Follicular Lymphoma in Chile in the Adult Public Cancer Program: The Impact of Chemoimmunotherapy.

BACKGROUND: Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma (NHL) in the United States and Europe. However, data on FL from Latin America are scant. AIMS: This study aims at better understand the clinical features, treatment patterns and outcomes of patients with FL in Chile. Of special interest was to evaluate POD24 as an adverse marker. METHODS AND RESULTS: We collected retrospective data from 722 patients 15 years or older diagnosed with FL and treated in 17 cancer centers in Chile between 2000 and 2019. Time to first treatment (TTFT), progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Cox proportional-hazard regression models were fitted to investigate prognostic factor. The median age at diagnosis was 62 with a female predominance (63%); 73% of patients had advance stage disease and 68% had bone marrow involvement; 63% had intermediate or high FLIPI scores. The 1-year TTFT rate was 96%, and 30% of patients received chemoimmunotherapy. Adding rituximab to chemotherapy was associated with a higher complete response (69% vs. 60%; p < 0.001) and superior median OS (16 vs. 8 years; p < 0.001). Patients who experience POD24 had an inferior median OS (2.4 vs. 15 years). CONCLUSION: Our study shows a female predominance in patients with FL in Chile and confirms superior response and survival outcomes with adding rituximab to chemotherapy. Our study also confirms a poor OS in patients who experience POD24.

2023 Brazilian Society of Rheumatology guidelines for the treatment of systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc) is a rare chronic autoimmune disease with heterogeneous manifestations. In the last decade, several clinical trials have been conducted to evaluate new treatment options for SSc. The purpose of this work is to update the recommendations of the Brazilian Society of Rheumatology in light of the new evidence available for the pharmacological management of SSc. METHODS: A systematic review including randomized clinical trials (RCTs) for predefined questions that were elaborated according to the Patient/Population, Intervention, Comparison, and Outcomes (PICO) strategy was conducted. The rating of the available evidence was performed according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. To become a recommendation, at least 75% agreement of the voting panel was needed. RESULTS: Six recommendations were elaborated regarding the pharmacological treatment of Raynaud's phenomenon, the treatment (healing) and prevention of digital ulcers, skin involvement, interstitial lung disease (ILD) and gastrointestinal involvement in SSc patients based on results available from RCTs. New drugs, such as rituximab, were included as therapeutic options for skin involvement, and rituximab, tocilizumab and nintedanib were included as therapeutic options for ILD. Recommendations for the pharmacological treatment of scleroderma renal crisis and musculoskeletal involvement were elaborated based on the expert opinion of the voting panel, as no placebo-controlled RCTs were found. CONCLUSION: These guidelines updated and incorporated new treatment options for the management of SSc based on evidence from the literature and expert opinion regarding SSc, providing support for decision-making in clinical practice.

Rituximab as Treatment for Lupus Nephritis: Data From the Peruvian ALMENARA Lupus Cohort.

OBJECTIVE: The aim of this study was to evaluate the response to rituximab (RTX) as treatment for lupus nephritis (LN) in a Latin American Lupus cohort. METHODS: The medical records from LN patients from a single-center cohort spanning between January 2012 and December 2020 were reviewed. Demographic factors (age at diagnosis and baseline, gender), disease duration, previous and concomitant treatments, serum creatinine, and 24-hour proteinuria (24-HP) levels at baseline, and 6th and 12th months were obtained. Complete response (CR) or responder status was defined according to the LUNAR, AURORA-1, and BLISS-LN trials. RESULTS: Thirty-six patients received RTX as induction treatment; 32 (88.9%) were women. Their age at baseline and disease duration were 32.6 (11.7) and 7.6 (6.5) years, respectively. The time between renal biopsy and RTX use was 2.64 (4.41) years. At baseline, serum creatinine and 24-HP levels were 1.5 (1.5) mg/dL and 3.4 (2.8) g, respectively. At months 6 and 12, serum creatinine levels were 1.6 (1.6) and 1.6 (1.5) mg/dL, and 24-HP were 2.2 (2.2) and 1.6 (1.5) g, respectively. According to LUNAR and AURORA-1 criteria, CR at 6th and 12th months were 6/34 (17.6%) and 8/30 (26.7%) and 6/34 (17.6%) and 7/31 (22.6%) patients, respectively. According to BLISS-LN criteria, responders at 6th and 12th months were 9/34 (26.5%) and 10/31 (32.3%) patients, respectively. CONCLUSIONS: CR and responder status were reached in less than one third of LN patients treated with RTX, regardless of the criteria used to define them. However, serum creatinine levels did not increase, and there was a decrease in proteinuria levels during the follow-up.

Traditional first-line treatment failure rates in neuromyelitis optica spectrum disorder patients included in the Argentinean registry (RelevarEM).

BACKGROUND: Immunosuppressive therapies as azathioprine (AZA), mycophenolate mofetil (MMF) and rituximab (RTX) are widely prescribed as first-line treatment to prevent relapses in NMOSD. However, the rate of response to these traditional therapies is unknown in Argentina. We aimed to describe and compare treatment failure rates in NMOSD patients included in the Argentinean MS and NMOSD registry (RelevarEM, NCT03375177). METHODS: A retrospective cohort study was conducted in NMOSD patients included in RelevarEM (a nationwide, longitudinal, observational, non-mandatory registry of MS and NMOSD in Argentina). NMOSD patients were defined based on validate diagnostic criteria. Only NMOSD patients who received AZA or MMF for at least 6 months or RTX for at least 1 month were included. Patients who were receiving AZA, MMF, or RTX and then switched to another 1 of these 3 therapies were included if the above-mentioned criteria for each drug were fulfilled. Data on patient demographics, clinical, neuroradiological findings, and treatments administered were collected. Treatment failure was defined as any new attack/relapse that occurred despite immunosuppressive treatment. RESULTS: We included 139 NMOSD patients who were receiving AZA (n = 105), MMF (n = 5) or RTX (n = 29) with a mean follow-up time of 41.3 ± 11.4 months and median of EDSS at treatment initiation of 3. We observed a reduction in the annualized relapse rate from pre-treatment to post-treatment of 51.1 %, 48.4 %, and 79.1 % respectively with a Hazard Risk relative to RTX (95 % CI) of 1.67 (1.34-3.54, p = 0.01) for AZA and 2.01 (1.86-4.43, p = 0.008) for MMF. AZA, MMF and RTX failure was observed in 45/105 (42.8 %), 2/5 (40 %) and 3/29 (10.3 %) patients, respectively. CONCLUSIONS: Treatment failure rates were higher for AZA and MMF than RTX in Argentinean NMOSD patients in a real-world setting. High-efficacy treatment increases the opportunity to prevent attacks of NMOSD.

Updates in diagnosis and treatment of pediatric antiphospholipid syndrome.

PURPOSE OF REVIEW: This review offers an overview of the most important recent articles on pediatric APS. RECENT FINDINGS: Non-thrombotic extra criteria manifestations were prevalent in pediatric APS. Pregnancy morbidity has been described as the first manifestation of APS at youth age, impairing gestational outcomes. The 2023 APS criteria were developed for adult APS patients, and there is still a lack of pediatric-specific APS criteria. Catastrophic APS was more commonly reported as the initial manifestation of pediatric APS than in adults. Regarding treatment, direct oral anticoagulants have been recently approval for pediatric patients with venous thrombosis. New approaches have been proposed for severe cases, for arterial thrombosis, and rituximab for refractory cases. Recurrences typically occurred early and were associated with older age at diagnosis. Current studies highlighted the multifaceted nature of pediatric APS. Further large prospective multicenter studies evaluating new medications capable of reducing recurrence risk and improving prognosis in this population will be required.

II Brazilian Society of Rheumatology consensus for lupus nephritis diagnosis and treatment.

OBJECTIVE: To develop the second evidence-based Brazilian Society of Rheumatology consensus for diagnosis and treatment of lupus nephritis (LN). METHODS: Two methodologists and 20 rheumatologists from Lupus Comittee of Brazilian Society of Rheumatology participate in the development of this guideline. Fourteen PICO questions were defined and a systematic review was performed. Eligible randomized controlled trials were analyzed regarding complete renal remission, partial renal remission, serum creatinine, proteinuria, serum creatinine doubling, progression to end-stage renal disease, renal relapse, and severe adverse events (infections and mortality). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to develop these recommendations. Recommendations required ≥82% of agreement among the voting members and were classified as strongly in favor, weakly in favor, conditional, weakly against or strongly against a particular intervention. Other aspects of LN management (diagnosis, general principles of treatment, treatment of comorbidities and refractory cases) were evaluated through literature review and expert opinion. RESULTS: All SLE patients should undergo creatinine and urinalysis tests to assess renal involvement. Kidney biopsy is considered the gold standard for diagnosing LN but, if it is not available or there is a contraindication to the procedure, therapeutic decisions should be based on clinical and laboratory parameters. Fourteen recommendations were developed. Target Renal response (TRR) was defined as improvement or maintenance of renal function (±10% at baseline of treatment) combined with a decrease in 24-h proteinuria or 24-h UPCR of 25% at 3 months, a decrease of 50% at 6 months, and proteinuria < 0.8 g/24 h at 12 months. Hydroxychloroquine should be prescribed to all SLE patients, except in cases of contraindication. Glucocorticoids should be used at the lowest dose and for the minimal necessary period. In class III or IV (±V), mycophenolate (MMF), cyclophosphamide, MMF plus tacrolimus (TAC), MMF plus belimumab or TAC can be used as induction therapy. For maintenance therapy, MMF or azathioprine (AZA) are the first choice and TAC or cyclosporin or leflunomide can be used in patients who cannot use MMF or AZA. Rituximab can be prescribed in cases of refractory disease. In cases of failure in achieving TRR, it is important to assess adherence, immunosuppressant dosage, adjuvant therapy, comorbidities, and consider biopsy/rebiopsy. CONCLUSION: This consensus provides evidence-based data to guide LN diagnosis and treatment, supporting the development of public and supplementary health policies in Brazil.

Lenalidomida em combinação com rituximabe para pacientes com linfoma folicular previamente tratados / Lenalidomide in combination with rituximab for patients with previously treated follicular lymphoma

INTRODUÇÃO: O LF é um tipo de linfoma não Hodgkin (LNH) que se desenvolve pela produção anormal de linfócitos B. No Brasil, sem considerar os tumores de pele não melanoma, o LNH em homens é o oitavo mais frequente. Para as mulheres, LNH é o nono mais frequente. A resposta do LF ao tratamento de primeira linha é geralmente satisfatória e duradoura; no entanto, em alguns pacientes, o câncer recidiva ou progride após um período variável de inatividade da doença. Transplante alogênico de células- tronco hematopoiéticas (TCTH) tem potencial curativo no LF; no entanto, raramente é empregado, pois muitos pacientes são inelegíveis para transplante devido à idade avançada ou indisponibilidade do doador. A quimioimunoterapia com um anticorpo monoclonal anti-CD20 (rituximabe) associado à quimioterapia (ciclofosfamida, doxorrubicina, vincristina, prednisona (CHOP) ou bendamustina) tornou-se uma recomendação mundial para os pacientes com LF que progrediram ao tratamento de primeira linha ou recidivaram. No entanto, a quimioimunoterapia pode n

Rituximabe em monoterapia para pacientes com linfoma folicular assintomático, independentemente do estádio inicial / Rituximab monotherapy for patients with asymptomatic follicular lymphoma, regardless of initial stage

INTRODUÇÃO: O linfoma folicular (LF) é um tipo de linfoma não Hodgkin (NHL) que se desenvolve quando o corpo produz linfócitos B anormais. No Brasil, sem considerar os tumores de pele não melanoma, o linfoma não Hodgkin em homens é o oitavo mais frequente (2,9%). Para as mulheres, linfoma não Hodgkin é o nono mais frequente (2,4%). Dados de estudos retrospectivos em pacientes assintomáticos com linfoma de baixo grau em estágio avançado não mostraram redução na sobrevida global quando o tratamento sistêmico foi adiado até o desenvolvimento de sintomas ou falência de órgãos, que geralmente ocorreu cerca de 30 meses após o diagnóstico. Esses achados foram subsequentemente confirmados através de estudos randomizados e os resultados observados apoiam a estratégia amplamente praticada de 'espera vigilante'. O rituximabe é um anticorpo monoclonal quimérico dirigido contra o CD20. Quando usado isoladamente em pacientes não tratados previamente com LF de baixa carga tumoral, 80% dos pacientes apresentaram uma resposta (52% resposta completa ou resposta completa não confirmada e 28% resposta parcial) e 48% dos pacientes avaliados alcançaram uma remissão molecular completa após apenas quatro infusões semanais. O rituximabe apresenta um perfil favorável de efeitos colaterais, o que permite considerar seu uso em pacientes assintomáticos. Assim, o objetivo do presente relatório é analisar as evidências científicas sobre eficácia, segurança, bem como evidências econômicas referentes a uma possível incorporação do rituximabe em monoterapia para o tratamento de pacientes com LF assintomático, independentemente do estádio inicial. PERGUNTA: Em pacientes com linfoma folicular assintomático, independentemente do estádio inicial (sem critérios de tratamento imediato), o rituximabe em monoterapia é eficaz, seguro, custo-efetivo e viável economicamente quando comparado com a espera vigilante? EVIDÊNCIAS CLÍNICAS: Foi incluído um ensaio clínico randomizado (ECR) no qual foram comparadas três condutas, a saber, tratamento de indução com rituximabe (RTX); manutenção com RTX e espera vigilante. Três anos após o início da inscrição, o recrutamento para o grupo de indução com rituximabe foi encerrado porque outros estudos mostraram um benefício da manutenção do rituximabe em comparação com a espera vigilante após a indução com rituximabe com ou sem quimioterapia. O desenho do estudo foi revisado, mantendo-se dois dos três braços (espera vigilante versus manutenção com rituximabe). AVALIAÇÃO ECONÔMICA (AE): Foi realizada uma análise de sobrevida particionada com horizonte temporal de 40 anos (lifetime), considerando os estados de saúde pré e pósprogressão e morte, construída a partir dos dados de SG e SLP do ECR identificado. A indução e manutenção com rituximabe se apresentaram como intervenções dominantes, reduzindo os custos relacionados com a progressão da doença e com benefício incremental em termos de anos de vida ajustados pela qualidade (AVAQ) (0,34 e 0,71 AVAQ, respectivamente) quando comparado à espera vigilante. ANÁLISE DE IMPACTO ORÇAMENTÁRIO (AIO): A população elegível foi estimada pelo método de demanda epidemiológica. Os custos considerados foram os relacionados ao tratamento medicamentoso e aos cuidados com a doença nos estágios pré- e pósprogressão. A incorporação de rituximabe pode aumentar o orçamento ao longo de cinco anos em R$ 110.517 num cenário onde apenas a terapia de indução estaria disponível e de R$ 883.461 num cenário onde tanto a terapia de indução quanto terapia de manutenção estariam disponíveis. PERSPECTIVA DO PACIENTE: Foi aberta a Chamada Pública n. 3 de 2024 no período de 29 de janeiro a 7 de fevereiro do mesmo ano e quatro pessoas se inscreveram. A definição dos representantes titular e suplente foi realizada por sorteio em plataforma digital, com transmissão em tempo real e acessível a todos os inscritos. No relato, a representante de associação de pacientes apresentou dois relatos de pacientes: a primeira realizou quimioterapia com R-CHOP e teve prescrição de uso do rituximabe para manutenção do tratamento, mas ainda está aguardando o acesso por via judicial; a segunda teve indicação de uso do medicamento como primeira opção de tratamento e, após utilizá-lo por quatro semanas, a doença entrou em remissão. RECOMENDAÇÕES DE AGÊNCIAS INTERNACIONAIS DE ATS: Foi encontrada uma avaliação do rituximabe em monoterapia para o tratamento de indivíduos com LF assintomático, independentemente do estádio inicial no NICE (Inglaterra). Nenhuma avaliação da tecnologia foi encontrada no SMC (Escócia), CADTH (Canadá) e PBAC (Austrália). O NICE (Reino Unido) recomenda a terapia de indução com rituximabe para pessoas com LF em estágio avançado (estágios III e IV) que são assintomáticos. MONITORAMENTO DO HORIZONTE TECNOLÓGICO: Uma tecnologia foi detectada para compor o tratamento do linfoma folicular, independentemente do estádio inicial, sem sintomas e sem critérios de tratamento imediato. O medicamento odronextamab é um anticorpo monoclonal anti-CD20, sem registro sanitário ou avaliação de ATS. Não foram identificados resultados para os ensaios clínicos em andamento. CONSIDERAÇÕES FINAIS: A partir da avaliação dos resultados concluiu-se que em pacientes com LF assintomático em estágio avançado de baixa carga tumoral, a SLP, após o uso do rituximabe de manutenção, foi significativamente maior do que a observada nos grupos que receberam a conduta da espera vigilante ou tratamento de indução com rituximabe sem manutenção. As avaliações econômicas demonstraram que a indução com rituximabe foi dominante e a sua incorporação aumentaria o orçamento ao longo de cinco anos em R$ 110.517 (apenas terapia de indução) até R$ 883.461 (terapia de indução e terapia de manutenção). Cabe destacar que, nas avaliações econômicas, foram considerados os resultados do ensaio clínico para os desfechos de SG e SLP; e que há controversas na literatura e na prática clínica sobre a introdução da terapia sistêmica para pacientes com LF assintomáticos. RECOMENDAÇÃO PRELIMINAR DA CONITEC: Os membros do Comitê de Medicamentos presentes na 127ª Reunião da Conitec, realizada no dia 07 de março de 2024, deliberaram que a matéria fosse disponibilizada em consulta pública com recomendação preliminar desfavorável à incorporação ao SUS do rituximabe em monoterapia para pacientes com LF assintomáticos, independentemente do estádio inicial (sem critérios de tratamento imediato). Apesar das evidências apresentadas e do potencial benefício em termos de sobrevida livre de progressão, discutiu-se que a recomendação de tratamento para pacientes assintomáticos ainda é controversa na prática clínica e entre as diretrizes internacionais, e que se deve considerar, sobretudo, os riscos e benefícios do tratamento sistêmico precoce. Além disso, as evidências demonstraram não haver benefícios na sobrevida global e com resultados limitados na melhora da qualidade de vida, ao passo que a sobrevida livre de progressão pode não ser um desfecho prioritário para decisão de tratamento no contexto do linfoma folicular, tendo em vista a sua natureza semiobjetiva. CONSULTA PÚBLICA: A Consulta Pública nº 15 foi realizada entre os dias 09 e 29 de abril de 2024, recebendo o total de 107 contribuições. Todas foram submetidas à análise de conteúdo temática. Das 107 contribuições recebidas, 106 foram desfavoráveis à recomendação inicial da Conitec de não incorporação do medicamento no SUS e uma foi a favor da recomendação. Os argumentos favoráveis à incorporação do rituximabe em monoterapia para pacientes com linfoma folicular assintomático contemplavam os efeitos positivos, tais como a remissão da doença e a qualidade de vida. Os participantes relataram, como principal ponto negativo, a dificuldade de acesso ao medicamento, o alto custo e alguns eventos adversos, em sua maioria considerados esperados e leves. Foram identificadas 98 (91,6%) contribuições vazias para as evidências clínicas e 98 (91,6%) para estudos econômicos. RECOMENDAÇÃO FINAL DA CONITEC: Os membros do Comitê de Medicamentos da Comissão Nacional de Incorporação de Tecnologias no Sistema Único de Saúde ­ Conitec, presentes na 130ª reunião ordinária, no dia 6 de junho de 2024, deliberaram, por unanimidade, recomendar a não incorporação do rituximabe em monoterapia para pacientes com LF assintomático, independente do estádio inicial. Considerou-se que não houve adição de informações relevantes para modificar o entendimento inicial de que as evidências científicas de benefício do medicamento são limitadas e que não há consenso entre especialistas sobre o tratamento do linfoma folicular na fase assintomática. Foi assinado o Registro de Deliberação nº 903/2024. DECISÃO: não incorporar, no âmbito do Sistema Único de Saúde - SUS, o rituximabe em monoterapia para pacientes com linfoma folicular assintomático, independentemente do estádio inicial, publicada no Diário Oficial da União nº 142, seção 1, página 73, em 25 de julho de 2024.

Description of therapeutic strategies in severe systemic lupus erythematosus-associated immune thrombocytopenia: a retrospective cohort study of response and relapse.

OBJECTIVES: To describe the response and relapse of severe thrombocytopenia in patients with systemic lupus erythematosus (SLE) with different treatments. METHOD: We performed a retrospective cohort study, which included SLE patients who were hospitalized for thrombocytopenia of less than 30,000/µL platelets, from January 2012 to December 2021. Demographic and clinical information was obtained from clinical records. Kaplan-Meier and logrank test were performed. RESULTS: Forty-seven patients, mostly women (83%) with a median age of 31 years, were included in the study. Eight patients (17%) relapsed within a median period of 35.7 weeks. Initial acute treatment with prednisone at 1 mg/kg/day was as effective as glucocorticoid pulses. However, induction treatment with cyclophosphamide (CYC) had the lowest remission rate (43%, p = 0.034). There was no significant difference in relapse-free survival (RFS) among the acute glucocorticoid treatments. CYC induction was associated with lower RFS compared to rituximab (RTX) (CYC 43.6 weeks vs. RTX 51.8 weeks, p = 0.040) or azathioprine (AZA) (CYC 43.6 weeks vs. AZA 51.2 weeks, p = 0.024). Administration of antimalarials was associated with longer RFS (51.6 weeks vs. 45.0 weeks, p = 0.021). Factors such as antiphospholipid syndrome, IgG anti-ß2 glycoprotein I positivity, renal and additional hematologic SLE activity during follow-up significantly reduced RFS. CONCLUSIONS: Despite similar response of acute glucocorticoid regimens, induction therapy with AZA or RTX resulted in a longer RFS compared to CYC. Adding an antimalarial also improved RFS. Our study provides evidence that may help develop better treatment strategies for severe thrombocytopenia in SLE patients. Key Points • Induction therapy with azathioprine or rituximab provided longer relapse-free survival in SLE thrombocytopenia compared with cyclophosphamide. • Antimalarial administration was associated with longer relapse-free survival in SLE thrombocytopenia. • Antiphospholipid syndrome, IgG anti-ß2 glycoprotein I positivity, as well as renal and additional hematologic SLE activity during follow-up, decreased relapse-free survival.

Navigating the diagnostic maze: A case presentation of C1q vasculitis mimicking hypocomplementemic urticarial vasculitis in a patient with systemic lupus erythematosus.

In rare instances, patients with SLE may exhibit atypical clinical manifestations, such as Hypocomplementemic Urticarial Vasculitis, which can pose diagnostic challenges. Here, we present a case report of a 28-year-old female with a history of SLE with lupus nephritis clase IV who developed HUV-like symptoms, ultimately leading to a diagnosis of C1q Vasculitis. This case underscores the importance of considering C1q Vasculitis in SLE patients presenting with HUV-like features and highlights Rituximab as a promising therapeutic option for managing this rare condition.

The effect of metabolic syndrome on prognosis of diffuse large B-cell lymphoma.

PURPOSE: Metabolic syndrome (MetS), characterized by insulin resistance, is closely associated with the prognosis of various cancer types, but has not been reported in diffuse large B-cell lymphoma (DLBCL). The aim of this study is to examine how other clinicopathological variables and the MetS influence the prognosis of DLBCL. METHODS: Clinical and pathological data were collected from 319 patients with DLBCL who were admitted to our hospital between January 2012 and December 2020. The data accessible with SPSS 27.0 enables the utilization of various statistical methods for clinical data analysis, including independent sample t test and univariate and multivariate COX regression. RESULTS: The presence of MetS was linked to both overall survival (OS) and progression-free survival (PFS), in addition to other clinicopathological characteristics as age, IPI score, rituximab usage, and Ki-67 expression level. This link with OS and PFS indicated a poor prognosis, as shown by survival analysis. Subsequent univariate analysis identified IPI score, Ki-67 expression level, tumor staging, rituximab usage, lactate dehydrogenase expression level, and the presence or absence of MetS as factors linked with OS and PFS. Furthermore, multivariate Cox regression analysis confirmed the independent risk factor status of IPI score, Ki-67 expression level, rituximab usage, and the presence of MetS in evaluating the prognosis of patients with DLBCL. CONCLUSION: This study's findings indicate that patients with pre-treatment MetS had a poor prognosis, with relatively shorter OS and PFS compared to those without pre-treatment MetS. Furthermore, the presence of MetS, IPI score, Ki-67 expression level, and rituximab usage were identified as independent risk factors significantly affecting the prognosis of DLBCL.

Real-World Outcomes of Adolescents and Young Adults with Diffuse Large B-Cell Lymphoma: A Multicenter Retrospective Cohort Study.

Purpose: Patients with diffuse large B-cell lymphoma (DLBCL) are typically treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, a standard of care for managing adolescents and young adults (AYAs) with DLBCL is lacking. We examine treatment approaches and outcomes of this population. Methods: We included 90 AYAs (15-39 years) diagnosed with DLBCL between 2008 and 2018 in three tertiary centers in Peru. Overall response rates (ORR) were available for all patients. Overall survival (OS) and progression-free survival (PFS) rates were estimated using the Kaplan-Meier method. Results: The median age at diagnosis was 33 years, 57% were males, 57% had good performance status (Lansky/Karnofsky ≥90), and 61% were diagnosed with early-stage disease (Ann Arbor stages I-II). R-CHOP (n = 69, 77%) was the most frequently used first-line regimen, with an ORR of 91%. With a median follow-up of 83 months, the 5-year OS and PFS among all patients were 79% and 67%, respectively. Among the patients who received R-CHOP, the 5-year OS and PFS were 77% and 66%, respectively. Of the 29 (32%) patients with relapsed/refractory (R/R) disease, 83% received second-line treatment and only 14% underwent consolidation therapy with autologous transplantation. The 3-year OS for R/R DLBCL was 36%. Conclusion: Our data show that AYAs with DLBCL who received conventional therapy had comparable outcomes to those observed in studies conducted among the adult population. However, the prognosis for AYAs with R/R disease was dismal, indicating the unmet need for developing and increasing access to novel treatment modalities in AYAs.

Improved survival for dose-intensive chemotherapy in primary mediastinal B-cell lymphoma: a systematic review and meta-analysis of 4,068 patients.

Primary mediastinal B-cell lymphoma (PMBCL) is a distinct clinicopathologic entity. Currently, there is a paucity of randomized prospective data to inform on optimal front-line chemoimmunotherapy (CIT) and use of consolidative mediastinal radiation (RT). To assess if distinct CIT approaches are associated with disparate survival outcomes, we performed a systematic review and meta-analysis comparing dose-intensive (DI-CIT) versus standard CIT for the front-line treatment of PMBCL. Standard approach (S-CIT) was defined as R-CHOP-21/CHOP-21, with or without RT. DI-CIT were defined as regimens with increased frequency, dose, and/or number of systemic agents. We reviewed data on 4,068 patients (2,517 DI-CIT; 1,551 S-CIT) with a new diagnosis of PMBCL. Overall survival for DI-CIT patients was 88% (95% CI: 85-90) compared to 80% for the S-CIT cohort (95% CI: 74-85). Meta-regression revealed an 8% overall survival (OS) benefit for the DI-CIT group (P<0.01). Survival benefit was maintained when analyzing rituximab only regimens; OS was 91% (95% CI: 89-93) for the rituximab-DI-CIT arm compared to 86% (95% CI: 82-89) for the R-CHOP-21 arm (P=0.03). Importantly, 55% (95% CI: 43-65) of the S-CIT group received RT compared to 22% (95% CI: 15-31) of DI-CIT patients (meta-regression P<0.01). To our knowledge, this is the largest meta-analysis reporting efficacy outcomes for the front-line treatment of PMBCL. DI-CIT demonstrates a survival benefit, with significantly less radiation exposure, curtailing long-term toxicities associated with radiotherapy. As we await results of randomized prospective trials, our study supports the use of dose-intensive chemoimmunotherapy for the treatment of PMBCL.

Diffuse Large B-Cell Lymphoma with Cutaneous Manifestations in a Young Patient Using Clozapine for Schizophrenia: A Case Report.

BACKGROUND Non-Hodgkin lymphoma is the most common hematological malignancy in the world. Diffuse large B-cell lymphoma the most common type and the cutaneous involvement due to this neoplasm is rare. Some risk factors, such as exposure to pesticides, alcohol consumption, and tobacco use, are well established. Over the past 10 years, the association between clozapine, which is the criterion standard treatment for refractory schizophrenia, and hematological malignancies has been described. CASE REPORT We report a case of a 44-year-old woman diagnosed with schizophrenia 31 years previously, who had been taking clozapine since 2009, presenting with diffuse cutaneous nodules and subcutaneous masses accompanied by asthenia, dry cough, and a weight loss of 12 kg. Computed tomography revealed multiple enlarged lymph nodes on both sides of the diaphragm, in addition to multiple large subcutaneous masses located on the right flank and on the right upper lateral chest wall (infra-axillary), homogeneous splenomegaly, and heterogeneous nodular areas of hypoenhancement, poorly delimited, in both kidneys. Diffuse large B-cell lymphoma in an advanced stage (IVBX) was diagnosed by skin biopsy, with extranodal involvement. Chemotherapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone every 21 days) was performed and the decision to maintain clozapine was made. At 1.5 years after the initial diagnosis the patient presented with relapse of the disease and is in follow-up. CONCLUSIONS This case report suggests the potential association between clozapine and an increased risk of lymphoma, with a few case reports in the literature reinforcing this association. Additional studies are required to either confirm or dismiss this association, and new guidelines are needed to define the safety and monitoring of the long-term usage of clozapine.

[Report of two cases of anti-LGI1 autoimmune encephalitis in Mexico]. / Reporte de dos casos de encefalitis autoinmune anti-LGI1 en México.

Background: Anti-LGI1 encephalitis is characterized by a pattern of inflammation that predominantly affects the limbic system It is part of the autoimmune encephalitis that attack neuronal surface antigens. It is characterized by the triad of subacute dementia, faciobrachial dystonic crises, and hyponatremia, presenting an excellent response to immunotherapy. The aim of this article is to describe the clinical evolution and functional outcome at 6 months of two patients with anti-LGI1 encephalitis using clinical cases. Clinical cases: Case 1: 62-year-old man with 8-week symptoms manifested by changes in mood, disorientation, and focal motor seizures. Case 2 A 72-year-old woman with a 5-month evolution of rapidly progressive dementia, hyponatremia and bitemporal hyperintensities on MRI. In both, due to clinical suspicion, acute dual immunotherapy with steroid and immunoglobulin was given with substantial improvement. Subsequently, the existence of anti-LGI1 antibodies in cerebrospinal fluid was confirmed. Although both patients received a dose of rituximab during their hospitalization, only the patient in the first case continued biannual doses of rituximab. The second patient was not initially considered to continue long-term immunomodulatory treatment and experienced a relapse. Conclusions: These clinical vignettes present the reader with the classic characteristics of this disease. This can facilitate its recognition and timely initiation of treatment, improving the functional prognosis of patients.

Introducción: la encefalitis anti-LGI1 se caracteriza por un patrón de inflamación que afecta de forma predominante al sistema límbico. Forma parte de las encefalitis autoinmunes que atacan a antígenos de superficie neuronal. Se caracteriza por la tríada de demencia subaguda, crisis distónicas faciobraquiales e hiponatremia, presentando una respuesta excelente a la inmunoterapia. El objetivo de este trabajo es describir por casos clínicos la evolución clínica y resultado funcional a 6 meses de dos pacientes con encefalitis anti-LGI1. Casos clínicos: caso 1: hombre de 62 años con cuadro de 8 semanas, manifestado por cambios en el estado de ánimo, desorientación y crisis focales motoras. Caso 2: mujer de 72 años con una evolución de 5 meses de demencia rápidamente progresiva, hiponatremia e hiperintensidades bitemporales en RMN. En ambos, ante la sospecha clínica, se otorgó inmunoterapia dual aguda con esteroide e inmunoglobulina con mejoría sustancial, posteriormente se corroboró la existencia de anticuerpos anti-LGI1 en líquido cefalorraquídeo. Pese a que ambos pacientes recibieron una dosis de rituximab durante su hospitalización, solo el primer caso continuó dosis semestrales de rituximab. El segundo no fue considerado inicialmente para continuar con tratamiento inmunomodulador a largo plazo y presentó una recaída. Conclusiones: estos casos, presentan al lector las características clásicas de esta enfermedad. Esto puede facilitar su reconocimiento y la instauración oportuna del tratamiento, mejorando el pronóstico funcional de los pacientes.

TP53 mutations predict for poor outcomes in patients with newly diagnosed aggressive B-cell lymphomas in the current era.

Genetic subgroups of diffuse large B-cell lymphoma (DLBCL) have been identified through comprehensive genomic analysis; however, it is unclear whether this can be applied in clinical practice. We assessed whether mutations detected by clinical laboratory mutation analysis (CLMA) were predictive of outcomes in patients with newly diagnosed DLBCL/high-grade B-cell lymphoma (HGBL). Patients diagnosed from 2018 to 2022 whose biopsy samples were subjected to CLMA and who received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone or rituximab plus etoposide, prednisolone, vincristine, cyclophosphamide, and doxorubicin were analyzed for overall/complete response rate (ORR/CRR) and estimated progression-free/overall survival (PFS/OS). CLMA was successfully performed in 117 of 122 patient samples (96%), with a median turnaround time of 17 days. Median duration of follow-up was 31.3 months. Of the mutations detected in ≥10% of the samples, only TP53 was associated with both progression and death at 2 years. TP53 mutations were detected in 36% of tumors, and patients with TP53 mutations experienced significantly lower ORR (71% vs 90%; P = .009), CRR (55% vs 77%; P = .01), 2-year PFS (57% vs 77%; P = .006), 2-year OS (70% vs 91%; P = .001), and median OS after relapse (6.1 months vs not yet reached; P = .001) as than those without TP53 mutations. Furthermore, patients with TP53 loss-of-function (LOF) mutations experienced lower rates of 2-year PFS/OS than those with non-LOF mutations and inferior or near-inferior 2-year PFS if harboring high-risk clinicopathologic features. TP53 mutations identified through CLMA can predict for inferior outcomes in patients with newly diagnosed DLBCL/HGBL. Results of CLMA can be used in real time to inform prognosis and/or identify candidates for clinical trials.