RESUMEN
In May 2019, the US Food and Drug Administration (FDA) released the Framework for FDA's Real-World Evidence (RWE) Program, a draft guidance to evaluate the potential use of real-world data in facilitating regulatory decisions. As a result, pharmaceutical companies and medical communities see patient registries, which are large, prospective, noninterventional cohort studies, as becoming increasingly important in providing evidence of treatment effectiveness and safety in clinical practice. Patient registries are designed to collect longitudinal clinical data on a broad population to address critical medical questions over time. With their large sample sizes and broad inclusion criteria, patient registries are often used to generate RWE in the general and underrepresented patient populations that are less likely to be studied in controlled clinical trials. Here, we describe the value of industry-sponsored patient registries in oncology/hematology settings to healthcare stakeholders, in drug development, and in fostering scientific collaboration.
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Industria Farmacéutica , Humanos , Estudios Prospectivos , Resultado del Tratamiento , Sistema de RegistrosRESUMEN
Although new multiple myeloma (MM) therapies are effective in alleviating some disease-associated symptoms (e.g. bone pain, fatigue, functional decline), they can result in additional toxicities, further impacting health-related quality of life (HRQoL). Here, we compared HRQoL and safety of lenalidomide-bortezomib-dexamethasone [RVd (n = 445)], bortezomib-melphalan-prednisone [VMP (n = 77)] and Vd or VMP (n = 588) in patients with newly diagnosed MM (NDMM) from the Connect® MM Registry, a large, USA, multicentre, prospective observational cohort study. Functional Assessment of Cancer Therapy-Multiple Myeloma subscale, EuroQol-5D overall score and Bone Pain Inventory HRQoL scores were significantly improved with RVd versus Vd/VMP. Serious adverse event rates were similar in all groups. Treatment with RVd maintained HRQoL in this real-world, largely community-based population of patients with NDMM.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/psicología , Adulto , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/efectos adversos , Inhibidores de la Angiogénesis/uso terapéutico , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Antineoplásicos Alquilantes/efectos adversos , Antineoplásicos Alquilantes/uso terapéutico , Antineoplásicos Hormonales/efectos adversos , Antineoplásicos Hormonales/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bortezomib/efectos adversos , Bortezomib/uso terapéutico , Estudios de Casos y Controles , Dexametasona/efectos adversos , Dexametasona/uso terapéutico , Femenino , Humanos , Lenalidomida/efectos adversos , Lenalidomida/uso terapéutico , Masculino , Melfalán/efectos adversos , Melfalán/uso terapéutico , Persona de Mediana Edad , Mieloma Múltiple/patología , Prednisona/efectos adversos , Prednisona/uso terapéutico , Estudios Prospectivos , Calidad de Vida/psicología , Sistema de Registros , Seguridad , Trasplante de Células Madre/normasRESUMEN
Median overall survival (OS) has improved for patients with newly diagnosed multiple myeloma (NDMM), but prognosis varies depending on baseline patient characteristics. Current models use data from selected clinical trial populations, which prevent application to patients in an unselected community setting that reflects routine clinical practice. Using data from the Connect® MM Registry, a large, US, multicentre, prospective observational cohort study (Cohort 1: 2009-2011; Cohort 2: 2012-2016) of 3011 patients with NDMM, we identified prognostic variables for OS via the multivariable analysis of baseline patient characteristics in Cohort 1 (n = 1493) and developed a tool to examine individual outcomes. Factors associated with OS (n = 1450 treated patients; P < 0·05) were age, del(17p), triplet therapy use, EQ-5D mobility, International Staging System stage, solitary plasmacytoma, history of diabetes, platelet count, Eastern Cooperative Oncology Group performance status and serum creatinine, which were used to create survival matrices for 3- and 5-year OS. The model was internally and externally validated using Connect MM Cohort 2 (Harrell's concordance index, 0·698), MM-015 (0·649), and the phase 3 FIRST (0·647) clinical trials. This novel prognostic tool may help inform outcomes for NDMM in the era of triplet therapy use with novel agents.
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Mieloma Múltiple/diagnóstico , Mieloma Múltiple/mortalidad , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Deleción Cromosómica , Cromosomas Humanos Par 17 , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/genética , Mieloma Múltiple/patología , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Sistema de Registros , Reproducibilidad de los Resultados , Medición de Riesgo/métodos , Síndrome de Smith-Magenis/mortalidad , Análisis de Supervivencia , Estados Unidos/epidemiología , Adulto JovenRESUMEN
Maintenance therapy after autologous stem cell transplantation (ASCT) is recommended for use in multiple myeloma (MM); however, more data are needed on its impact on health-related quality of life (HRQoL). Presented here is an analysis of HRQoL in a Connect MM registry cohort of patients who received ASCT ± maintenance therapy. The Connect MM Registry is one of the earliest and largest, active, observational, prospective US registry of patients with symptomatic newly diagnosed MM. Patients completed the Functional Assessment of Cancer Therapy-MM (FACT-MM) version 4, EuroQol-5D (EQ-5D) questionnaire, and Brief Pain Inventory (BPI) at study entry and quarterly thereafter until death or study discontinuation. Patients in three groups were analyzed: any maintenance therapy (n = 244), lenalidomide-only maintenance therapy (n = 169), and no maintenance therapy (n = 137); any maintenance and lenalidomide-only maintenance groups were not mutually exclusive. There were no significant differences in change from pre-ASCT baseline between any maintenance (P = 0.60) and lenalidomide-only maintenance (P = 0.72) versus no maintenance for the FACT-MM total score. There were also no significant differences in change from pre-ASCT baseline between any maintenance and lenalidomide-only maintenance versus no maintenance for EQ-5D overall index, BPI, FACT-MM Trial Outcomes Index, and myeloma subscale scores. In all three groups, FACT-MM, EQ-5D Index, and BPI scores improved after ASCT; FACT-MM and BPI scores deteriorated at disease progression. These data suggest that post-ASCT any maintenance or lenalidomide-only maintenance does not negatively impact patients' HRQoL. Additional research is needed to verify these findings.
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Quimioterapia de Mantención , Mieloma Múltiple/tratamiento farmacológico , Calidad de Vida , Sistema de Registros , Talidomida/análogos & derivados , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Lenalidomida , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Talidomida/administración & dosificación , Estados UnidosRESUMEN
Early mortality (EM; death ≤ 6 months from diagnosis) has been reported in several newly diagnosed multiple myeloma (NDMM) trials. Before the era of novel agents, the incidence was 10%-14%. Causes of death included infections/pneumonia, renal failure, refractory disease, and cardiac events. Staging systems, such as the revised International Staging System (r-ISS), and prognostic factors including cytogenetics, lactate dehydrogenase levels, and myeloma-specific factors, are useful to assess overall prognosis; however, they cannot predict EM. We evaluated patients treated with novel agents in the Connect MM® Registry and identified risk factors of the EM cohort. Eligible patients were enrolled in the registry within 60 days of diagnosis. Univariate and multivariate analyses were conducted to evaluate associations between baseline characteristics and EM. Prediction matrices for EM were constructed from a logistic model. Between September 2009 and December 2011, 1493 patients were enrolled in the registry and had adequate follow-up. Of these patients, 102 (6.8%) had EM and 1391 (93.2%) survived for > 180 days. Baseline factors significantly associated with increased EM risk included age > 75 years, higher Eastern Cooperative Oncology Group performance status, lower EQ-5D mobility score, higher ISS stage, lower platelet count, and prior hypertension. Renal insufficiency trended toward increased EM risk. These risk factors were incorporated into a prediction matrix for EM. The EM prediction matrix uses differential weighting of risk factors to calculate EM risk in patients with NDMM. Identifying patients at risk for EM may provide new opportunities to implement patient-specific treatment strategies to improve outcomes.
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Biomarcadores de Tumor/sangre , Mieloma Múltiple , Sistema de Registros , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Hipertensión/sangre , Hipertensión/mortalidad , Hipertensión/fisiopatología , Infecciones/sangre , Infecciones/mortalidad , Infecciones/fisiopatología , L-Lactato Deshidrogenasa/sangre , Masculino , Persona de Mediana Edad , Mieloma Múltiple/sangre , Mieloma Múltiple/mortalidad , Mieloma Múltiple/fisiopatología , Recuento de Plaquetas , Neumonía/sangre , Neumonía/mortalidad , Neumonía/fisiopatología , Tasa de SupervivenciaRESUMEN
BACKGROUND: The t (11;14) (q13;32) translocation [t (11;14)] is present in â¼20% of patients with newly diagnosed multiple myeloma (NDMM), but studies examining its prognostic ability have yielded divergent results, and data are lacking on outcomes from first-line therapy. PATIENTS AND METHODS: Data from the Connect MM Registry, a large US, multicenter, prospective observational cohort study of patients with NDMM were used to examine the effect of t (11;14) status on first-line therapy outcomes in the Overall population (n = 1574) and race groups (African American [AA] vs. non-African American [NAA]). RESULTS: Baseline characteristics were generally similar between patients with (n = 378) and without (n = 1196) t (11;14). Prevalence of t (11;14) was similar by race (AA, 27%; NAA, 24%). In the overall population, regardless of first-line therapy, t (11;14) status did not affect progression-free survival (hazard ratio, 1.02; P = 0.7675) or overall survival (hazard ratio, 0.99; P = .9417). AA patients with t (11;14) had higher likelihood of death (Nominal Cox regression P = .0298) vs. patients without t (11;14). CONCLUSIONS: Acknowledging observational study and inferential limitations, this exploratory analysis of a predominantly community-based population suggests that t (11;14) is a neutral prognostic factor in the general MM population but may be a negative factor for overall survival in AA patients.
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Mieloma Múltiple , Negro o Afroamericano , Humanos , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/genética , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Sistema de Registros , Estudios RetrospectivosRESUMEN
BACKGROUND: The Surveillance, Epidemiology, and End Results (SEER) database and National Cancer Database (NCDB) show improved overall survival (OS) in patients with multiple myeloma (MM) over the last 15 years. This analysis evaluated the validity of the largely community-based Connect MM Registry as a national reference for MM. METHODS: Baseline disease characteristics and survival in US newly diagnosed MM patients were examined using the Connect MM Registry as well as SEER and NCDB databases. Baseline characteristics predictive of longer survival in Connect MM were also identified. RESULTS: As of February 2017, 3011 patients were enrolled in the Connect MM Registry; 2912 were treated. Median age at time of MM diagnosis and age range were numerically similar from 2010 to 2015 across all 3 registries; SEER had a higher representation of nonwhite racial groups than that in the other 2 registries. OS rates suggest proportionate improvement with year of diagnosis among the 3 registries. A Cox proportional hazards model suggests that younger age (<65 years) is associated with longer survival (vs ≥75; HR, 0.39; 95% confidence interval, 0.34-0.46) in the Connect MM Registry. However, sex (HR, 0.91; P = .15) and race (black vs white; HR, 0.88; P = .21) were not associated with longer OS. CONCLUSIONS: Data from the Connect MM Registry appear to be largely representative of national trends, comprehensive, and reliable representations of the national MM population. Baseline characteristics were comparable, and survival similarly improved over time among the 3 registries. CLINICALTRIALS. GOV, IDENTIFIER: NCT01081028.
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Bases de Datos Factuales/estadística & datos numéricos , Mieloma Múltiple/mortalidad , Sistema de Registros/estadística & datos numéricos , Programa de VERF/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Puerto Rico/epidemiología , Reproducibilidad de los Resultados , Tasa de Supervivencia , Estados Unidos/epidemiología , Adulto JovenRESUMEN
PURPOSE: Maintenance therapy after autologous stem cell transplantation (ASCT) improves clinical outcomes in multiple myeloma (MM), but the effect of continued treatment with lenalidomide-only maintenance, or any maintenance, on health care resource utilization (HCRU) is largely unknown. METHODS: Here we present an analysis of HCRU and clinical outcomes in a cohort of patients from the Connect MM registry, the largest, ongoing, observational, prospective US registry of patients with symptomatic newly diagnosed MM. In this study, patients with newly diagnosed MM who completed induction and single ASCT without subsequent consolidation received lenalidomide-only maintenance (nâ¯=â¯180), any maintenance (nâ¯=â¯256), or no maintenance (nâ¯=â¯165). HCRU (hospitalization, surgery/procedures, and concurrent medications [growth factors, bisphosphonates, or neuropathic pain medication]) was assessed starting from 100 days post-ASCT for up to 2 years. FINDINGS: Although the rates of hospitalization per 100 person-years were similar across groups at the end of years 1 and 2, the median duration of hospitalization was numerically longer with no maintenance. The rates of use of growth factors, bisphosphonates, and neuropathic pain medication were generally similar in all 3 groups. The receipt of any maintenance was associated with significantly reduced use of neuropathic pain medications during year 1. Of note, lenalidomide-only maintenance was associated with significantly longer progression-free survival (54.5 vs 30.4 months; hazard ratio [HR]â¯=â¯0.58; 95% CI, 0.43-0.79; Pâ¯=â¯0.0005) and overall survival (OS) (median OS not reached in either group; HRâ¯=â¯0.45; 95% CI, 0.28-0.73; Pâ¯=â¯0.001) compared with no maintenance. Likewise, the group treated with any maintenance had significantly longer median progression-free survival (44.7 vs 30.4 months; HRâ¯=â¯0.62; 95% CI, 0.47-0.82; Pâ¯=â¯0.0008) and OS (median OS not reached in either group; HRâ¯=â¯0.50; 95% CI, 0.33-0.76; Pâ¯=â¯0.001) than did the group that did not receive maintenance. IMPLICATIONS: These findings suggest that in this largely community-based study population, post-ASCT maintenance therapy, including lenalidomide-only maintenance, improves clinical outcomes without negatively affecting HCRU. ClinicalTrials.gov identifier: NCT01081028.
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Trasplante de Células Madre Hematopoyéticas , Factores Inmunológicos/uso terapéutico , Lenalidomida/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Adulto , Anciano , Progresión de la Enfermedad , Femenino , Recursos en Salud , Humanos , Masculino , Persona de Mediana Edad , Sistema de Registros , Trasplante Autólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
Autologous stem cell transplantation (ASCT) followed by lenalidomide maintenance therapy is the standard of care for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). Clinical trials show progression-free survival (PFS) benefits, with some studies (Cancer and Leukemia Group [CALGB] trial and meta-analysis) also showing overall survival (OS) benefits, but applicability to real-world clinical settings is unclear. Using data from Connect MM, the largest US-based observational registry of NDMM patients, we analyzed effects of maintenance therapy on long-term outcomes in 1450 treated patients enrolled from 2009 to 2011. Patients who received induction therapy and ASCT (n = 432) were analyzed from 100 days post-ASCT (data cut 7 January 2016): 267 received maintenance (80% lenalidomide-based [of whom 88% received lenalidomide monotherapy]); 165 did not. Lenalidomide maintenance improved median PFS and 3-year PFS rate vs no maintenance (50.3 vs 30.8 months [hazard ratio (HR), 0.62; 95% confidence interval (CI), 0.46-0.82; P < .001] and 56% vs 42%, respectively). Improvements in median OS and 3-year OS rate were associated with lenalidomide maintenance vs no maintenance (not reached in either group [HR, 0.54; 95% CI, 0.36-0.83; P = .005] and 85% vs 70%, respectively). Five hematologic serious adverse events were reported with lenalidomide maintenance (pancytopenia [n = 2], febrile neutropenia, anemia, and thrombocytopenia [n = 1 each]) and 1 with no maintenance (thrombocytopenia). Second primary malignancies occurred at rates of 1.38 and 2.19 events per patient-year in lenalidomide maintenance and no maintenance groups, respectively. Survival benefits associated with lenalidomide maintenance previously demonstrated in clinical trials were observed in this community-based Connect MM Registry.
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Trasplante de Células Madre Hematopoyéticas , Quimioterapia de Mantención , Mieloma Múltiple/mortalidad , Mieloma Múltiple/terapia , Sistema de Registros , Adulto , Anciano , Aloinjertos , Ensayos Clínicos como Asunto , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Factores de TiempoRESUMEN
BACKGROUND: The treatment landscape for multiple myeloma (MM) has undergone recent changes with the regulatory approval of several new therapies indicated for second- and later-line disease. Using data from Connect MM, the largest multisite, primarily community-based, prospective, observational registry of MM patients in the United States, selection of second-line treatments was evaluated during a 5-year period from 2010 to 2016. PATIENTS AND METHODS: Eligible patients were aged ≥ 18 years, had newly diagnosed MM ≤ 2 months before study entry, and were followed for up to 8 years. Patients who received ≥ 2 lines of therapy were analyzed. "Tepee" plots of stacked area graphs differentiated treatments by color to allow visualization of second-line treatment trends in MM patients. RESULTS: As of February 2017, 855 of 2897 treated patients had progressed to second-line treatment. Treatment selection was heterogeneous; shifting patterns of treatment choices coincided with the approval status of newer agents. The most common treatment regimens in the early part of the decade were lenalidomide and/or bortezomib, with or without dexamethasone, with increasing use of newer agents (carfilzomib, pomalidomide, daratumumab, and elotuzumab) and triplet combinations over time. The influence of the baseline patient characteristics of age, history of diabetes, peripheral neuropathy, and renal function on treatment choice was also examined. CONCLUSION: These findings indicate that community physicians are current in their MM management practices, with uptake of new drugs and acquaintance with results of randomized clinical trials using combinations almost concurrent with their regulatory approval and publication.
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Mieloma Múltiple/epidemiología , Mieloma Múltiple/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Manejo de la Enfermedad , Historia del Siglo XXI , Humanos , Mieloma Múltiple/historia , Pronóstico , Vigilancia en Salud Pública , Retratamiento , Análisis de Supervivencia , Resultado del Tratamiento , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: The performance of multiple myeloma (MM) therapies in a general patient population and specific eligibility criteria that might limit enrollment into randomized controlled trials (RCTs) have not been evaluated in depth. This study aimed to determine if improvements seen with MM therapies in RCTs are reflected in the general patient population and to identify eligibility criteria that can be modified to increase enrollment. PATIENTS AND METHODS: The Connect MM Registry is a prospective observational cohort study of patients with newly diagnosed MM (NDMM) in the United States. Using common RCT exclusion criteria collected from 16 published studies, patients in the registry were categorized according to their eligibility for inclusion in RCTs. RESULTS: On the basis of common criteria, 563 of 1406 of registry patients (40.0%) are ineligible for RCTs. Criteria leading to exclusion included M-protein ≤ 1.0 g/dL (25.2%), creatinine > 2.5 mg/dL (13.9%), low absolute neutrophil count (10.0%), and low hemoglobin (9.6%). Significantly more RCT-ineligible versus RCT-eligible patients had hypercalcemia (11.0% vs. 5.5%), elevated creatinine levels (38.9% vs. 6.2%), low hemoglobin levels (59.5% vs. 39.5%), or International Staging System stage III disease (40.1% vs. 22.1%; P < .001 for all comparisons). RCT-ineligible patients had a lower 3-year survival rate than RCT-eligible patients (63% vs. 70%). The incidence of serious adverse events was similar between groups. CONCLUSION: Of patients with NDMM enrolled in the Connect MM Registry, 40% are ineligible for RCTs. This study provides insight into potential modifications of standard eligibility criteria that can lead to improved RCT design and accelerated enrollment.
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Mieloma Múltiple/epidemiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Proyectos de Investigación , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores , Femenino , Adhesión a Directriz , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/mortalidad , Mieloma Múltiple/terapia , Estadificación de Neoplasias , Sistema de Registros , Resultado del Tratamiento , Adulto JovenAsunto(s)
Factores Inmunológicos/administración & dosificación , Mieloma Múltiple , Inhibidores de Proteasoma/administración & dosificación , Sistema de Registros , Trasplante de Células Madre , Anciano , Aloinjertos , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/mortalidad , Mieloma Múltiple/terapia , Tasa de SupervivenciaRESUMEN
This study examines alcohol use, transactional sex (TS), and sexually transmitted infection (STI) risk among sugar plantation residents near Moshi, Tanzania, from 2002 to 2004. We compare popular discourse gathered through ethnographic methods with cross-sectional questionnaire and STI prevalence data to illuminate the close correspondence of alcohol use and TS with STI transmission. People attributed to alcohol varied consequences: some socially desirable (relaxing, reducing worries) and others (drunkenness, removing shame) thought to put alcohol abusers at risk for STIs. TS-exchanging money, food, gifts, alcohol or work for sex-was not stigmatized, but people believed that seeking sexual partners for money (or providing money to sexual partners) led to riskier sexual relationships. We explore popular discourse about how alcohol use and TS independently and in combination led to increased STI exposure. Popular discourse blamed structural circumstances-limited economic opportunities, few social activities, separated families-for risky sex and STIs. To understand individual behavior and risk, we surveyed 556 people. We measured associations between their self-reported behaviors and infection with herpes simplex virus type-2 (HSV-2), syphilis, and HIV in 462 participants who were tested. Alcohol abuse was associated with prevalent STI and HIV infection. Exchanging sex for alcohol and work were both associated with prevalent STI. Participants who both abused alcohol and participated in TS had greatest risk for STI. Findings from the two analytic methods-interrogation of popular discourse, and association between self-reported behavior and STIs-were largely in agreement. We posit explanations for discrepancies we found through the concepts of sensationalization, self-exceptionalization, and the influence of an authoritative moral discourse.