RESUMO
Immune checkpoint inhibitors (ICIs) have emerged as the newest pillar of cancer treatment. Immune-mediated toxicities, stemming from increased activity within the T cell lineage, range from asymptomatic or mild complications to those that are fulminant and potentially fatal. Although they are of variable occurrence, cardiovascular, rheumatic, and renal immune-mediated toxicities are among the most serious of these adverse events. We present MASCC recommendations with respect to the workup and management of cardiovascular, rheumatic, and renal immune-mediated toxicities with a focus on presentations that require treatment with immunomodulating agents.
Assuntos
Doenças Cardiovasculares/terapia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/terapia , Inibidores de Checkpoint Imunológico/efeitos adversos , Imunoterapia/efeitos adversos , Nefropatias/terapia , Doenças Reumáticas/terapia , Antígeno CTLA-4/antagonistas & inibidores , Antígeno CTLA-4/imunologia , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , História do Século XXI , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/uso terapêutico , Agências Internacionais/organização & administração , Agências Internacionais/normas , Nefropatias/induzido quimicamente , Nefropatias/epidemiologia , Neoplasias/epidemiologia , Neoplasias/imunologia , Neoplasias/terapia , Cuidados Paliativos/organização & administração , Cuidados Paliativos/normas , Medicina Paliativa/organização & administração , Medicina Paliativa/normas , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Doenças Reumáticas/induzido quimicamente , Doenças Reumáticas/epidemiologia , Índice de Gravidade de Doença , Sociedades Médicas/organização & administração , Sociedades Médicas/normasRESUMO
PURPOSE OF REVIEW: This review summarizes the current evidence on inflammatory arthritis following cancer treatment with immune checkpoint inhibitors (ICI), and the effects of these therapies in patients with preexisting autoimmune arthritis. RECENT FINDINGS: As the use of ICI for cancer therapy continues to expand, a myriad of immune-related adverse events (irAE) caused by these therapies are being recognized. Arthritis has been increasingly reported as a de novo irAE, presenting sometimes as a well defined disorder, such as rheumatoid arthritis or psoriatic arthritis, and in other occasions as undifferentiated monoarthritis, oligoarthritis, or polyarthritis. Remitting seronegative symmetric synovitis with pitting edema (RS3PE) and tenosynovitis have also been reported. Most published cases are reported as mild to moderate in severity. The most common treatment for arthritis has been systemic corticosteroids, although several patients have been treated with traditional disease-modifying antirheumatic drugs (DMARD), and a few, with biologic DMARD. SUMMARY: Arthritis following ICI therapy is pleomorphic. Prompt identification and treatment are imperative to achieve optimal outcomes. Management should be multidisciplinary, including rheumatologists and oncologists, to ensure prompt symptomatic and functional management and continuation of cancer therapy as appropriate.
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Antineoplásicos Imunológicos/efeitos adversos , Artrite/etiologia , Neoplasias/tratamento farmacológico , HumanosRESUMO
OBJECTIVES: To analyse the worldwide occurrence of sicca/Sjögren's (SS) syndrome associated with the use of immune checkpoint inhibitors (ICI) in patients with cancer. METHODS: The ImmunoCancer International Registry (ICIR) is a Big Data-Sharing multidisciplinary network composed by 40 specialists in Rheumatology, Internal Medicine, Immunology and Oncology from 18 countries focused on the clinical and basic research of the immune-related adverse events (irAEs) related to cancer immunotherapies. For this study, patients who were investigated for a clinical suspicion of SS after being exposed to ICI were included. RESULTS: We identified 26 patients (11 women and 15 men, with a mean age at diagnosis of 63.57 years). Underlying cancer included lung (n=12), renal (n=7), melanoma (n=4), and other (n=3) neoplasia. Cancer immunotherapies consisted of monotherapy (77%) and combined regimens (23%). In those patients receiving monotherapy, all patients were treated with PD-1/PD-L1 inhibitors (nivolumab in 9, pembrolizumab in 7 and durvalumab in 4); no cases associated with CTLA-4 inhibitors were identified. The main SS-related features consisted of dry mouth in 25 (96%) patients, dry eye in 17 (65%), abnormal ocular tests in 10/16 (62%) and abnormal oral diagnostic tests in 12/14 (86%) patients. Minor salivary gland biopsy was carried out in 15 patients: histopathological findings consisted of mild chronic sialadenitis in 8 (53%) patients and focal lymphocytic sialadenitis in the remaining 7 (47%); a focus score was measured in 5 of the 6 patients (mean of 1.8, range 1-4). Immunological markers included positive ANA in 13/25 (52%), anti-Ro/ SS-A in 5/25 (20%), RF in 2/22 (9%), anti-La/SS-B in 2/25 (8%), low C3/C4 levels in 1/17 (6%) and positive cryoglobulins in 1/10 (10%). Classification criteria for SS were fulfilled by 10 (62%) out of 16 patients in whom the two key classificatory features were carried out. Among the 26 patients, there were only 3 (11%) who presented exclusively with sicca syndrome without organ-specific autoimmune manifestations. Therapeutic management included measures directed to treat sicca symptoms and therapies against autoimmune-mediated manifestations (glucocorticoids in 42%, second/third-line therapies in 31%); therapeutic response for systemic features was observed in 8/11 (73%). No patient died due to autoimmune involvement. CONCLUSIONS: Patients with Sjögren's syndrome triggered by ICI display a very specific profile different from that reported in idiopathic primary SS, including more frequent occurrence in men, a higher mean age, a predominant immunonegative serological profile, and a notable development of organ-specific autoimmune involvement in spite of the poor immunological profile. The close association found between sicca/Sjögren's syndrome and primarily PD-1 blockade requires further specific investigation.
Assuntos
Antígeno B7-H1 , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Síndrome de Sjogren , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Glândulas Salivares Menores , Síndrome de Sjogren/imunologiaRESUMO
OBJECTIVES: To describe treatment patterns and estimate outcomes among real-world small cell lung cancer (SCLC) patients in the US who received three or more lines of therapy. MATERIALS AND METHODS: We conducted a retrospective analysis of adult patients with SCLC who received a front-line platinum-based regimen and two additional lines of therapy (ie., a cohort of at least three lines of therapy). De-identified patients were selected from a United States Flatiron Health oncology database of electronic health records. Treatment patterns were captured by line of therapy. Outcomes evaluated by line of therapy included real-world overall survival (rwOS), real-world progression free survival (rwPFS), real-world response rate (rwRR) and real-world duration of response (rwDOR). RESULTS: The analysis included 326 3L SCLC patients, of which 103 (32â¯%) received 4L treatment, and 38â¯% (39/103) of 4L treated received 5L of therapy. Among the 3L cohort, the average age was 67â¯years, 49â¯% were male, and nearly all had a history of smoking (96â¯%). In the 3L setting, the median rwOS was 5.3â¯months (95â¯% Confidence Interval (CI): 4.5, 6.0), median rwPFS was 2.5â¯months (95â¯% CI: 2.1, 2.7), rwRR was 19.3â¯% (95â¯% CI: 15.2, 24.0) and median DOR was 3.4â¯months (95â¯% CI: 2.8, 4.4). No differences were seen in outcomes between the overall cohort and a subgroup of patients treated with front-line platinum-based regimen with an anti-programmed cell death ligand 1 (PD-L1) agent (atezolizumab or durvalumab), in each respective line of therapy. CONCLUSION: Results from this large, real-world study of US patients with SCLC in the 3L setting and beyond highlight the poor treatment outcomes in advanced SCLC patients with existing therapies and underscore the dire need for new therapies for SCLC patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/patologia , Masculino , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Feminino , Idoso , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resultado do Tratamento , Taxa de Sobrevida , Adulto , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Cancer patients with autoimmune disease have been excluded from randomized trials of immune checkpoint blockers (ICBs). We conducted a systematic review of observational studies and uncontrolled trials including cancer patients with pre-existing autoimmune disease who received ICBs. METHODS: We searched 5 electronic databases through November 2023. Study selection, data collection, and quality assessment were performed independently by 2 investigators. We performed a meta-analysis to pool incidence of immune-related adverse events (irAEs), including de novo events and flares of existing autoimmune disease, hospitalizations due to irAEs, as well as deaths. RESULTS: A total of 95 studies were included (23,897 patients with cancer and preexisting autoimmune disease). The most common cancer evaluated was lung cancer (30.7 %) followed by skin cancer (15.7 %). Patients with autoimmune disease were more likely to report irAEs compared to patients without autoimmune disease (relative risk 1.3, 95 % CI 1.0 to 1.6). The pooled occurrence rate of any irAEs (flares or de novo) was 61 % (95 % CI 54 % to 68 %); that of flares was 36 % (95 % CI 30 % to 43 %), and that of de novo irAEs was 23 % (95 % CI 16 % to 30 %). Flares were mild (grade <3) in half of cases and more commonly reported in patients with psoriasis/psoriatic arthritis (39 %), inflammatory bowel disease (37 %), and rheumatoid arthritis (36 %). 32 % of the patients with irAEs required hospitalization and treatment of irAEs included corticosteroids in 72 % of the cases. The irAEs mortality rate was 0.07 %. There were no statistically significant differences in cancer response to ICBs between patients with and without autoimmune disease. CONCLUSIONS: Although more patients with pre-existing autoimmune disease had irAEs, these were mild and managed with corticosteroids in most cases, with no impact on cancer response. These results suggest that ICBs can be used in these patients, but careful monitoring is required, as over a third of the patients will experience a flare of their autoimmune disease and/or require hospitalization. These findings provide a crucial foundation for oncologists to refine their monitoring and management strategies, ensuring that the benefits of ICB therapy are maximized while minimizing its risks.
Assuntos
Doenças Autoimunes , Inibidores de Checkpoint Imunológico , Neoplasias , Estudos Observacionais como Assunto , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/complicações , Neoplasias/tratamento farmacológicoAssuntos
Cálcio da Dieta , Cálcio , Adulto , Suplementos Nutricionais , Fraturas Ósseas , Humanos , Vitamina DRESUMO
OBJECTIVE: Patients with cancer and systemic lupus erythematosus (SLE) may have worse outcomes than those without SLE, given their comorbidities. We examined survival in elderly women with breast cancer (BC) and SLE and hypothesized that survival would be decreased compared with women with BC but without SLE. METHODS: We identified patients with BC and SLE and patients with BC without SLE in the Texas Cancer Registry and Surveillance, Epidemiology, and End Results, linked to Medicare claims. Overall survival (OS) was estimated after matching (age and cancer stage) and in multivariable Cox proportional hazards models adjusting for other cancer characteristics, treatment, and comorbidities. Two additional cohorts of women without cancer with and without SLE were also studied. RESULTS: We identified 494 BC SLE cases and 145,517 BC non-SLE cases, of whom we matched 9,708. Women with SLE were less likely to receive radiation, breast conserving surgery, or endocrine therapy. The 8-year OS estimate for women with early BC (stages 0-II) with and without SLE was 52% (95% confidence interval [95% CI] 45%-59%) and 74% (95% CI 73%-75%), respectively. In the Cox multivariable model, BC and SLE had increased risk of death (hazard ratio [HR] 1.65, 95% CI 1.38-1.98). Women with BC and SLE also had increased risk of death compared with women with SLE but without cancer (HR 1.42, 95% CI 1.05-1.92) after adjusting for SLE severity. Women with SLE and BC received less glucocorticoids, antimalarials, and immunosuppressants after cancer diagnosis than those without cancer. CONCLUSION: Systemic lupus is a risk factor for increased mortality in women with early BC.
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Neoplasias da Mama , Lúpus Eritematoso Sistêmico , Humanos , Feminino , Idoso , Estados Unidos/epidemiologia , Neoplasias da Mama/terapia , Medicare , Incidência , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/terapia , Lúpus Eritematoso Sistêmico/epidemiologia , Fatores de Risco , Modelos de Riscos ProporcionaisRESUMO
BACKGROUND: Delta-like ligand 3 (DLL3), a member of the Notch pathway, has been identified as a potential therapeutic target as it is highly expressed in small cell lung cancer (SCLC), a subtype accounting for 15% of lung cancer cases. OBJECTIVE: A systematic literature review (SLR) was conducted to understand the prevalence and prognostic impact of DLL3 expression on survival of patients with SCLC and treatment response. PATIENTS AND METHODS: Systematic literature searches were conducted across multiple databases to capture studies of any SCLC population that evaluated DLL3 expression. Specific outcomes of interest included prevalence of DLL3 expression, method of expression analysis, and impact on outcome, including treatment response and survival (overall, progression-free, disease-free) according to varying levels of DLL3 expression/positivity. Standard risk of bias tools were used to evaluate study quality. RESULTS: Among the 30 included studies, the most common DLL3 testing method was immunohistochemistry (N = 26, 86.7%). For comparability, results focused on the 13 (22.3%) studies that used the Ventana DLL3 (SP347) immunohistochemistry assay. The prevalence of DLL3 positivity ranged from 80.0-93.5% for studies using a threshold of ≥ 1% of tumor cells (N = 4) and 58.3-91.1% for studies with a ≥ 25% threshold (N = 4). DLL3 expression was generally categorized as high using cutoffs of ≥ 50% (prevalence range: 45.8-79.5%; N = 6) or ≥ 75% (prevalence range: 47.3-75.6%; N = 5) of cells with positivity. Two studies used an H-score of ≥ 150 to define high DLL3 expression with prevalence ranging from 33.3-53.1%. No consistent associations were seen between DLL3 expression level and patient age, sex, smoking history, or disease stage. Two studies reported change in DLL3 expression category (high versus low) before and after chemotherapy. No statistically significant differences were reported between DLL3 expression groups and survival (overall, progression-free, or disease-free) or treatment response. CONCLUSIONS: There is a high prevalence of DLL3 expression in SCLC. Further research and analytical methods may help to characterize different populations of patients with SCLC based on DLL3 expression. While no significant prognostic factor in the included studies was identified, additional cohort studies using standardized methodology, with longer follow-up, are needed to better characterize any potential differences in patient survival or response by DLL3 expression level in SCLC.
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Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Prognóstico , Ligantes , Prevalência , Proteínas de Membrana/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/uso terapêuticoRESUMO
Importance: Bone health screening is recommended for patients with prostate cancer who are initiating treatment with androgen deprivation therapy (ADT); however, bone mineral density screening rates in the US and their association with fracture prevention are unknown. Objective: To assess dual-energy x-ray absorptiometry (DXA) screening rates and their association with fracture rates among older men with prostate cancer initiating treatment with androgen deprivation therapy. Design, Setting, and Participants: This retrospective nationwide population-based cohort study used data from the Surveillance, Epidemiology, and End Results database and the Texas Cancer Registry linked with Medicare claims. Participants comprised 54 953 men 66 years or older with prostate cancer diagnosed between January 2005 and December 2015 who initiated treatment with ADT. Data were censored at last enrollment in Medicare and analyzed from January 1 to September 30, 2021. Exposures: Dual-energy x-ray absorptiometry screening within 12 months before and 6 months after the first ADT claim. Main Outcomes and Measures: Frequencies of DXA screening and fracture (any fracture and major osteoporotic fracture) and overall survival were calculated. The association between DXA screening and fracture was evaluated using a multivariable Cox proportional hazards model with propensity score adjustment. Results: Among 54â¯953 men (median age, 74 years; range, 66-99 years) with prostate cancer, 4689 (8.5%) were Hispanic, 6075 (11.1%) were non-Hispanic Black, 41 453 (75.4%) were non-Hispanic White, and 2736 (5.0%) were of other races and/or ethnicities (including 121 [0.2%] who were American Indian or Alaska Native; 1347 [2.5%] who were Asian, Hawaiian, or Pacific Islander; and 1268 [2.3%] who were of unknown race/ethnicity). Only 4362 men (7.9%) received DXA screening. The DXA screening rate increased from 6.8% in 2005 to 8.4% in 2015. Lower screening rates were associated with being single (odds ratio [OR], 0.89; 95% CI, 0.81-0.97; P = .01) and non-Hispanic Black (OR, 0.80; 95% CI, 0.70-0.91; P < .001), living in small urban areas (OR, 0.77; 95% CI, 0.66-0.90; P = .001) and areas with lower educational levels (OR, 0.75; 95% CI, 0.67-0.83; P < .001), and receiving nonsteroidal androgens (OR, 0.57; 95% CI, 0.39-0.84; P = .004). Overall, 9365 patients (17.5%) developed fractures after initial receipt of ADT. The median time to first fracture was 31 months (IQR, 15-56 months). In the multivariable model with propensity score adjustment, DXA screening was not associated with fracture risk at any site (hazard ratio [HR], 0.96; 95% CI, 0.89-1.04; P = .32) among men without previous fractures before receipt of ADT. However, previous DXA screening was associated with a decreased risk of major fractures (HR, 0.91; 95% CI, 0.83-1.00; P = .05) after propensity score adjustment. Conclusions and Relevance: In this study, low DXA screening rates were observed among older men with localized or regional prostate cancer after initiation of treatment with ADT. Despite low rates of screening, evaluation of bone mineral density with a DXA scan was associated with lower risk of major fractures. These findings suggest that DXA screening is important for the prevention of major fractures among older men with prostate cancer and that implementation strategies are needed to adopt bone health screening guidelines in clinical practice.
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Osteoporose , Fraturas por Osteoporose , Neoplasias da Próstata , Idoso , Antagonistas de Androgênios/efeitos adversos , Androgênios/uso terapêutico , Densidade Óssea , Estudos de Coortes , Humanos , Masculino , Medicare , Osteoporose/diagnóstico , Osteoporose/epidemiologia , Osteoporose/etiologia , Neoplasias da Próstata/epidemiologia , Estudos Retrospectivos , Estados Unidos/epidemiologiaRESUMO
Bone disease is common in patients with multiple myeloma (MM), which manifests as bone pain and skeletal-related events (SREs) such as pathological fractures and spinal cord compression. Myeloma bone disease (MBD) can adversely affect the quality of life of patients and have negative effects on morbidity and mortality. The pathogenesis of MBD is complex, and several factors are involved in the dysregulation of bone metabolism and uncoupling of bone remodeling, which result in net bone loss and devastating SREs. Broadly speaking, elevated osteoclast activity, suppressed osteoblast activity, and an aberrant marrow microenvironment play a role in MBD. Interaction of MM cells with the main bone cell osteocytes also promote further bone destruction. This review focuses on the role of bone-modifying agents in the prevention and treatment of MBD. The mainstay of MBD prevention are antiresorptive agents, bisphosphonates and denosumab. However, these agents do not play a direct role in bone formation and repair of existing MBD. Newer agents with anabolic effects such as anti-sclerostin antibodies, parathyroid hormone, anti-Dickkopf-1 antibodies, and others have shown potential in repair of MBD lesions. With the development of several new agents, the treatment landscape of MBD is likely to evolve in the coming years. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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Aim: To evaluate adverse events in cancer patients with pre-existing sarcoidosis receiving immune checkpoint inhibitors (ICIs). Patients & methods: We retrospectively reviewed cancer patients with sarcoidosis who underwent treatment with ICI to determine frequency of sarcoidosis flares. Results: 32 patients with sarcoidosis received ICIs The median time to ICI initiation was 7 years (range: 1 month to 51 years). One patient (3%) with a 20-year remote history of sarcoidosis developed a clinically symptomatic exacerbation after three doses of atezolizumab, with hilar lymphadenopathy, subcutaneous nodules, arthritis and uveitis. Atezolizumab was discontinued and prednisone initiated. She had a fluctuating course with two additional flares. Conclusion: Frequency of flares in patients with a remote history of sarcoidosis who receive ICIs is low.
Lay summary Immune checkpoint inhibitors have revolutionized the treatment of cancer. However, because they increase patients' immune responses, they can cause inflammatory and autoimmune adverse events. There are some concerns that patients with cancer who have pre-existing autoimmune or inflammatory disorders may flare when they receive these agents. We report 32 patients with cancer who had a history of sarcoidosis and received immune checkpoint inhibitors. Of these, only one had a flare of sarcoidosis and the patient required treatment. Our findings suggest that most cancer patients with a remote history of sarcoidosis can receive immune checkpoint inhibitors without experiencing sarcoidosis flares.
Assuntos
Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Sarcoidose/complicações , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Exacerbação dos SintomasRESUMO
OBJECTIVE: To estimate the incidence of immune checkpoint inhibitor-related myositis (ICI-myositis) in cancer patients receiving ICIs, and to report associated clinical manifestations, patterns of care, and outcomes. METHODS: We identified a retrospective cohort of patients receiving ICIs between 2016 and 2019 seen at the University of Texas MD Anderson Cancer Center. Cases of ICI-myositis were identified using International Classification of Disease codes and confirmed by reviewing medical records and pathology, as available. RESULTS: A total of 9,088 patients received an ICI. Thirty-six patients (0.40%) were identified as having ICI-myositis: 17 patients (47%) with ICI-myositis alone and 19 (53%) with overlap manifestations (5 patients with myocarditis, 5 with myasthenia gravis, and 9 with both). The incidence of ICI-myositis was 0.31% in those receiving ICI monotherapy and 0.94% in those receiving combination ICI therapy (relative risk 3.1 [95% confidence interval 1.5-6.1]). Twenty-five patients (69%) received ≥1 treatment in addition to glucocorticoids: plasmapheresis in 17 patients (47%), intravenous immunoglobulin in 12 (33%), and biologics in 11 (31%). Patients with overlap conditions had worse outcomes than those with myositis alone, and 79% of them developed respiratory failure. Eight patients died as a result of ICI-myositis, and all had overlap syndrome with myasthenia gravis or myocarditis (P < 0.05); 75% of these patients had a concomitant infection. CONCLUSION: ICI-myositis is a rare but severe adverse event. More than half of the patients presented with overlap manifestations and had deleterious outcomes, including respiratory failure and death. None of the patients with ICI-myositis alone died as a result of adverse events. Optimal treatment strategies have yet to be determined.
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Inibidores de Checkpoint Imunológico/efeitos adversos , Miastenia Gravis/induzido quimicamente , Miocardite/induzido quimicamente , Miosite/induzido quimicamente , Neoplasias/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Infecções/epidemiologia , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/epidemiologia , Miastenia Gravis/mortalidade , Miocardite/epidemiologia , Miocardite/mortalidade , Miosite/epidemiologia , Miosite/mortalidade , Insuficiência Respiratória/epidemiologia , Insuficiência Respiratória/etiologia , Estudos RetrospectivosRESUMO
OBJECTIVE: To determine rates of cervical cancer screening and associated abnormal results in women with systemic lupus erythematosus (SLE). METHODS: We identified women with an initial diagnosis of SLE in the MarketScan Commercial Claims and Encounters Database from 2001 to 2014. Cervical cancer screening rates and associated diagnostic claims within 3 years of the initial claim were determined. Multivariable logistic regression was performed to evaluate the association of screening with lupus treatment. A matched logistic regression analysis was conducted to compare screening rates to those in age-matched women without connective tissue disease. RESULTS: We included 4,316 women with SLE. Screening rates were higher in women with SLE than in general controls (73.4% versus 58.5%; P < 0.001). Factors associated with decreased screening included recent time (odds ratio [OR] 0.70 [95% confidence interval (95% CI)] 0.55-0.89) (2012-2014 compared to 2001-2005), age ≥61 years (OR 0.27 [95% CI 0.18-0.39]), comorbidity score ≥2 (OR 0.71 [95% CI 0.6-0.83]), corticosteroid use (OR 0.77 [95% CI 0.61-0.97]), and use of immunosuppressants (OR 0.80 [95% CI 0.69-0.94]). Abnormal pathology result claims were more common in women with SLE than in general controls (12.3% versus 9.8%; P < 0.001). CONCLUSION: Though with higher rates than the general cohort, over 25% of the patients with SLE were not screened, and screening rates seem to be decreasing over time. Patients with SLE are at higher risk of abnormal cervical screening test results than controls, supporting the need for regular screening.
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Detecção Precoce de Câncer/estatística & dados numéricos , Lúpus Eritematoso Sistêmico , Neoplasias do Colo do Útero/diagnóstico , Esfregaço Vaginal/estatística & dados numéricos , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVE: To analyse the clinical patterns of sarcoidosis triggered by immune checkpoint inhibitors (ICIs) in patients with cancer. PATIENTS AND METHODS: The ImmunoCancer International Registry is a big data-sharing multidisciplinary network from 18 countries dedicated to evaluating the clinical research of immune-related adverse events related to cancer immunotherapies. RESULTS: We identified 32 patients with biopsy-proven sarcoidosis. Underlying cancer included mainly melanoma (n = 24). Cancer immunotherapy consisted of monotherapy in 19 cases (anti-PD-1 in 18 and ipilimumab in 1) or combined ipilimumab + nivolumab in 13. The time median interval between initiation of ICI and sarcoidosis diagnosis was 3 months (range, 2-29 months). The use of combined ICI was associated with a shorter delay in developing sarcoidosis symptoms. The disease was symptomatic in 19 (59%) cases with mostly cutaneous, respiratory and general symptoms. The organs involved included mainly the mediastinal lymph nodes (n = 32), the lungs (n = 11), the skin (n = 10) and the eyes (n = 5). Pulmonary computed tomography studies showed bilateral hilar lymphadenopathy in all cases. There was no severe manifestation. Specific systemic therapy was required in only 12 patients (37%): oral glucocorticoids in 9, and hydroxychloroquine in 3. ICIs were held in 25 patients (78%) and definitively discontinued in 18 (56%) patients. Seven patients continued ICI treatment with a second flare in one case. In six additional patients, an ICI was reintroduced with no harm, and sarcoidosis relapsed in one of them. CONCLUSION: Our study shows that ICI-related sarcoidosis seems to have a specific profile, possibly more benign than that of idiopathic sarcoidosis, and does not necessarily imply ICI discontinuation.
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Inibidores de Checkpoint Imunológico/administração & dosagem , Imunoterapia/efeitos adversos , Sarcoidose/induzido quimicamente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Biópsia , Feminino , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Ipilimumab/efeitos adversos , Ipilimumab/uso terapêutico , Pulmão/efeitos dos fármacos , Linfonodos/efeitos dos fármacos , Masculino , Melanoma/tratamento farmacológico , Pessoa de Meia-Idade , Nivolumabe/efeitos adversos , Nivolumabe/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Adulto JovemRESUMO
Management of rheumatoid arthritis (RA) in patients with cancer is complex and requires a multidisciplinary approach. A few studies have examined the risk for recurrence in patients with RA receiving disease-modifying antirheumatic drugs, primarily tumor necrosis factor-α inhibitors. Although these agents seem to be safe in patients with a history of cancer and no evidence of disease, additional information is needed to determine their potential effects in patients with RA and active cancer. Patients with RA undergoing cancer therapy, including surgery, radiation, chemotherapy, and immunotherapy, need to be carefully monitored because they are at increased risk for adverse events.
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Antirreumáticos , Artrite Reumatoide , Neoplasias , Antirreumáticos/efeitos adversos , Antirreumáticos/uso terapêutico , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Detecção Precoce de Câncer , Humanos , Neoplasias/complicações , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Fatores de RiscoRESUMO
INTRODUCTION: Biologic disease-modifying anti-rheumatic drugs (bDMARDs) interfere with the immune system and could theoretically increase risk of malignancies. However, recent evidence has not substantiated such concerns and physicians are less reluctant in treating patients with underlying cancer with such bDMARDs. We aimed to understand the current utilization patterns of bDMARDs for the treatment of rheumatoid arthritis (RA) in cancer patients. METHODS: We performed a retrospective cohort study of patients with prevalent RA and cancer initially seen at MD Anderson Cancer Center between 2002 and 2014. A cohort of cancer patients was identified from the tumor registry, and patients with RA were identified through ICD-9 codes, followed by review of electronic medical records. We included patients 18 years and older, with a cancer diagnosis, and a diagnosis of RA by a rheumatologist. Patients were followed until 2016. RESULTS: We identified 431 patients with RA and cancer that met our inclusion criteria. Overall, 111 (26%) received bDMARDs after their cancer diagnosis; of these, 60 (54%) had received bDMARDs prior to their cancer diagnosis and continued to receive this therapy following their diagnosis. Thirteen (22%) switched to a different bDMARD, and the rest continued to receive the same agent after their cancer diagnosis. Of all patients on a bDMARD, 91 (82%) received tumor necrosis factor inhibitors (TNFi). CONCLUSIONS: The treatment landscape of patients with a history of cancer and RA is changing. Future studies evaluating the safety of bDMARDs in patients with a recent history of cancer or with active cancer are needed. Part of the data of this project was presented as a poster at the 2016 American College of Rheumatology annual meeting. Zamora NV, Siddhanamatha H, Barbo A, Tayar J, Lin H, Suarez-Almazor M. Utilization of Biologic Therapy in Patients with Rheumatoid Arthritis and Cancer [abstract].Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/utilization-of-biologic-therapy-in-patients-with-rheumatoid-arthritis-and-cancer/. Accessed September 30, 2019. Key Points ⢠One in four patients with RA and concomitant cancer received bDMARDs, including TNFi, after their cancer diagnosis, at our institution. ⢠Half of the patients with RA and cancer who received bDMARDs had initiated therapy prior to the cancer diagnosis, continuing thereafter.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Neoplasias/complicações , Padrões de Prática Médica/estatística & dados numéricos , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , TexasRESUMO
INTRODUCTION/OBJECTIVES: The effects of biologic disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) and cancer are largely unknown. We examined overall survival (OS) in patients with RA and solid malignancies receiving bDMARDs. METHODS: We performed a retrospective cohort study of patients with RA and solid malignancies seen at MD Anderson Cancer Center between 2002 and 2014. Cox proportional hazard regression models, stratified by tumor type and stage, were fit evaluating use of bDMARDs as a time fixed and time varying covariate. RESULTS: We identified 431 RA patients with solid malignancies: 111 (26%) received bDMARDs after their cancer diagnosis. Median OS from cancer diagnosis was 16.1 years. Of the patients receiving bDMARDs, most had localized disease, and only 14 (13%) had advanced cancer. In the stratified Cox models no statistically significant differences were observed between patients who received tumor necrosis factor inhibitors (TNFi) or patients who received nonTNFi, compared with those who did not receive bDMARDs (hazard ratio (HR), 0.67; 95% confidence interval (CI), 0.31, 1.44; HR, 1.10; 95% CI, 0.26, 4.60 respectively). In breast cancer patients, those receiving TNFi or nonTNFi had a numerically higher but statistically nonsignificant HR compared with those who did not receive bDMARD: HR, 1.40 (95% CI, 0.42, 4.73), and HR, 1.37 (95% CI, 0.22, 8.42) respectively. CONCLUSION: No significant differences in OS were observed between patients who received bDMARDs and those who did not. Additional data is needed to evaluate other cancer outcomes such as recurrence and progression, and patients with advanced cancer. Key Points â¢We found no statistically significant differences in OS between patients with RA and concomitant solid malignancies who received bDMARDs and those who did not. â¢Most patients who received bDMARDs had been diagnosed with early stage cancer â¢As few patients with advanced cancer received bDMARDs safety for this group cannot be established â¢No significant differences were observed between TNFi and nonTNFi, but the sample size was small.
Assuntos
Antirreumáticos , Artrite Reumatoide , Produtos Biológicos , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Estudos RetrospectivosRESUMO
Recognizing rare but clinically significant toxicity of immunotherapy is critical. Here we describe the first detailed case of severe osteonecrosis of the jaw due to anti-PD-1. A 75-year-old man with metastatic melanoma, with no prior radiation or treatment with bone-targeting agents, experienced jaw pain 1 week after his first dose of nivolumab. Imaging studies were negative, and treatment was resumed after pain was controlled. 4 months later, the patient experienced acute exacerbation of pain and malocclusion of the jaw. Imaging showed bilateral fractures of the angle of mandible with extensive disruption of the normal trabecular architecture, requiring total mandibulectomy. The patient's metastatic melanoma responded to treatment and remains controlled >20 months after treatment cessation without further therapy.
Assuntos
Inibidores de Checkpoint Imunológico/efeitos adversos , Imunoterapia/efeitos adversos , Doenças Maxilomandibulares/induzido quimicamente , Melanoma/tratamento farmacológico , Nivolumabe/efeitos adversos , Osteonecrose/induzido quimicamente , Idoso , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Masculino , Nivolumabe/uso terapêuticoRESUMO
We aimed to study the utility of the FRAX tool in predicting fractures in patient's receiving a hematopoietic stem cell transplantation (HSCT). Our results indicate that the FRAX tool has modest fracture predictive ability in patients greater than 50 years of age at the time of HSCT. PURPOSE: Identifying patients at high risk of osteoporotic fractures following HSCT is challenging. We aimed to evaluate the utility of the FRAX tool at the time of HSCT in predicting fractures following transplant. METHODS: We conducted a retrospective chart review of adults (> 18 years) who underwent HSCT at MD Anderson Cancer Center from January 1, 2001, to December 31, 2010, and were followed until December 31, 2013, to identify osteoporotic fractures. Multivariate Cox regression models were built using FRAX score thresholds of low risk < 10%, medium risk 10 to 20%, and high risk > 20% probability of osteoporotic fracture. RESULTS: We identified 5170 patients who had undergone HSCT, 10% of whom developed an osteoporotic fracture during a median follow-up of 3.2 years. In patients > 65 years of age, those with medium risk (hazard ratio (HR) 2.38, 95% confidence interval (CI) 1.27-4.47) and high risk (HR 3.41, 95% CI 1.73-6.75) had a greater probability of developing an osteoporotic fracture compared to those at low risk. Similar trends were seen in patients 50 to 65 years of age. CONCLUSIONS: In patients greater than 50 years, the FRAX tool has modest predictive ability and could be used to aid in preventive treatment decision-making at the time of transplant.