RESUMO
Minimal residual disease (MRD) is increasingly used as a prognostic biomarker, a measure of clinical efficacy, and a guide for treatment decisions in various hematologic malignancies. We sought to characterize MRD data in registrational trials in hematologic malignancies submitted to the U.S. Food and Drug Administration (FDA) with the ultimate goal of expanding the utility of MRD data in future drug applications. We descriptively analyzed MRD data collected in registrational trials, including the type of MRD endpoint, assay, disease compartment(s) assessed, and the acceptance of MRD data in the U.S. prescribing information (USPI). Of 196 drug applications submitted between January 2014 and February 2021, 55 (28%) included MRD data. Of the 55 applications, MRD data was proposed by the Applicant for inclusion in the USPI in 41 (75%) applications but was included in only 24 (59%). Despite an increasing number of applications that proposed to include MRD data in the USPI, the acceptance rate decreased over time. Although MRD data have the potential to expedite drug development, our analysis identified challenges and specific areas for improvement, including assay validation, standardization of collection methods to optimize performance, and considerations in trial design and statistical methodology.
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Neoplasias Hematológicas , Humanos , Estados Unidos , Preparações Farmacêuticas , Neoplasia Residual/tratamento farmacológico , Neoplasia Residual/patologia , United States Food and Drug Administration , Neoplasias Hematológicas/tratamento farmacológicoRESUMO
INTRODUCTION: The utility of dose escalation after positive positron emission tomography following 2 cycles of ABVD (PET2) for Hodgkin Lymphoma (HL) remains controversial. We describe the United States real-world practice patterns for PET2 positive patients. PATIENTS AND METHODS: Data was collected from 15 sites on PET2 positive HL patients after receiving frontline treatment between January, 2015 and June, 2019. Descriptive analyses between those with therapy change and those continuing initial therapy were assessed. RESULTS: A total of 129 patients were identified; 111 (86%) were treated with ABVD therapy and 18 (14%) with an alternate regimen. At PET2 assessment, 74.4% (96/129) had Deauville score (DS) 4 and 25.6% (33/129) had DS 5. Of the 66 limited stage (LS) patients with PET2 DS score of 4/5, 77.3% (51/66) continued initial therapy and 22.7% (15/66) changed to escalated therapy. The 12-month progression-free survival (PFS) for DS 4/5 LS patients was 67.0% (95% CI; 54.9-81.7) for patients without escalation compared with 51.4% (95% CI; 30.8-85.8) for those who escalated. Of the 63 DS 4/5 patients with advanced stage (AS) disease, 76.2% (48/63) continued initial therapy and 23.8% (15/63) changed to escalated therapy. The 12-month PFS for DS 4/5 AS patients was 38.3% (95% CI: 26.3%-55.7%) for patients without escalation compared with 57.1% (95% CI: 36.3-89.9) for those with escalation. CONCLUSION: A minority of PET2 positive HL patients undergo therapy escalation and outcomes remain overall suboptimal. Improved prognostics markers and better therapeutics are required to improve outcomes for high-risk PET2 positive HL patients.
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Doença de Hodgkin , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/uso terapêutico , Dacarbazina/uso terapêutico , Doxorrubicina/uso terapêutico , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/patologia , Humanos , Tomografia por Emissão de Pósitrons/métodos , Vimblastina/uso terapêuticoRESUMO
Data addressing prognostication in patients with HIV related Burkitt lymphoma (HIV-BL) currently treated remain scarce. We present an international analysis of 249 (United States: 140; United Kingdom: 109) patients with HIV-BL treated from 2008 to 2019 aiming to identify prognostic factors and outcomes. With a median follow up of 4.5 years, the 3-year progression-free survival (PFS) and overall survival (OS) were 61% (95% confidence interval [CI] 55% to 67%) and 66% (95%CI 59% to 71%), respectively, with similar results in both countries. Patients with baseline central nervous system (CNS) involvement had shorter 3-year PFS (36%) compared to patients without CNS involvement (69%; P < .001) independent of frontline treatment. The incidence of CNS recurrence at 3 years across all treatments was 11% with a higher incidence observed after dose-adjusted infusional etoposide, doxorubicin, vincristine, prednisone, cyclophosphamide (DA-EPOCH) (subdistribution hazard ratio: 2.52; P = .03 vs other regimens) without difference by CD4 count 100/mm3. In multivariate models, factors independently associated with inferior PFS were Eastern Cooperative Oncology Group (ECOG) performance status 2-4 (hazard ratio [HR] 1.87; P = .007), baseline CNS involvement (HR 1.70; P = .023), lactate dehydrogenase >5 upper limit of normal (HR 2.09; P < .001); and >1 extranodal sites (HR 1.58; P = .043). The same variables were significant in multivariate models for OS. Adjusting for these prognostic factors, treatment with cyclophosphamide, vincristine, doxorubicin, and high-dose methotrexate, ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) was associated with longer PFS (adjusted HR [aHR] 0.45; P = .005) and OS (aHR 0.44; P = .007). Remarkably, HIV features no longer influence prognosis in contemporaneously treated HIV-BL.
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Linfoma de Burkitt , Infecções por HIV , Linfoma de Burkitt/diagnóstico , Linfoma de Burkitt/tratamento farmacológico , Linfoma de Burkitt/epidemiologia , Intervalo Livre de Doença , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Recidiva Local de Neoplasia , Rituximab , Reino Unido , Estados Unidos/epidemiologiaRESUMO
Central nervous system (CNS) involvement in Burkitt lymphoma (BL) poses a major therapeutic challenge, and the relative ability of contemporary regimens to treat CNS involvement remains uncertain. We described prognostic significance of CNS involvement and incidence of CNS recurrence/progression after contemporary immunochemotherapy using real-world clinicopathologic data on adults with BL diagnosed between 2009 and 2018 across 30 US institutions. We examined associations between baseline CNS involvement, patient characteristics, complete response (CR) rates, and survival. We also examined risk factors for CNS recurrence. Nineteen percent (120/641) of patients (age 18-88 years) had CNS involvement. It was independently associated with HIV infection, poor performance status, involvement of ≥2 extranodal sites, or bone marrow involvement. First-line regimen selection was unaffected by CNS involvement (P=0.93). Patients with CNS disease had significantly lower rates of CR (59% versus 77% without; P<0.001), worse 3-year progression-free survival (adjusted hazard ratio [aHR], 1.53, 95% confidence interval [CI], 1.14-2.06, P=0.004) and overall survival (aHR, 1.62, 95%CI, 1.18-2.22, P=0.003). The 3-year cumulative incidence of CNS recurrence was 6% (95%CI, 4-8%). It was significantly lower among patients receiving other regimens (CODOX-M/IVAC, 4%, or hyperCVAD/MA, 3%) compared with DA-EPOCH-R (13%; adjusted sub-HR, 4.38, 95%CI, 2.16-8.87, P<0.001). Baseline CNS involvement in BL is relatively common and portends inferior prognosis independent of first-line regimen selection. In real-world practice, regimens with highly CNS-penetrant intravenous systemic agents were associated with a lower risk of CNS recurrence. This finding may be influenced by observed suboptimal adherence to the strict CNS staging and intrathecal therapy procedures incorporated in DA-EPOCH-R.
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Linfoma de Burkitt , Neoplasias do Sistema Nervoso Central , Infecções por HIV , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Burkitt/diagnóstico , Linfoma de Burkitt/tratamento farmacológico , Linfoma de Burkitt/epidemiologia , Sistema Nervoso Central , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/epidemiologia , Estudos de Coortes , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/uso terapêutico , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Rituximab/uso terapêutico , Adulto JovemRESUMO
PURPOSE: Burkitt lymphoma (BL) has unique biology and clinical course but lacks a standardized prognostic model. We developed and validated a novel prognostic index specific for BL to aid risk stratification, interpretation of clinical trials, and targeted development of novel treatment approaches. METHODS: We derived the BL International Prognostic Index (BL-IPI) from a real-world data set of adult patients with BL treated with immunochemotherapy in the United States between 2009 and 2018, identifying candidate variables that showed the strongest prognostic association with progression-free survival (PFS). The index was validated in an external data set of patients treated in Europe, Canada, and Australia between 2004 and 2019. RESULTS: In the derivation cohort of 633 patients with BL, age ≥ 40 years, performance status ≥ 2, serum lactate dehydrogenase > 3× upper limit of normal, and CNS involvement were selected as equally weighted factors with an independent prognostic value. The resulting BL-IPI identified groups with low (zero risk factors, 18% of patients), intermediate (one factor, 36% of patients), and high risk (≥ 2 factors, 46% of patients) with 3-year PFS estimates of 92%, 72%, and 53%, respectively, and 3-year overall survival estimates of 96%, 76%, and 59%, respectively. The index discriminated outcomes regardless of HIV status, stage, or first-line chemotherapy regimen. Patient characteristics, relative size of the BL-IPI groupings, and outcome discrimination were consistent in the validation cohort of 457 patients, with 3-year PFS estimates of 96%, 82%, and 63% for low-, intermediate-, and high-risk BL-IPI, respectively. CONCLUSION: The BL-IPI provides robust discrimination of survival in adult BL, suitable for use as prognostication and stratification in trials. The high-risk group has suboptimal outcomes with standard therapy and should be considered for innovative treatment approaches.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Burkitt/tratamento farmacológico , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Adulto , Austrália , Canadá , Estudos de Coortes , Europa (Continente) , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Avaliação de Resultados em Cuidados de Saúde/métodos , Prognóstico , Rituximab/administração & dosagem , Estados UnidosRESUMO
We examined adults with untreated Burkitt lymphoma (BL) from 2009 to 2018 across 30 US cancer centers. Factors associated with progression-free survival (PFS) and overall survival (OS) were evaluated in univariate and multivariate Cox models. Among 641 BL patients, baseline features included the following: median age, 47 years; HIV+, 22%; Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2 to 4, 23%; >1 extranodal site, 43%; advanced stage, 78%; and central nervous system (CNS) involvement, 19%. Treatment-related mortality was 10%, with most common causes being sepsis, gastrointestinal bleed/perforation, and respiratory failure. With 45-month median follow-up, 3-year PFS and OS rates were 64% and 70%, respectively, without differences by HIV status. Survival was better for patients who received rituximab vs not (3-year PFS, 67% vs 38%; OS, 72% vs 44%; P < .001) and without difference based on setting of administration (ie, inpatient vs outpatient). Outcomes were also improved at an academic vs community cancer center (3-year PFS, 67% vs 46%, P = .006; OS, 72% vs 53%, P = .01). In multivariate models, age ≥ 40 years (PFS, hazard ratio [HR] = 1.70, P = .001; OS, HR = 2.09, P < .001), ECOG PS 2 to 4 (PFS, HR = 1.60, P < .001; OS, HR = 1.74, P = .003), lactate dehydrogenase > 3× normal (PFS, HR = 1.83, P < .001; OS, HR = 1.63, P = .009), and CNS involvement (PFS, HR = 1.52, P = .017; OS, HR = 1.67, P = .014) predicted inferior survival. Furthermore, survival varied based on number of factors present (0, 1, 2 to 4 factors) yielding 3-year PFS rates of 91%, 73%, and 50%, respectively; and 3-year OS rates of 95%, 77%, and 56%, respectively. Collectively, outcomes for adult BL in this real-world analysis appeared more modest compared with results of clinical trials and smaller series. In addition, clinical prognostic factors at diagnosis identified patients with divergent survival rates.
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Linfoma de Burkitt/sangue , Linfoma de Burkitt/tratamento farmacológico , Adulto , Idoso , Linfoma de Burkitt/genética , Feminino , Rearranjo Gênico/genética , Humanos , Estimativa de Kaplan-Meier , L-Lactato Desidrogenase/sangue , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Proteínas Proto-Oncogênicas c-myc/genética , Resultado do Tratamento , Estados UnidosRESUMO
PURPOSE: Venetoclax-based therapy is a standard-of-care option in first-line and relapsed/refractory chronic lymphocytic leukemia (CLL). Patient management following venetoclax discontinuation remains nonstandard and poorly understood. EXPERIMENTAL DESIGN: To address this, we conducted a large international study to identify a cohort of 326 patients who discontinued venetoclax and have been subsequently treated. Coprimary endpoints were overall response rate (ORR) and progression-free survival for the post-venetoclax treatments stratified by treatment type [Bruton's tyrosine kinase inhibitor (BTKi), PI3K inhibitor (PI3Ki), and cellular therapies]. RESULTS: We identified patients with CLL who discontinued venetoclax in the first-line (4%) and relapsed/refractory settings (96%). Patients received a median of three therapies prior to venetoclax; 40% were BTKi naïve (n = 130), and 81% were idelalisib naïve (n = 263). ORR to BTKi was 84% (n = 44) in BTKi-naïve patients versus 54% (n = 30) in BTKi-exposed patients. We demonstrate therapy selection following venetoclax requires prior novel agent exposure consideration and discontinuation reasons. CONCLUSIONS: For BTKi-naïve patients, selection of covalently binding BTKis results in high ORR and durable remissions. For BTKi-exposed patients, covalent BTK inhibition is not effective in the setting of BTKi resistance. PI3Kis following venetoclax do not appear to result in durable remissions. We conclude that BTKi in naïve or previously responsive patients and cellular therapies following venetoclax may be the most effective strategies.See related commentary by Rogers, p. 3501.
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Leucemia Linfocítica Crônica de Células B , Compostos Bicíclicos Heterocíclicos com Pontes , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Fosfatidilinositol 3-Quinases , Inibidores de Proteínas Quinases/efeitos adversos , Pirazóis , Pirimidinas , SulfonamidasAssuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/induzido quimicamente , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Pirazóis/efeitos adversos , Pirimidinas/efeitos adversos , Adenina/análogos & derivados , Adulto , Feminino , Humanos , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , PiperidinasRESUMO
Chemotherapy nonspecifically affects all cells undergoing DNA replication and has severe side effects. Understanding of the biology of non-Hodgkin lymphomas has led to development of drugs that target specific lymphoma cell functions and tumor microenvironment. Targeted agents used in combination with chemotherapy pave the way to a chemotherapy-free world. These drugs target multiple oncogenic pathways and modulate the immune system, with better outcomes. Such combinations should be administered only in clinical trials. Incorporating studies of the biology and genetics of these tumors into therapeutic studies may lead to a chemotherapy-free world with improved outcomes and reduced toxicities.
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Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Imunoconjugados/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Humanos , Linfoma não Hodgkin/metabolismo , Linfoma não Hodgkin/patologia , Terapia de Alvo Molecular , Microambiente Tumoral/efeitos dos fármacosRESUMO
Venetoclax (VEN) is approved for relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) as monotherapy (VENmono) or in combination with rituximab. Whether VEN plus anti-CD20 (VENcombo) is superior to VENmono is unknown. We conducted a multicenter, retrospective cohort analysis comparing 321 CLL patients treated with VENmono vs VENcombo across the United States and the United Kingdom. We examined demographics, baseline characteristics, dosing, adverse events, response rates, and outcomes. The primary endpoints were progression-free survival (PFS) and overall survival (OS), estimated by Kaplan-Meier method, in patients treated with VENmono vs VENcombo. Univariate and bivariate analyses were performed with COX regression. Three hundred twenty-one CLL patients were included (3 median prior treatments, 78% prior ibrutinib). The overall response rates (ORRs) were similar (VENmono, 81% ORR, 34% complete remission [CR] vs VENcombo, 84% ORR, 32% CR). With a median follow-up of 13.4 months, no differences in PFS and OS were observed between the groups. In unadjusted analyses, the hazard ratios (HRs) for PFS and OS for VENmono vs VENcombo were HR 1.0 (95% confidence interval [CI], 0.6-1.8; P = .7) and HR 1.2 (95% CI, 0.6-2.3; P = .5), respectively. When adjusting for differences between the cohorts, the addition of an anti-CD20 antibody in combination with VEN did not impact PFS (HR, 1.0; 95% CI, 0.5-2.0; P = .9) or OS (HR, 1.1; 95% CI, 0.4-2.6; P = .8). We demonstrate comparable efficacy between VENmono and VENcombo in a heavily pretreated, high-risk, retrospective cohort, in terms of both response data and survival outcomes. Prospective studies are needed to validate these findings.
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Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Sulfonamidas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/farmacologia , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Retrospectivos , Sulfonamidas/farmacologiaRESUMO
PURPOSE: Clinical trials of venetoclax reported negligible rates of clinical tumor lysis syndrome (TLS) in patients with chronic lymphocytic leukemia (CLL) when using an extended dose escalation schedule. We aimed to understand TLS prophylaxis, rates of select adverse events (AE), and impact of dosing modifications in routine clinical practice. EXPERIMENTAL DESIGN: This retrospective cohort study included 297 CLL venetoclax-treated patients outside of clinical trials in academic and community centers. Demographics, baseline disease characteristics, venetoclax dosing, TLS risk and prophylaxis, and AEs were collected. RESULTS: The group was 69% male, 96% had relapsed/refractory CLL, 45% had deletion chromosome 17p, 84% had unmutated IGHV, 80% received venetoclax monotherapy, and median age was 67. TLS risk was categorized as low (40%), intermediate (32%), or high (28%), and 62% had imaging prior to venetoclax initiation. Clinical TLS occurred in 2.7% of patients and laboratory TLS occurred in 5.7%. Pre-venetoclax TLS risk group and creatinine clearance independently predict TLS development in multivariable analysis. Grade 3/4 AEs included neutropenia (39.6%), thrombocytopenia (29.2%), infection (25%), neutropenic fever (7.9%), and diarrhea (6.9%). Twenty-two patients (7.4%) discontinued venetoclax due to an AE. Progression-free survival was similar regardless of number of dose interruptions, length of dose interruption, and stable venetoclax dose. CONCLUSIONS: These data provide insights into current use of venetoclax in clinical practice, including TLS rates observed in clinical practice. We identified opportunities for improved adherence to TLS risk stratification and prophylaxis, which may improve safety.
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Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Padrões de Prática Médica/normas , Sulfonamidas/uso terapêutico , Síndrome de Lise Tumoral/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/patologia , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The treatment landscape for chronic lymphocytic leukemia (CLL) is rapidly evolving. Targeted agents (TAs) have demonstrated impressive single agent activity and therefore have been replacing chemoimmunotherapy (CIT). Despite their efficacy, the optimal use of the current TAs remains challenging. Perhaps the major dilemma is whether these drugs are best used in sequence or in combinations. Most patients tolerate TA well, notably early during treatment; however, a substantial number discontinue therapy because of toxicities. Therefore, the reasons for discontinuation and, subsequently, the preferred sequence of these agents become critical issues. Although TA monotherapy has revolutionized the treatment of CLL, residual disease, acquired resistance, suboptimal durability of response in patients with high-risk disease, indefinite treatment duration, and decreased compliance over time are issues of concern. To address these challenges, an increasing number of studies are evaluating different combinations of TAs; however, these studies have been mostly small single arm trials in heterogeneous patient populations using different methods for response assessment. A number of questions remain regarding the predictive value of minimal residual disease (MRD) status, durability of response, fixed treatment durations, and importantly, criteria for selection of patients for the optimal combinations. Medical comorbidities, performance status, prior therapies, and disease risk profile are fundamental in determining the treatment plan for each individual patient. Furthermore, utilizing prognostic and predictive markers along with monitoring MRD can guide the development of individualized, better-tolerated, time-limited, and potentially curative chemo-free treatment regimens.
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Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Humanos , Leucemia Linfocítica Crônica de Células B/patologia , PrognósticoRESUMO
INTRODUCTION: Hodgkin's lymphoma (HL) accounts for about 10% of all lymphomas in the U.S.A. Exceptional progress has been made in the treatment of HL with complete response (CR) rates up to 94% in limited stage and 88% in advanced stage disease with regimens such as adriamycin, bleomycin, vinblastine, and dacarbazine in the frontline setting. Nevertheless, up to 10% of patients with limited stage disease and 20-30% of those with advanced stage HL relapse. In the last decade, newer agents such as brentuximab vedotin (BV) and checkpoint inhibitors have been approved by the FDA for treatment of patients with relapsed or refractory HL. As these newer agents are increasingly incorporated in both the frontline and relapsed settings, their optimal sequence becomes challenging for clinicians. Areas covered: This review will discuss the evidence behind the approval of BV and checkpoint inhibitors in HL and the appropriate sequence for using them in relapsed HL. Expert commentary: The appropriate sequence of BV and/or checkpoint inhibitors in the relapsed setting depends on the regimen used in the frontline setting.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Bleomicina/uso terapêutico , Brentuximab Vedotin , Dacarbazina/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Doença de Hodgkin/epidemiologia , Humanos , Imunoconjugados/uso terapêutico , Masculino , Recidiva , Estados Unidos/epidemiologia , Vimblastina/uso terapêuticoRESUMO
INTRODUCTION: Bendamustine, typically in combination with rituximab, is an effective treatment for chronic lymphocytic leukemia (CLL) and B-cell non-Hodgkin lymphoma. Despite its acceptable short-term toxicity profile, long-term toxicities are less well established. This study investigated the long-term adverse effects of bendamustine and responses to subsequent treatments. PATIENTS AND METHODS: Charts of 194 patients were retrospectively reviewed; 54% had received prior treatment (76% attained complete response [CR] or partial response [PR]). RESULTS: Patients who did not achieve a CR or PR did not respond well to subsequent treatments. Malignancies following bendamustine were diagnosed in 11% (21) of patients (first line [7] and salvage [14]), including squamous (8) or basal cell (4) skin cancers; prostate cancer (3), renal cancer (3), bladder cancer (2), melanoma (2), lung cancer (1), and histiocytic sarcoma (1). There were no occurrences of therapy-related myelodysplastic syndrome or acute myelogenous leukemia reported. Infections occurred in 63% of patients; however, no deaths were attributable to bendamustine. CONCLUSION: Bendamustine is an effective therapy with limited long-term sequelae in patients with lymphoid malignancies.
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Antineoplásicos Alquilantes/uso terapêutico , Cloridrato de Bendamustina/uso terapêutico , Leucemia Linfoide/tratamento farmacológico , Linfoma/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cloridrato de Bendamustina/administração & dosagem , Cloridrato de Bendamustina/efeitos adversos , Feminino , Seguimentos , Humanos , Infecções/etiologia , Leucemia Linfoide/complicações , Leucemia Linfoide/diagnóstico , Leucemia Linfoide/mortalidade , Linfoma/complicações , Linfoma/diagnóstico , Linfoma/mortalidade , Masculino , Pessoa de Meia-Idade , Retratamento , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
Although rituximab-based chemoimmunotherapy prolongs the survival of patients with follicular lymphoma (FL), this disease is considered incurable in most patients. Thus, new therapies are needed not only for those in the relapsed/refractory setting, but also for initial treatment. Obinutuzumab (G, GA101) is a third-generation, fully humanized type II glycoengineered, anti-CD20 monoclonal antibody that results in increased direct cell death and antibody-dependent, cell-mediated cytotoxicity/phagocytosis compared to rituximab. Obinutuzumab has significant antitumor activity when used alone or in combinations in untreated or relapsed refractory FL patients. Studies have demonstrated its ability to prolong progression-free survival and, in some cases, overall survival, and to eliminate minimal residual disease. Several ongoing trials are investigating combinations with chemotherapy, immunomodulators, targeted drugs, and immunotherapy agents. G is generally well tolerated, with associated adverse effects including infusion-related reactions, neutropenia, thrombocytopenia, and reactivation of hepatitis B virus. Future studies with this antibody should focus on identifying predictive markers and developing chemotherapy-free combinations that will improve the outcome of patients with FL.
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Although typically indolent in nature, follicular lymphoma remains an ongoing challenge for practicing oncologists. While response rates >90% can be achieved with rituximab-based chemoimmunotherapy in advanced stage patients, the complete remission rates are substantially lower and patients inevitably relapse. The inability to achieve a complete remission and an early progression of disease have recently been determined to be indicative of poorer long-term outcomes. A greater understanding of the pathogenesis of follicular lymphoma has enabled the development of targeted therapies, which may improve standard treatment approaches. Examples include lenalidomide and obinutuzumab, which are currently in front-line Phase III investigation. Other therapies of interest include small molecule inhibitors, immune checkpoint inhibitors and chimeric antigen receptor T cells.
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BACKGROUND: Metallic allergens such as nickel are among the most common causes of allergic contact dermatitis (ACD), but frequencies of contact dermatitis to these allergens may vary in different areas. OBJECTIVES: This study aimed to determine the frequencies of ACD caused by three common metallic allergens: nickel sulfate; potassium dichromate; and cobalt chloride. METHODS: Data for 1137 patients with clinical diagnoses of contact dermatitis and/or atopic dermatitis evaluated by patch testing in Iran during a 5-year period were retrospectively studied to establish the frequencies of hypersensitivity to these metallic allergens. RESULTS: A total of 313 patients (27.5%) gave positive patch test results for at least one metallic allergen. Allergy to nickel (229 cases, 20.0%) was the most commonly observed, followed by allergy to cobalt (90 cases, 8.0%) and allergy to chromium (70 cases, 6.2%). Nickel allergy was significantly more frequent in females and in subjects aged <40 years, whereas chromium hypersensitivity was more common in males and in subjects aged >40 years. Sensitivity to nickel or chromium was a risk factor for cobalt allergy. CONCLUSIONS: Nickel was most commonly identified as a metallic allergen in Iran and tended to affect women aged <40 years. Regulations pertaining to nickel release may decrease the frequency of nickel hypersensitivity in Iran.
Assuntos
Alérgenos/efeitos adversos , Dermatite Alérgica de Contato/epidemiologia , Metais/efeitos adversos , Adolescente , Adulto , Idade de Início , Alérgenos/imunologia , Cobalto/efeitos adversos , Cobalto/imunologia , Dermatite Alérgica de Contato/imunologia , Feminino , Humanos , Irã (Geográfico)/epidemiologia , Modelos Logísticos , Masculino , Metais/imunologia , Níquel/efeitos adversos , Níquel/imunologia , Dicromato de Potássio/efeitos adversos , Dicromato de Potássio/imunologia , Prevalência , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
INTRODUCTION: High frequency ultrasonography (HFUS) is a non-invasive, low risk method which can provide real-time visual information regarding different processes in cutaneous tissue. The goal of this study is to compare the accuracy of HFUS in determining depth and width of basal cell carcinoma (BCC) lesions compared with histopathology as a reference standard. METHODS: The depth and width of 56 primary BCCs in various locations were measured in vivo using the ultrasound system device Digital Taberna Promedica (Luneburg, FRG DUB 20 Ultrasound Scanner), with a 50-MHz hand-held transducer and compared with the depth and width reported in histopathologic examination of these lesions after complete excision. The intraclass correlation coefficient (ICC) was calculated using a one-way ANOVA table to compare measured dimensions for the same tumors with the two diagnostic methods. RESULTS: The mean depth of tumor in HFUS (1353.68 ± 656.456 microns) was lower than the amount measured by the dermatopathologist (1560.71 ± 1044.323 microns). However, the difference was not statistically significant (P > 0.05). The means of largest diameter of tumors in HFUS and pathology were 5996.77 ± 2271.783 and 3891.07 ± 1995.452 microns, respectively (P < 0.001). There was a low correlation in diameter (r = 0.27, P < 0.05) and a moderate correlation in depth (r = 0.45, P < 0.001) of BCCs between these two methods. CONCLUSION: HFUS may be a useful method to assess the dimensions of BCC prior to surgery.
Assuntos
Carcinoma Basocelular/diagnóstico por imagem , Carcinoma Basocelular/patologia , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/patologia , Ultrassonografia/métodos , Ultrassonografia/normas , Adulto , Idoso , Biópsia/normas , Carcinoma Basocelular/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Cuidados Pré-Operatórios/instrumentação , Cuidados Pré-Operatórios/métodos , Cuidados Pré-Operatórios/normas , Padrões de Referência , Reprodutibilidade dos Testes , Neoplasias Cutâneas/cirurgia , Ultrassonografia/instrumentaçãoRESUMO
BACKGROUND: Understanding the physiological, chemical, and biophysical characteristics of the skin helps us to arrange a proper approach to the management of skin diseases. OBJECTIVE: The aim of this study was to measure 6 biophysical characteristics of normal skin (sebum content, hydration, transepidermal water loss (TEWL), erythema index, melanin index, and elasticity) in a normal population and assess the effect of sex, age, and body location on them. METHODS: Fifty healthy volunteers in 5 age groups (5 males and females in each) were enrolled in this study. A multifunctional skin physiology monitor (Courage & Khazaka electronic GmbH, Germany) was used to measure skin sebum content, hydration, TEWL, erythema index, melanin index, and elasticity in 8 different locations of the body. RESULTS: There were significant differences between the hydration, melanin index, and elasticity of different age groups. Regarding the locations, forehead had the highest melanin index, where as palm had the lowest value. The mean values of erythema index and melanin index and TEWL were significantly higher in males and anatomic location was a significant independent factor for all of 6 measured parameters. CONCLUSION: Several biophysical properties of the skin vary among different gender, age groups, and body locations.