetes mellitus inmunomediada en paciente en tratamiento con inhibidores de checkpoint / Diabetic ketoacidosis as debut of immune-mediated diabetes mellitus in a patient in treatment with immune checkpoint inhibitors

Los inhibidores de checkpoint (ICP) son anticuerpos usados en inmunoterapia contra el cáncer. Uno de sus blancos de acción es el receptor de muerte celular programada-1 (PD-1), el cual es importante para mantener la tolerancia inmunitaria. Sin embargo, este mecanismo se asocia a riesgo de eventos adversos relacionados a la inmunidad que pueden afectar a múltiples órganos incluyendo el sistema endocrino. Se describe el caso inhabitual de un paciente que a los 18 meses de terapia con ICP debutó con cetoacidosis diabética (CAD).

Immune checkpoint inhibitors consist in antibodies used in immunotherapy against cancer. One of their targets is the programmed cell death-1 (PD-1) receptor, which is important in maintaining self-tolerance. However, this mechanism is associated with a risk for immune-related adverse events potentially affecting multiple organs, including the endocrine system. We describe the unusual case of a patient who, after 18 months of treatment with an immune checkpoint inhibitor, debuted with diabetic ketoacidosis

Progress of Neoadjuvant Immunotherapy for Non-small Cell Lung Cancer / 中国肺癌杂志

Neoadjuvant immunotherapy, including neoadjuvant single- or dual-drug immunotherapy or combined immunotherapy with chemotherapy or radiotherapy, has witnessed a rapid development in non-small cell lung cancer. Clinical trials exhibited the encouraging pathological responses and certain clinical benefits in selected patients, with tolerable toxicity. Nivolumab with chemotherapy has been approved by Food and Drug Administration (FDA) as the first immunotherapy-based treatment for non-small cell lung cancer in the neoadjuvant treatment setting. There is the need for further evaluation of long-term efficacy, side effects or surgical issues for neoadjuvant immunotherapy in non-small cell lung cancer.
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Current Progress and Future Developments of Antibody Drug Conjugates in Lung Cancer / 中国肺癌杂志

Antibody drug conjugates (ADCs) are a novel class of anti-cancer drugs, which combined the specificity of monoclonal antibodies with the cytotoxic palyload via the linkers. Many ADCs have not only verified impressive activity in a variety of cancers, including breast cancer and hematological system tumors, but also in lung cancer. The aim of this study was to provide informations for practice by summarizing the mechanism of action, clinical application and problems and challenges of ADCs.
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Preliminary Study on Screening and Identification of Lewis a Antigen Mimic Epitope in Alpaca Phage Display Nanobody Library / 中国实验血液学杂志

OBJECTIVE@#To establish a new method for synthesizing Lewis blood group antigens, that is, the mimotopes of Lewis blood group antigens were screened by using an alpaca phage display nanobody library.@*METHODS@#We selected mimotopes of the Lewis a (lea) antigen by affinity panning of an alpaca phage display nanobody library using a monoclonal anti-lea antibody. Enzyme-linked immunosorbent assay (ELISA) was used to test the affinity of the positive clones for the monoclonal anti-lea antibody, and the high-affinity positive clones were selected for sequencing and synthesis. Finally, the sensitivity, specificity and reactivity of the synthesized lea mimotope in clinical samples were verified by ELISA.@*RESULTS@#A total of 96 phage clones were randomly selected, and 24 were positive. Fourteen positive clones with the highest affinity were selected for sequencing. The result showed that there were 5 different sequences, among which 3 sequences with the highest frequency, largest difference and highest affinity were selected for expression and synthesis. The sensitivity and specificity of lea mimic antigen by ELISA showed that, the minimum detection limit of gel microcolumn assay (GMA) and ELISA method were 25 times different, and the lea mimic antigen had no cross reacted with the other five unrelated monoclonal antibodies(P<0.001). Finally, 30 clinical plasma samples were analyzed. The mean absorbance of the 15 positive plasma samples was significantly higher than that of the 15 negative plasma samples (P=0.02). However, the positive signal values of the clinical samples were much lower than those of the monoclonal antibodies.@*CONCLUSION@#A new method of screening lea mimic antigen by using alpaca phage nanoantibody library has been established, which is expected to realize the screening of lea mimotopes, thus realizing the application of high-sensitivity detection methods such as ELISA and chemiluminescence in blood group antibody identification.

Cabozantinibe ou nivolumabe para o tratamento de segunda linha para pacientes com carcinoma de células renais metastático / Cabozantinib or nivolumabe for second-line treatment for patients with metastatic renal cell carcinoma

Este documento é uma versão resumida do relatório técnico da Comissão Nacional de Incorporação de Tecnologias no Sistema Único de Saúde ­ Conitec e foi elaborado numa linguagem simples, de fácil compreensão, para estimular a participação da sociedade no processo de Avaliação de Tecnologias em Saúde (ATS) que antecede a incorporação, exclusão ou alteração de medicamentos, produtos e procedimentos utilizados no SUS. As recomendações da Comissão são submetidas à consulta pública pelo prazo de 20 dias. Após analisar as contribuições recebidas na consulta pública, a Conitec emite a recomendação final, que pode ser a favor ou contra a incorporação, exclusão ou alteração da tecnologia analisada. A recomendação final é, então, encaminhada ao Secretário de Ciência, Tecnologia, Inovação e Insumos Estratégicos em Saúde do Ministério da Saúde -SCTIE/MS, que decide sobre quais tecnologias em saúde serão disponibilizadas no SUS

Cabozantinibe ou nivolumabe para o tratamento de segunda linha para pacientes com carcinoma de células renais metastático / Cabozantinib or nivolumabe for second-line treatment for patients with metastatic renal cell carcinoma

Relatório técnico com Leis que estabelece que a incorporação, a exclusão ou a alteração de novos medicamentos, produtos e procedimentos, bem como a constituição ou alteração de protocolo clínico ou de diretriz terapêutica são atribuições do Ministério da Saúde (MS). A estrutura de funcionamento da Conitec é composta por Plenário e Secretaria-Executiva. A gestão e a coordenação das atividades da Conitec, bem como a emissão do relatório de recomendação sobre as tecnologias analisadas são de responsabilidade da Secretaria-Executiva ­ exercida pelo Departamento de Gestão e Incorporação de Tecnologias e Inovação em Saúde (DGITIS/SCTIE/MS).

Tratamiento preventivo en migraña: anticuerpos monoclonales contra la vía del péptido relacionado con el gen de la calcitonina / Migraine preventive treatment: monoclonal antibodies against calcitonine gene related peptide

Resumen La migraña es un trastorno muy prevalente que afecta a alrededor del 15% de los sujetos adultos. Es clasificada por la Organización Mundial de la Saludentre los primeros puestos como causa de discapacidad. Los tratamientos preventivos habituales hasta ahora derivan de otras indicaciones y por serendipia se utilizan en prevención de migraña: betabloqueantes, drogas antiepilépticas, antidepresivos tricíclicos, bloquean tes de canales de calcio, toxina botulínica. Todas ellas han mostrado eficacia similar al 50% en reducir el número de episodios migrañosos pese a efectos secundarios indeseados. Durante los últimos años, se ha evaluado la eficacia y seguridad de los anticuerpos monoclonales (AM) que actúan sobre la vía del péptido relacionado con el gen de la calcitonina (CGRP) en migraña. Dicho péptido es relevante en la activación del dolor en territorio meníngeoy es mediado por terminales nerviosas trigeminales una vez activado el proceso migrañoso. Su dosaje en crisis migrañosas ha sido elevado en diversos estudios y su neutralización/bloqueo, redunda en alivio del dolor. Los anticuerpos monoclonales erenumab, galcanezumab, fremanezumab, eptinezumab aprobados en el mercado EE.UU./Europa desde 2018 y tras varios trabajos de Fase III y abiertos de extensión, mostraron clara seguridad yeficacia y están presentes en nuestro medio desde mediados de 2019. Desarrollamos la racionalidad e indicaciones de uso de los mismos.

Abstract Migraine is a very prevalent disorder that is estimated to affect about 10-15% of adult subjects. Ac cording to the World Health Organization migraine is one of the first causes of disability. Traditional preventive treatments discovered by serendipity include Beta blockers, antinconvulsants drugs, calcium channel blockers, tricyclic antidepressants and onabotulinum A and offer about 50% efficacy after controlled placebo trials and real life use. Because of lack of adherence and adverse events, there is a loss of beneficial sustain on these treat ments. Recently, the efficacy and safety of monoclonal antibodies (MA) that act on the peptide pathway related to the calcitonin gene (CGRP) has been evaluated in migraine, being the first specific tailored treatment on one of the multiple targets on migraine. This family of drugs: erenumab, galcanezumab, fremanezumab, eptinezumab, finished Fase III, extensions trials and many of them are in the market approved since 2018.Since 2019 are available in Argentina. We will describe the rationale for the prescription of this family of new drugs for migraine.

Peripheral Blood Inflammation Indicators as Predictive Indicators in Immunotherapy of Advanced Non-small Cell Lung Cancer / 中国肺癌杂志

BACKGROUND@#Lung cancer is the leading cause of cancer-related death, of which non-small cell lung cancer (NSCLC) is the most common type. Immune checkpoint inhibitors (ICIs) have now become one of the main treatments for advanced NSCLC. This paper retrospectively investigated the effect of peripheral blood inflammatory indexes on the efficacy of immunotherapy and survival of patients with advanced non-small cell lung cancer, in order to find strategies to guide immunotherapy in NSCLC.@*METHODS@#Patients with advanced non-small cell lung cancer who were hospitalized in The Affiliated Cancer Hospital of Nanjing Medical University from October 2018 to August 2019 were selected to receive anti-PD-1 (pembrolizumab, sintilimab or toripalimab) monotherapy or combination regimens. And were followed up until 10 December 2020, and the efficacy was evaluated according to RECIST1.1 criteria. Progression-free survival (PFS) and overall survival (OS) were followed up for survival analysis. A clinical prediction model was constructed to analyze the predictive value of neutrophil-to-lymphocyte ratio (NLR) based on NLR data at three different time points: before treatment, 6 weeks after treatment and 12 weeks after treatment (0w, 6w and 12w), and the accuracy of the model was verified.@*RESULTS@#173 patients were finally included, all of whom received the above treatment regimen, were followed up for a median of 19.7 months. The objective response rate (ORR) was 27.7% (48/173), the disease control rate (DCR) was 89.6% (155/173), the median PFS was 8.3 months (7.491-9.109) and the median OS was 15.5 months (14.087-16.913). The chi-square test and logistic multi-factor analysis showed that NLR6w was associated with ORR and NLR12w was associated with ORR and DCR. Further Cox regression analysis showed that NLR6w and NLR12w affected PFS and NLR0w, NLR6w and NLR12w were associated with OS.@*CONCLUSIONS@#In patients with advanced non-small cell lung cancer, NLR values at different time points are valid predictors of response to immunotherapy, and NLR <3 is often associated with a good prognosis.

Antibody-drug conjugates in HER2-positive breast cancer / 中华医学杂志(英文版)

Antibody-drug conjugates (ADCs) combine the high specificity of monoclonal antibodies with the high anti-tumor activity of small molecular cytotoxic payloads. The anti-tumor activity of ADCs is mainly achieved by the direct blocking of the receptor by monoclonal antibodies, direct action and bystander effect of cytotoxic drugs, and antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. ADCs have been used in adjuvant therapy and rescue treatment of human epidermal receptor 2 (HER2)-positive breast cancer, greatly improving the prognosis of breast cancer patients. Several ongoing clinical trials of ADC for breast cancer and other solid tumors proved the potential of ADCs will provide more promising treatment options for patients with malignant tumors. This review introduces the mechanism and latest clinical progress of ADC drugs approved for HER2-positive breast cancer to guide clinical practice and conduct research.

Atezolizumab-induced encephalitis in a patient with metastatic breast cancer: a case report and review of neurological adverse events associated with checkpoint inhibitors

Immune-mediated encephalitis as an adverse event due to checkpoint inhibitors is very rare. We describe herein the case of a 38-year-old woman with metastatic triple-negative breast cancer who developed seizures and somnolence twelve days after receiving the first dose of Atezolizumab. Work up ruled out all infectious etiologies, and the patient was eventually diagnosed with immune-mediated meningoencephalitis. Symptoms recovered with a high-dose of steroids, and she was found to have an excellent response on follow-up imaging, which raised the question of whether a relationship exists between the occurrence, and severity of the adverse event and the response to treatment. Only a few other cases of atezolizumab-related encephalitis have been published. Early recognition and treatment are crucial; the reason why we are describing this case along with a review of the literature and a review on all the neurological immune-related adverse events due to the different checkpoint inhibitors.

Obtención de una versión IgG1 de ratón del rituximab para detectar la molécula CD20 humana / Obtaining a mouse IgG1 version of rituximab to detect the human CD20 molecule

Introducción: El rituximab, anticuerpo quimérico que reconoce la molécula CD20 humana, se ha utilizado en el tratamiento de diversos trastornos linfoproliferativos de células B. Para la selección de los potenciales beneficiarios del tratamiento con rituximab se han desarrollado técnicas que, mediante el uso de anticuerpos monoclonales, detectan la presencia del CD20 en los linfocitos de estos pacientes. Objetivo: Obtener y caracterizar un anticuerpo recombinante IgG1 de ratón específico para la molécula CD20 humana, que contenga las regiones variables del anticuerpo rituximab. Métodos: Para la expresión estable del anticuerpo recombinante se empleó la transducción lentiviral de células de embrión de riñón humano (HEK293). La caracterización inmunoquímica del anticuerpo se realizó por la técnica de Western Blot y su capacidad de reconocimiento de la molécula CD20 humana se evaluó por citometría de flujo e inmunohistoquímica. Resultados: Se obtuvo el anticuerpo 1F5 que reconoce, por citometría de flujo, la molécula CD20 en líneas celulares humanas de origen linfoide, así como en células de sangre periférica de humanos sanos y pacientes con trstornos linfoproliferativos de células B. Sin embargo, la técnica de inmunohistoquímica solo permitió detectar con este anticuerpo la molécula CD20 en tejidos frescos, no así en los embebidos en parafina. Conclusiones: Este trabajo sugiere las potencialidades del uso del anticuerpo 1F5 para las mediciones de la expresión de CD20 por citometría de flujo en pacientes con leucemias B o linfomas B avanzados en fase de leucemización. Esto complementaría los estudios para la selección apropiada de pacientes para el tratamiento con el rituximab(AU)

Introduction: Rituximab, chimeric antibody specific for human CD20 molecule, has been widely used in the treatment of several B-cell linfoproliferative disorders. For the selection of patients with the greatest potential to benefit from the therapy with rituximab, a number of techniques using monoclonal antibodies have been developed to detect the CD20 molecule. Objective: To obtain and to characterize a mouse IgG1 recombinant antibody, specific for human CD20, that contains the variable regions of rituximab. Methods: The lentiviral transduction of human embryonic kidney cells (HEK293) was used for the stable expression of the recombinant antibody. The immunochemical characterization of the antibody was performed by Western Blot and the recognition of CD20 was evaluated by immunohistochemistry and flow cytometry. Results: We generated the antibody 1F5, able to recognize by flow cytometry the CD20 molecule expressed on lymphoid human cell lines, as well as peripheral blood mononuclear cells from healthy donors and patients with B-cell lymphoproliferative disorders. However, 1F5 antibody detected the CD20 molecule on fresh tissues, but not on formalin-fixed paraffin embedded tissues,by immunohistochemistry. Conclusions: This work suggests the potential use of 1F5 antibody for the measurement of CD20 expression by flow cytometry in patients with B-cell leukemias or B-cell lymphomas in phase of leukemization. This could complement the studies to ensure the appropriate selection of patients for the treatment with rituximab(AU)

Infectious complications as a predictor of mortality in patients with Non-Hodgkin lymphoma receiving rituximab- containing chemotherapy

Abstract Background Rituximab is a monoclonal antibody that increases the disease-free and overall survival of patients with non-Hodgkin lymphoma (NHL) CD20+. The objective of this study is to describe the prevalence and spectrum of infections in patients with NHL receiving rituximab-containing chemotherapy and the impact on survival. Materials and Methods From January 2011 to December 2012, all patients diagnosed with NHL who received at least one dose of rituximab were included. Results During the study period, 265 patients received rituximab; 108 (40.8%) males; the mean age was 60 ± 15 years. There were 177 infections in 85 patients, being the most common febrile neutropenia (n = 38; 21.5%) and mucosal barrier injury-related infections (n = 28; 15.8%). In 88 events (49%), there was a microbiologic diagnosis, being bacterial infection the most frequent (39.6%), but tuberculosis (TB) was developed in 4 cases (1.5%; incidence rate 721/100,000 person-year). During follow-up, 71 patients died (27%); in 35 cases, it was related to infection. There were no differences in follow-up between those who died due to infection versus those who died from another cause (p = 0.188). Multivariate analysis for mortality showed that age >60 years, failure to achieve a complete response, and development of an infectious complication increased the risk of death. Conclusions It is important to perform a screening test for TB in all patients who will receive rituximab and maintain a constant monitoring to detect an infectious process and begin treatment as soon as possible.

Uso de rituximabe no tratamento de linfoma linfoplasmocítico durante terapia de substituição renal contínua / Rituximab use for lymphoplasmacytic lymphoma during continuous renal replacement therapy

RESUMO A segurança e a eficácia do rituximabe em pacientes com comprometimento renal não foram estabelecidas, e o mesmo ocorre com os efeitos da hemodiálise nos níveis séricos de rituximabe. Atualmente, apenas alguns relatos de caso avaliaram o nível sérico de rituximabe antes e após a diálise. Não foram até aqui publicados dados relativos ao uso de rituximabe em pacientes sob terapia de substituição renal contínua. Os autores apresentam um caso referente a uma mulher com 59 anos de idade atendida com quadro de tetraparesia paraneoplásica. Ela foi admitida no serviço de medicina intensiva devido a hemorragia alveolar com insuficiência respiratória e lesão renal aguda, que necessitou da utilização de terapia de substituição renal contínua. Após os procedimentos diagnósticos, estabeleceu-se o diagnóstico de linfoma linfoplasmocítico. Deu-se início ao tratamento com rituximabe e ciclofosfamida. Os níveis de rituximabe foram determinados no soro e no dialisato. Não se encontrou qualquer nível de rituximabe no dialisato. A paciente faleceu após 2 meses no serviço de medicina intensiva por pneumonia nosocomial causada por Pseudomonas aeruginosa resistente a múltiplos fármacos.

ABSTRACT Rituximab safety and efficacy in patients with renal impairment have not been established, nor have the effects of hemodialysis on serum rituximab level. There are only a few published case reports assessing serum rituximab level pre- and postdialysis. No data have been published regarding the usage of rituximab in patients with continuous renal replacement therapy. The authors present a case of a 59-year-old female patient who presented with paraneoplastic tetraparesis. She was admitted to the intensive care unit due to alveolar hemorrhage with respiratory failure and acute kidney injury requiring continuous renal replacement therapy. After a diagnostic workup, the diagnosis of lymphoplasmacytic lymphoma was established. Therapy with rituximab and cyclophosphamide was started. Rituximab levels were determined in serum and dialysate. No rituximab was found in the dialysate. The patient died after 2 months in the intensive care unit from nosocomial pneumonia due to multidrug-resistant Pseudomonas aeruginosa.

Macroglobulinemia de Waldenström: experiencia de 15 años en el Hospital del Salvador, Santiago, Chile / Waldenström macroglobulinemia: experience in 31 patients

Background: Waldenström macroglobulinemia (WM) is an uncommon indolent B-cell lymphoma, due to the proliferation of lymphoplasmacytic cells, and secretion of a monoclonal IgM protein. Aim: To evaluate the clinical characteristics, management and results of treatment of patients with WM at a public hospital in Chile. Patients and Methods: Review of medical records of 31 patients aged 43 to 85 years (16 males) with WM diagnosed between 2002 and 2017. Clinical features and survival were recorded. Results: All patients had bone marrow compromise, and 31%, extranodal involvement. According to the International Prognostic Score System for WM (IPSSWM) 16, 58 and 26% were at low, intermediate and high risk, respectively. Twenty-five patients (81%) were treated, 32% with plasmapheresis and 36% with rituximab. Four cases (16%) achieved complete remission. Median follow up was 35 months (range 6-159). Estimated overall survival (OS) at 5 and 10 years was 74% and 53%, respectively. According to IPSSWM, the estimated five-year OS was 80, 92 and 39%, for low, intermediate and high-risk patients, respectively. Conclusions: OS was similar to that reported abroad, except for low risk patients, probably due to the low number of cases and short follow up. An improved survival should be expected with the routine use of immunochemotherapy.

Progress of Bevacizumab in Malignant Pleural Effusion Caused by Non-small Cell Lung Cancer / 中国肺癌杂志

Lung cancer is the most commonly diagnosed cancer worldwide. Malignant pleural effusion (MPE) caused by advanced lung cancer seriously affect the patients' quality of life and prognosis. The management of MPE includes thoracentesis, pleurodesis, indwelling pleural catheters and drug perfusion in pleural cavity. Vascular endothelial growth factor (VEGF) and its receptor are a group of important ligands and receptors that affect angiogenesis. They are the main factors controlling angiogenesis, and they play an important role in the formation of MPE. Bevacizumab is a recombinant humanized VEGF monoclonal antibody, competitively binding to endogenous VEGF receptor. Bevacizumab can inhibit new blood vessel formation, reduce vascular permeability, prevent pleural effusion accumulation and slow the growth of cancers. This review aims to discuss the progress of bevacizumab in the treatment of MPE caused by non-small cell lung cancer (NSCLC), and explore the clinical application, efficacy, safety and future direction of bevacizumab.
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