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PURPOSE: To conduct an independent assessment of inter- and intraobserver agreement for the META score as a tool for differentiating osteoporotic vertebral fractures and multiple myeloma vertebral fractures. METHODS: This is a retrospective observational study. The magnetic resonance imaging analysis was made by two independent spinal surgeons. We designated a Subjective assessment, in which the surgeon should establish a diagnostic classification for each vertebral fracture based on personal experience: secondary to osteoporosis, categorized as a benign vertebral fracture (BVF), or attributed to multiple myeloma, categorized a malign vertebral fracture (MVF). After a 90-day interval, both surgeons repeated the evaluations. For the next step, the observers should establish a diagnosis between BVF and MVF according to the META score system, and both observers repeated the evaluations after a 90-day interval. The intra and interobserver reliability of the Subjective evaluation was studied using the kappa (κ) test. Then, the META evaluations were paralleled using the intraclass correlation coefficient (ICC). RESULTS: A total of 220 patients who had the potential to participate in the study were initially enrolled, but after applying the exclusion criteria, 44 patients were included. Thirty-three patients had BVF, and 12 patients presented MVF. Interobserver agreement for both Subjective evaluations moments (initial and 90-days interval) found a slight agreement for both moments (0.35 and 0.40 respectively). Kappa test for both META evaluations moments (initial and 90-days interval) found a moderate interobserver agreement for both moments (0.54 and 0.48 respectively). It was observed that the ICC calculated for the Initial evaluation using META score was 0.680 and that in the 90-days interval was 0.726, indicating regular to good agreement. Kappa test for intraobserver agreements for the Subjective evaluation presented moderate agreement for both Surgeons. On the other side, Kappa test for intraobserver agreements for the META evaluation presented substantial agreement for both Surgeons. The Intraclass Correlation Coefficient of the META score found presented an almost perfect agreement for both Surgeons. CONCLUSION: Intra and interobserver agreement for both surgeons were unsatisfactory. The lack of consistent reproducibility by the same observer discourages and disfavors the routine use of the META score in clinical decision making, when potentially cases of multiple myeloma may be present.
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Mieloma Múltiplo , Variações Dependentes do Observador , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Humanos , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/etiologia , Idoso , Feminino , Fraturas por Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/diagnóstico , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Diagnóstico Diferencial , Idoso de 80 Anos ou mais , Imageamento por Ressonância Magnética , Reprodutibilidade dos TestesRESUMO
INTRODUCTION: Fatigue is prevalent across a wide range of medical conditions and can be debilitating and distressing. It is likely that fatigue is experienced differently according to the underlying aetiology, but this is poorly understood. Digital health technologies present a promising approach to give new insights into fatigue.The aim of this study is to use digital health technologies, real-time self-reports and qualitative interview data to investigate how fatigue is experienced over time in participants with myeloma, long COVID, heart failure and in controls without problematic fatigue. Objectives are to understand which sensed parameters add value to the characterisation of fatigue and to determine whether study processes are feasible, acceptable and scalable. METHODS AND ANALYSIS: An ecological momentary assessment study will be carried out over 2 or 4 weeks (participant defined). Individuals with fatigue relating to myeloma (n=10), heart failure (n=10), long COVID (n=10) and controls without problematic fatigue or a study condition (n=10) will be recruited. ECG patches will measure heart rate variability, respiratory rate, body temperature, activity and posture. A wearable bracelet accompanied by environment beacons will measure physical activity, sleep and room location within the home. Self-reports of mental and physical fatigue will be collected via smartphone app four times daily and on-demand. Validated fatigue and affect questionnaires will be completed at baseline and at 2 weeks. End-of-study interviews will investigate experiences of fatigue and study participation. A feedback session will be offered to participants to discuss their data.Data will be analysed using multilevel modelling and machine learning. Interviews and feedback sessions will be analysed using content or thematic analyses. ETHICS AND DISSEMINATION: This study was approved by the East of England-Cambridge East Research Ethics Committee (22/EE/0261). The results will be disseminated in peer-reviewed journals and at international conferences. TRIAL REGISTRATION NUMBER: NCT05622669.
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COVID-19 , Avaliação Momentânea Ecológica , Fadiga , Humanos , Fadiga/etiologia , Insuficiência Cardíaca/fisiopatologia , Tecnologia Digital , Mieloma Múltiplo/complicações , SARS-CoV-2 , Autorrelato , Projetos de Pesquisa , Dispositivos Eletrônicos VestíveisRESUMO
PURPOSE: Financial toxicity is a contributor to the psychosocial burden of cancer care. There is no consensus measure of financial toxicity; however, recent studies have adopted the Comprehensive Score for Financial Toxicity (COST). Despite its growing popularity, data on the responsiveness to change of the COST instrument are lacking. To address this gap in the literature, we performed a sequential mixed-methods study of people with multiple myeloma. MATERIALS AND METHODS: In the quantitative phase of the study, we collected COST scores at two time points approximately 8 weeks apart from 72 patients. In the qualitative phase, we conducted semistructured interviews with a subset of 12 patients who reported the largest changes in scores. The qualitative data were analyzed using a deductive coding scheme developed using the Framework Method in the context of a commonly cited conceptual model of financial toxicity. RESULTS: The median absolute change in COST scores was four points (IQR, 2-6). Only 13% of the sample had the same COST scores at both assessments; 38% had an improved score and 50% had a worsened score. Only, seven of the 12 patients (58%) interviewed reported changes to one or more of the constructs in the conceptual model of financial toxicity. Most commonly, changes to out-of-pocket medical costs were reported (5/12). Changes to nonmedical expenses (n = 2) and subjective financial distress without changes to objective financial burden (n = 2) were also reported. CONCLUSION: Additional research is needed to explicate changes in COST scores over time.
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Mieloma Múltiplo , Humanos , Mieloma Múltiplo/economia , Mieloma Múltiplo/terapia , Mieloma Múltiplo/complicações , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Efeitos Psicossociais da DoençaRESUMO
AIM: To study the dynamics of calculated indices [neutrophil-lymphocyte ratio (NLR); systemic inflammation index (SIV)] and biomarkers of systemic inflammation [interleukin-1ß (IL-1ß); high-sensitivity C-reactive protein (hsCRP)], parameters of the structure-and-function state of the myocardium and intracardiac hemodynamics, and their relationship in patients newly diagnosed with multiple myeloma (MM) at the onset of the disease and after 6 courses of chemotherapy (CT) containing the proteasome inhibitor bortezomib. MATERIAL AND METHODS: This prospective study included 30 patients aged 63.8±10.0 years diagnosed with MM; 17 (56.7 %) of them were men. The following tests were performed for all patients: measurement of IL-1ß and hsCRP, calculation of the inflammation indexes NLR and SIV, transthoracic echocardiography before and after 6 courses of bortezomib-containing CT. At the time of study completion, 9 patients dropped out due to reasons not related to cardiovascular complications of CT. RESULTS: The antitumor therapy was associated with increases of immune-inflammation indexes: NLR increased from 1.54 [1.02; 1.83] to 2.9 [1.9; 4.35] (p=0.009) and SIV increased from 402.95 [230.5; 534.0] to 1102.2 [453.1; 1307.9] (Ñ=0.014). IL-1ß increased from 5.15 [4.05; 5.77] to 6.22 [5.66; 6.52]âpg/ml remaining within the reference range (p=0.142) whereas hsCRP decreased from 1.02 [0.02; 2.71] to 0.02 [0.02; 0.82]âIU/l (p=0.138). Statistically significant changes in parameters of heart remodeling and clinical picture of cardiovascular complications were not observed. A correlation analysis showed significant inverse correlations of hsCRP with left ventricular ejection fraction (LV EF) (r= -0.557; p=0.003), the number of plasma cells (PC) with LV EF (r= -0.443; p=0.023), and a direct correlation of the number of PC with hsCRP (r=0.433; p=0.022). CONCLUSION: During the study, the accepted criteria for cardiotoxicity of bortezomib-containing chemotherapy in patients with MM, were not met. The identified correlations between the level of markers for acute inflammation, indexes of intracardiac hemodynamics, and the immediate MM substrate may indicate the role of chronic low-intensity inflammation in the pathogenesis of myocardial remodeling in patients with MM. This necessitates further studies on larger samples of patients to assess the prognostic significance.
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Mieloma Múltiplo , Masculino , Humanos , Feminino , Bortezomib/efeitos adversos , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Proteína C-Reativa/metabolismo , Volume Sistólico , Estudos Prospectivos , Função Ventricular Esquerda , Miocárdio , InflamaçãoRESUMO
Multiple myeloma (MM) is associated with an increased risk of venous and arterial thrombosis. Pathophysiologic mechanisms include patient, disease and treatment related factors. Risk assessment models have been developed to determine whichpatients are at highest thrombotic risk and pursuant to this, risk adapted thrombosis prophylaxis has been suggested. Areas in which further basic and clinical research is imperative include the molecular and cellular mechanisms of thrombosis in myeloma, the inclusion of relevant biomarkers in risk assessment scores and controlled clinical trials of VTE prophylaxis and treatment using direct oral anticoagulants.
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Mieloma Múltiplo , Trombose , Tromboembolia Venosa , Humanos , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/terapia , Anticoagulantes/efeitos adversos , Medição de Risco , Trombose/prevenção & controle , Trombose/complicações , Fatores de RiscoRESUMO
Objective: To compare the predictive efficacy of the two thrombosis risk assessment scores (Padua and IMPEDE scores) in venous thromboembolism (VTE) within 6 months in patients with newly diagnosed multiple myeloma (NDMM) in China. Methods: This study reviewed the clinical data of 421 patients with NDMM hospitalized in Beijing Jishuitan Hospital from April 2014 to February 2022. The sensitivity, specificity, accuracy, and Youden index of the two scores were calculated to quantify the thrombus risk assessment of VTE by the Padua and IMPEDE scores. The receiver operating characteristics curves of the two evaluation scores were drawn. Results: The incidence of VTE was 14.73%. The sensitivity, specificity, accuracy, and Youden index of the Padua score were 100%, 0%, 14.7%, and 0% and that of the IMPEDE score was 79%, 44%, 49.2%, and 23%, respectively. The areas under the curve of Padua and IMPEDE risk assessment scores were 0.591 and 0.722, respectively. Conclusion: IMPEDE score is suitable for predicting VTE within 6 months in patients with NDMM.
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Mieloma Múltiplo , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/etiologia , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Medição de Risco , Fatores de Risco , Curva ROC , Estudos RetrospectivosRESUMO
Venous thromboembolism (VTE) is among the complications of Multiple Myeloma (MM) and may occur in up to 10% of this patient population. However, medications used in MM therapy such as immunomodulators (IMID) may raise these rates. Thus, risk prediction models have been developed to quantify the risk of VTE in MM patients. The aim of this study is to compare the performance of three risk assessment models for VTE in newly diagnosed MM (NDMM) patients using immunomodulatory agents. A historical cohort study during a 10-year period in a Brazilian metropolis with NDMM treated with IMID. Data were collected from patient's medical charts for the period of one year to calculate the scores using IMPEDE VTE, SAVED, and International Myeloma Working Group (IMWG) guidelines. The area under the curve (AUC) of the Receiver Operating Characteristic curve analysis was calculated to assess the discriminative power of three risk assessment models. We included 131 patients (9 in the VTE group versus 122 in the non VTE group). According to IMPEDE, 19.1, 62.6, and 18.3% of patients were considered low, intermediate, and high risk, respectively. SAVED classified 32.1% as high risk and 64.9% had ≥2 risk factors based on IMWG guidelines. The AUC of the IMPEDE VTE score was 0.80 (95% CI 0.66-0.95, p = 0.002), of the SAVED score was 0.69 (95% CI 0.49-0.89, p = 0.057), and of the IMWG risk score was 0.68 (95% CI 0.48-0.88, p = 0.075). IMPEDE VTE was the most accurate in predicting the development of VTE in Brazilian patients on IMID therapy. The SAVED score and the IMWG guidelines did not show discriminative ability in predicting VTE based on the population involved in this study.
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Mieloma Múltiplo , Tromboembolia Venosa , Humanos , Mieloma Múltiplo/complicações , Mieloma Múltiplo/tratamento farmacológico , Anticoagulantes/uso terapêutico , Estudos de Coortes , Brasil/epidemiologia , Medição de Risco , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Fatores de Risco , Fatores Imunológicos/uso terapêutico , Estudos RetrospectivosRESUMO
BACKGROUND: Teclistamab, a B-cell maturation antigen × CD3 bispecific antibody, demonstrated an overall response rate of 63.0% in 165 heavily pretreated patients with relapsed or refractory multiple myeloma in the phase 1/2 MajesTEC-1 study. Cytokine release syndrome (CRS), a known manifestation of T-cell redirection, was observed in 119 of 165 patients (72.1%). METHODS: Patients received once-weekly teclistamab 1.5 mg/kg subcutaneously after two step-up doses (0.06 and 0.3 mg/kg). CRS was graded according to American Society for Transplantation and Cellular Therapy criteria and managed according to the study protocol, including use of tocilizumab and/or steroids. RESULTS: Most cases of CRS occurred during the step-up dosing schedule of teclistamab and were grade 1 (50.3% of patients) or grade 2 (21.2% of patients); a single case of grade 3 CRS was reported in a patient with concurrent grade 3 pneumonia. All CRS cases resolved and none led to treatment discontinuation. Overall, 33.3% of patients had >1 CRS event; CRS recurrence was reduced when tocilizumab was administered for the first CRS event compared with when it was not (20.0% vs. 62.2%, respectively). Baseline characteristics such as tumor burden and cytokine levels did not appear to predict CRS incidence or severity. CONCLUSIONS: Findings of this study support the need for preemptive planning and prompt management of CRS in patients treated with T-cell-engaging bispecific antibodies. Intervention with tocilizumab for CRS appears to decrease the likelihood of patients experiencing subsequent CRS events without compromising response to teclistamab. PLAIN LANGUAGE SUMMARY: Cytokine release syndrome (CRS), observed in 72.1% of patients treated with teclistamab in the MajesTEC-1 study, was mostly grade 1 or 2 and manageable, without requiring treatment discontinuation. Most CRS occurred during the step-up schedule, requiring vigilance during treatment initiation. Ensure fever is resolved and patients have no signs of infection before initiating the teclistamab step-up schedule or administering the next teclistamab dose, to avoid exacerbating CRS. Tocilizumab reduced the risk of subsequent CRS in patients receiving it for their first CRS event (20.0% vs. 62.2% in those not receiving it), without affecting response to teclistamab. No baseline characteristics, including tumor burden or cytokine levels, appeared to clearly predict for CRS occurrence or severity.
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Anticorpos Biespecíficos , Antineoplásicos , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/complicações , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/etiologia , Anticorpos Biespecíficos/efeitos adversos , Incidência , Antineoplásicos/uso terapêutico , CitocinasRESUMO
Monoclonal immunoglobulin deposition disease (MIDD), often associated with plasma cell dyscrasias, predominantly affects the kidneys. In this disease, hematologic response (HR) to treatment can be reliably assessed by International Myeloma Working Group (IMWG) consensus criteria, while uniform criteria for assessing renal response are lacking. We report a retrospective analysis of renal outcomes among 34 patients with MIDD. With most patients treated with bortezomib and autologous stem cell transplantation, 26 of 28 (94%) achieved very good partial HR or better. We demonstrate that both IMWG (based on estimated glomerular filtration rate, eGFR) and amyloid (based on proteinuria) criteria are needed to capture renal response: among 28 evaluable patients, 6 (21%) had isolated proteinuria, while 13 (46%) had isolated decreased eGFR. Using both criteria, which were concordant in patients with both decreased eGFR and proteinuria, 22 of 28 patients (79%) achieved a renal response, including 2 of 7 discontinuing dialyses. All 6 patients (100%) with isolated proteinuria and 7 of 13 (54%) with isolated decreased eGFR achieved renal response, suggesting that isolated proteinuria is an early manifestation of MIDD associated with reversible renal damage. Baseline eGFR predicted renal response (p = .02 by quartile) and survival (p = .02), while HR (CR vs. non-CR) did not, probably because of high HR rate. With a median follow-up of 110 months, the median overall survival was 136 months (95% CI: 79-NR) and median renal survival had not been reached. Prospective studies using uniform renal response criteria are needed to optimize the management of MIDD.
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Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/complicações , Mieloma Múltiplo/tratamento farmacológico , Estudos Retrospectivos , Consenso , Estudos Prospectivos , Transplante Autólogo , Rim , Proteinúria/etiologia , ImunoglobulinasRESUMO
OBJECTIVE: To examine the risk of hematologic malignancies in older adults with ankylosing spondylitis (AS). PATIENTS AND METHODS: We used US Medicare data from January 1, 1999, to December 31, 2010, to identify a population-based cohort of beneficiaries with AS. We also included beneficiaries with inflammatory bowel disease (IBD) as disease controls and beneficiaries without AS or IBD as unaffected controls. We excluded those treated with tumor necrosis factor inhibitors in this period. We followed up each group for new diagnosis claims for hematologic malignancies until September 30, 2015. RESULTS: We included 12,451 beneficiaries with AS, 234,905 with IBD, and 10,975,340 unaffected controls, with a mean follow-up of 9.9, 9.3, and 8.0 years, respectively. We identified 297 hematologic malignancies in the AS group, 4538 malignancies in the IBD group, and 128,239 malignancies in unaffected controls. The standardized incidence ratio in AS vs unaffected controls was 1.39 (95% CI, 1.05 to 1.61) for non-Hodgkin lymphoma, 1.50 (95% CI, 1.17 to 1.92) for chronic lymphocytic leukemia, and 1.52 (95% CI, 1.12 to 2.06) for multiple myeloma. Risks of acute myeloid leukemia and chronic myeloid leukemia were not elevated in AS, and there were too few cases of Hodgkin lymphoma to compute risks. Risks were comparable to those of beneficiaries with IBD. We also performed a systematic literature review of the risk of hematologic malignancy in AS, focusing on age associations, which have not been previously examined. We identified 21 studies in the systematic literature review, which included mainly young or middle-aged patients. Results suggested that AS was largely not associated with an increased risk of hematologic malignancies. Two cohort studies reported an increased risk of multiple myeloma in AS. CONCLUSION: The risks of non-Hodgkin lymphoma, chronic lymphocytic leukemia, and multiple myeloma are increased among elderly patients with AS.
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Neoplasias Hematológicas , Doenças Inflamatórias Intestinais , Leucemia Linfocítica Crônica de Células B , Linfoma não Hodgkin , Mieloma Múltiplo , Espondilite Anquilosante , Pessoa de Meia-Idade , Humanos , Idoso , Estados Unidos/epidemiologia , Mieloma Múltiplo/complicações , Estudos de Coortes , Leucemia Linfocítica Crônica de Células B/epidemiologia , Leucemia Linfocítica Crônica de Células B/complicações , Espondilite Anquilosante/complicações , Espondilite Anquilosante/tratamento farmacológico , Espondilite Anquilosante/epidemiologia , Medicare , Neoplasias Hematológicas/complicações , Linfoma não Hodgkin/epidemiologia , Linfoma não Hodgkin/etiologia , Linfoma não Hodgkin/patologia , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/epidemiologiaRESUMO
PURPOSE: Increased use of oral anticancer agents (OAAs) has empowered adults with multiple myeloma (MM) to manage their oncolytic therapy, but such a shift may result in issues with medication use, particularly among patients being concurrently treated for pre-existing, multiple chronic conditions. METHODS: This retrospective cohort study used 2013-2018 commercial and Medicare claims data to assess medication use in adults with MM. To be included, adults (18 years and older) must have been diagnosed with and had 2+ claims for an OAA, had continuous enrollment for 12 months before and after OAA initiation, and have been previously diagnosed with and had prescription fills for 2+ select chronic conditions. The proportion of days covered metric assessed medication adherence and was compared for 12 months before and after the OAA initiation by Wilcoxon signed-rank tests, McNemar's tests, and difference-in-differences models. RESULTS: The mean OAA adherence in the first year of therapy was 58.3% (standard deviation: 24.5) and 65.1% (standard deviation: 27.01) for commercial and Medicare patients, respectively. Adherence and the proportion adherent (proportion of days covered ≥ 80%) to comorbid therapies generally declined in the first year after OAA initiation. Changes in medication use were particularly noticeable among those on antihypertensive therapy: adjusted analyses uncovered a 2.5% (Medicare) and 5.2% (commercial) difference in adherence to these medications between those initially adherent and nonadherent to OAA therapy (both P < .05). CONCLUSION: Initiating OAA therapy in adults with MM may complicate an already complex treatment regimen, resulting in poor overall medication adherence in patients with multiple comorbid conditions.
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Antineoplásicos , Mieloma Múltiplo , Adulto , Idoso , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Doença Crônica , Humanos , Medicare , Adesão à Medicação , Mieloma Múltiplo/complicações , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/epidemiologia , Estudos Retrospectivos , Estados Unidos/epidemiologiaRESUMO
Background: Minimal residual disease (MRD) is an important prognostic factor for evaluating a deeper treatment response in patients with multiple myeloma (MM). We evaluated the clinical utility of next-generation flow (NGF)-based MRD assessment in a heterogeneous MM patient population. Methods: Patients with suspected morphological remission after or during MM treatment were prospectively enrolled. In total, 108 bone marrow samples from 90 patients were analyzed using NGF-based MRD assessment according to the EuroFlow protocol, and progression-free survival (PFS) was evaluated according to the International Myeloma Working Group response status, cytogenetic risk, and MRD status. Results: The overall MRD-positive rate was 31.5% (34/108 samples), and MRD-positive patients showed a lower PFS than MRD-negative patients (P=0.005). MRD-positive patients showed inferior PFS than MRD-negative in patients with stringent complete remission (sCR)/complete remission (P=0.014) and high-risk cytogenetic abnormalities (P=0.016). MRD was assessed twice in 18 patients with a median interval of 12 months. Sustained MRD negativity was only observed in patients with sustained sCR, and their PFS was superior to that of patients who were not MRD-negative (P=0.035). Conclusions: Clinical application of NGF-based MRD assessment can provide valuable information for predicting disease progression in patients with MM in remission, including those with high-risk cytogenetic abnormalities.
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Mieloma Múltiplo , Humanos , Aberrações Cromossômicas , Citometria de Fluxo , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Neoplasia Residual/diagnósticoRESUMO
Arrhythmias are a major cardiac complication reported among patients with multiple myeloma (MM), but these have not been further characterized in this population. We explored the prevalence of arrhythmias and examined the predictors of mortality among patients with MM with arrhythmias. The National Inpatient Sample data collected between 2016 and 2018 were used to conduct retrospective analyses. Multivariable logistic regression analyses were done to examine the predictors of mortality among patients with MM with arrhythmias. 16.9% of patients with MM reported a diagnosis of any arrhythmias and 70.7% of these were atrial fibrillation. Patients aged 70 years and above had 21% lower odds (adjusted OR (AOR): 0.79; 95% CI: 0.68 to 0.92) of inpatient mortality relative to younger patients. Those in the non-Hispanic black, Hispanic, and non-Hispanic other category were 1.38 (95% CI: 1.16 to 1.64), 1.53 (95% CI: 1.19 to 1.97), and 1.69 (95% CI: 1.29 to 2.21) times more likely to die during hospitalization compared with their counterparts who were non-Hispanic whites. Relative to patients with MM who were on Medicare, those on private (AOR: 1.28; 95% CI: 1.06 to 1.54) and other insurance types (AOR: 1.78; 95% CI: 1.23 to 2.58) had higher odds of mortality. Other predictors of inpatient mortality were elective admission (AOR: 0.67; 95% CI: 0.52 to 0.85) and Charlson comorbidity indices between 5-7 (AOR: 1.23; 95% CI: 1.07 to 1.41) and ≥8 (AOR: 1.45; 95% CI: 1.21 to 1.73) compared with comorbidity indices between 0 and 4. Our study adds to the body of knowledge on the need for proper diagnosis and management of cardiac arrhythmias in patients with MM. Research is needed to further assess the time of arrhythmia diagnosis and its impact on health outcomes among patients with MM.
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Fibrilação Atrial , Mieloma Múltiplo , Idoso , Fibrilação Atrial/complicações , Hospitalização , Humanos , Medicare , Mieloma Múltiplo/complicações , Estudos Retrospectivos , Estados Unidos/epidemiologiaRESUMO
Chimeric antigen receptor (CAR) T-cell therapies are highly effective for multiple myeloma (MM) but their impressive efficacy is associated with treatment-related neurotoxicities in some patients. In CARTITUDE-1, 5% of patients with MM reported movement and neurocognitive treatment-emergent adverse events (MNTs) with ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen-targeted CAR T-cell therapy. We assessed the associated factors for MNTs in CARTITUDE-1. Based on common features, patients who experienced MNTs were characterized by the presence of a combination of at least two variables: high tumor burden, grade ≥2 cytokine release syndrome (CRS) or any grade immune effector cell-associated neurotoxicity syndrome (ICANS) after cilta-cel infusion, and high CAR T-cell expansion/persistence. Strategies were implemented across the cilta-cel development program to monitor and manage patients with MNTs, including enhanced bridging therapy to reduce baseline tumor burden, early aggressive treatment of CRS and ICANS, handwriting assessments for early symptom detection, and extended monitoring/reporting time for neurotoxicity beyond 100 days post-infusion. After successful implementation of these strategies, the incidence of MNTs was reduced from 5% to <1% across the cilta-cel program, supporting its favorable benefit-risk profile for treatment of MM.
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Mieloma Múltiplo , Síndromes Neurotóxicas , Receptores de Antígenos Quiméricos , Humanos , Imunoterapia Adotiva/efeitos adversos , Incidência , Mieloma Múltiplo/complicações , Mieloma Múltiplo/terapia , Síndromes Neurotóxicas/etiologia , Receptores de Antígenos Quiméricos/uso terapêuticoRESUMO
OBJECTIVES: Findings from a brief geriatric assessment (GA) in a cohort of adults with multiple myeloma (MM) are presented, with particular attention to the utility of the GA in identifying important deficits in adults judged to have a normal Karnofsky Performance Status (KPS ≥ 80). MATERIALS AND METHODS: Adults age 18 and older with MM were recruited into an observational study from 2018 to 2020. A modified Cancer and Aging Research Group (CARG) GA was administered at enrollment. Enrollees also completed the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life of Cancer Patients Core 30 questionnaire (QLQ-C30), with subscales of physical, social, role, and cognitive functioning (range 0-100; higher values indicate better function). Data were analyzed using descriptive statistics for the full cohort and stratified by concurrent KPS (score < 80 vs ≥ 80). RESULTS: Among 89 adults, the mean age was 69.1 years, 68% were aged ≥65 years, and 70% were white. In this cohort, 78% had KPS ≥ 80. Among those with KPS ≥ 80, functional impairments (Timed Up and Go ≥14 s and dependence in ≥1 instrumental activity of daily living) were seen in 30% and 21%, respectively, with 11% reporting ≥1 fall in the prior 6 months. At least two GA-identified deficits were detected in 50% of the overall cohort and in 41% of those with KPS ≥ 80. Among those with KPS ≥ 80, self-reported physical impairment on EORTC QLQ-C30 was noted by 34%. CONCLUSION: Using a modified CARG GA and EORTC questionnaire, functional impairments were identified among adults considered to have a good performance status based on a KPS (≥ 80). Future studies should focus on using GA measures for therapy assignment and identifying opportunities for intervening upon GA-identified deficits.
Assuntos
Avaliação Geriátrica , Mieloma Múltiplo , Idoso , Humanos , Avaliação de Estado de Karnofsky , Mieloma Múltiplo/complicações , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
BACKGROUND. The recently released Myeloma Response Assessment and Diagnosis System (MY-RADS) for multiple myeloma (MM) evaluation using whole-body MRI (WB-MRI) describes the total burden score. However, assessment is confounded by red bone marrow hyperplasia in anemia. OBJECTIVE. The purpose of this study is to assess the utility of the MY-RADS total burden score, ADC, and fat fraction (FF) from WB-MRI in predicting early treatment response in patients with newly diagnosed MM and to compare the utility of these measures between patients with and without anemia. METHODS. This retrospective study included 56 patients (40 men, 16 women; mean age, 57.4 ± 9.6 [SD] years) with newly diagnosed MM who underwent baseline WB-MRI including DWI and modified Dixon sequences. Two radiologists recorded total burden score using MY-RADS and measured the ADC and FF of diffuse and focal disease sites. Mean values across sites were derived. Interobserver agreement was evaluated, and the mean assessments of the readers were used for further analyses. Presence of deep response after four cycles of induction chemotherapy was recorded. Patients were classified as having anemia if their hemoglobin level was less than 100 g/L. The utility of WBMRI parameters in predicting deep response was assessed. RESULTS. A total of 24 of 56 patients showed deep response, and 25 of 56 patients had anemia. Interobserver agreement, which was expressed using intraclass correlation coefficients, ranged from 0.95 to 0.99. Among patients without anemia, those with deep response compared with those without deep response had a lower total burden score (9.0 vs 18.0), a lower ADC (0.79 × 10-3 mm2/s vs 1.08 × 10-3 mm2/s), and a higher FF (0.21 vs 0.10) (all p < .001). The combination of these three parameters (optimal cutoffs: ≤ 15 for total burden score, ≤ 0.84 × 10-3 mm2/s for ADC, and > 0.16 for FF) achieved sensitivity of 93.8%, specificity of 93.3%, and accuracy of 93.5% for predicting deep response. In patients with anemia, none of the three parameters were significantly different between patients with and without deep response (all p > .05), and the combination of parameters achieved sensitivity of 56.3%, specificity of 100.0%, and accuracy of 72.0%. CONCLUSION. Low total burden score, low ADC, and high FF from WB-MRI may predict deep response in patients with MM, although only among those without anemia. CLINICAL IMPACT. WB-MRI findings may help guide determination of prognosis and initial treatment selection in MM.
Assuntos
Anemia/complicações , Imageamento por Ressonância Magnética/métodos , Mieloma Múltiplo/diagnóstico por imagem , Mieloma Múltiplo/patologia , Sistemas de Informação em Radiologia , Imagem Corporal Total/métodos , Tecido Adiposo/diagnóstico por imagem , Efeitos Psicossociais da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Valor Preditivo dos Testes , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Diffusion-weighted whole-body MRI (DW-MRI) is increasingly used in the management of multiple myeloma (MM) patients, but data regarding the prognostic role of DW-MRI imaging response after treatment are lacking. The Myeloma Response Assessment and Diagnosis System (MY-RADS) imaging recommendations recently proposed the criteria for response assessment category (RAC) with a 5-point scale in order to standardize response assessment after therapy, but this score still needs to be validated. METHODS: We investigated the prognostic role of RAC criteria in 64 newly diagnosed MM patients after autologous stem cell transplantation (ASCT), and we combined the results of MY-RADS with those of minimal residual disease (MRD) assessment by multiparametric flow cytometry (MFC). RESULTS: Superior post-ASCT PFS and OS were observed in patients with complete imaging response (RAC1), with respect to patients with imaging residual disease (RAC≥2): median PFS not reached (NR) versus 26.5 months, p = 0.0047, HR 0.28 (95% CI: 0.12-0.68); 3-year post-ASCT OS 92% versus 69% for RAC1 versus RAC ≥2, respectively, p = 0.047, HR 0.24 (95% CI: 0.06-0.99). Combining MRD and imaging improved prediction of outcome, with double-negative and double-positive features defining groups with excellent and dismal PFS, respectively (PFS NR vs. 10.6 months); p = 0.001, HR 0.07 (95%CI: 0.01-0.36). CONCLUSION: The present study supports the applicability of MY-RADS recommendations after ASCT; RAC criteria were able to independently stratify patients and to better predict their prognosis and the combined use of DW-MRI with MFC allowed a more precise evaluation of MRD.
Assuntos
Citometria de Fluxo/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/complicações , Mieloma Múltiplo/terapia , Neoplasia Residual/diagnóstico , Condicionamento Pré-Transplante/métodos , Transplante Autólogo/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasia Residual/patologia , PrognósticoRESUMO
In this review, two types of soft-tissue involvement in multiple myeloma are defined: (i) extramedullary (EMD) with haematogenous spread involving only soft tissues and (ii) paraskeletal (PS) with tumour masses arising from skeletal lesions. The incidence of EMD and PS plasmacytomas at diagnosis ranges from 1·7% to 4·5% and 7% to 34·4% respectively. EMD disease is often associated with high-risk cytogenetics, resistance to therapy and worse prognosis than in PS involvement. In patients with PS involvement a proteasome inhibitor-based regimen may be the best option followed by autologous stem cell transplantation (ASCT) in transplant eligible patients. In patients with EMD disease who are not eligible for ASCT, a proteasome inhibitor-based regimen such as lenalidomide-bortezomib-dexamethasone (RVD) may be the best option, while for those eligible for high-dose therapy a myeloma/lymphoma-like regimen such as bortezomib, thalidomide and dexamethasone (VTD)-RVD/cisplatin, doxorubicin, cyclophosphamide and etoposide (PACE) followed by SCT should be considered. In both EMD and PS disease at relapse many strategies have been tried, but this remains a high-unmet need population.
Assuntos
Mieloma Múltiplo/terapia , Plasmocitoma/terapia , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/uso terapêutico , Cisplatino/uso terapêutico , Ciclofosfamida/uso terapêutico , Dexametasona/uso terapêutico , Gerenciamento Clínico , Doxorrubicina/uso terapêutico , Etoposídeo/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Humanos , Lenalidomida/uso terapêutico , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/patologia , Plasmocitoma/complicações , Plasmocitoma/diagnóstico , Plasmocitoma/patologia , Prognóstico , Transplante AutólogoRESUMO
BACKGROUND: Chronic kidney disease (CKD) is common in patients with multiple myeloma (MM) and is associated with a poor prognosis. We assessed CKD-associated clinical outcomes among elderly patients with MM initiating chemotherapy in the United States. MATERIALS AND METHODS: We identified elderly Medicare beneficiaries (≥66 years) diagnosed with MM who initiated first-line therapy from 2008 to 2014. We identified CKD using diagnosis codes. We followed patients for death, time to next treatment (TTNT), and myeloma-defining events (anemia, hypercalcemia, skeletal-related events, progression to/of CKD) until September 30, 2015. We estimated overall survival, TTNT, and cumulative incidence of myeloma-defining events using the Kaplan-Meier method and risk of CKD-associated outcomes using Cox proportional hazards models, adjusting for demographics and comorbid conditions. RESULTS: Of 22,484 included patients, 8704 (39%) had CKD at first-line therapy initiation. Compared with patients without CKD, patients with CKD had shorter median overall survival (2.1 vs. 3.6 years) and median TTNT (10.0 vs. 12.4, 9.7 vs. 11.2, 8.3 vs. 9.2, and 6.9 vs. 8.3 months at first- to fourth-line therapy). Probability of CKD progression for patients at stages 1 to 5 was higher than the probability of developing CKD for patients without CKD (3-year cumulative incidence [95% confidence interval, CI], 47% [45-48%] vs. 27% [24-26%]). Adjusted hazard ratios for CKD versus non-CKD were: all-cause death, 1.23 (95% CI, 1.18-1.28); anemia, 1.34 (95% CI, 1.24-1.45); hypercalcemia, 1.23 (95% CI, 1.09-1.38); skeletal-related events, 0.85 (95% CI, 0.90-0.91); and TTNT, from 1.03 (95% CI, 0.96-1.10) at third-line therapy to 1.15 (95% CI, 1.04-1.27) at fourth-line therapy. CONCLUSION: Data from the study suggest that CKD-associated clinical burden is substantial in elderly patients with MM.