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BACKGROUND: Obesity is an established modifiable risk factor for multiple myeloma (MM). However, associations of obesity and MM risk in Black populations, for whom obesity and MM are more common, is less clear. METHODS: Using participants enrolled in the Integrative Molecular And Genetic Epidemiology study, we evaluated the association of anthropometric traits with MM risk overall, stratified by race and sex. Among cases, we assessed the association of BMI with the presence of myeloma-defining events. RESULTS: We observed an 18% increase in MM risk for every 5 kg/m2 increase in usual adult BMI. Participants with severe obesity (BMI ≥ 40 kg/m2) had the highest risk compared to those with a normal usual adult BMI (18.5-24.9 kg/m2; OR = 1.87, 95% CI 1.25-2.80), particularly among Black men (OR = 3.94, 95% CI 0.90-17.36). Furthermore, MM cases with overweight/obesity (BMI ≥ 25 kg/m2) were more likely to present at diagnosis with low renal function (OR = 1.62, 95% CI 1.09-2.40), deletion 13q (OR = 1.73, 95% CI 1.08-2.76) and lytic lesions or compression fractures (OR = 2.39, 95% CI 0.82-7.01) and less likely to present with severe diffuse osteopenia (OR = 0.51, 95% CI 0.31-0.81). CONCLUSIONS: Findings underscore the importance of obesity as a modifiable risk factor for MM, particularly in high-risk populations, and for the clinical presentation of disease.
Assuntos
Índice de Massa Corporal , Mieloma Múltiplo , Obesidade , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antropometria , Negro ou Afro-Americano/estatística & dados numéricos , Mieloma Múltiplo/epidemiologia , Mieloma Múltiplo/genética , Obesidade/complicações , Obesidade/epidemiologia , Fatores de Risco , Fatores Sexuais , BrancosRESUMO
The combination of anti-CD38 monoclonal antibodies to a proteasome inhibitor, an immunomodulatory agent and dexamethasone (quadruplet-QUAD) in sequence with autologous stem cell transplantation (ASCT) leads to deep and durable responses in newly diagnosed multiple myeloma (NDMM). Disease progression in the first year post-QUADs is uncommon. We analysed 274 consecutive NDMM patients treated with QUADs + ASCT. After a median follow-up of 21.3 months, 20 patients had disease progression <18 months and 21 had progression ≥18 months after the onset of a QUAD regimen. All patients received subsequent anti-MM therapy, and 38 were evaluated for response. Nine (22.0%) received T-cell redirecting therapy as the next treatment, and 21 (51.2%) at some point in the treatment course. Response to next therapy was 26.3% for patients with progression <18 months and 52.6% for those with progression ≥18 months after the onset of a QUAD regimen. Median PFS on the next therapy was 2.5 months (95% CI 1.5-3.4) for those with progression <18 months and 7.0 months (95% CI 3.6-10.5) for those with progression ≥18 months. Efforts should focus on the early deployment of therapies with new mechanism of action for patients experiencing treatment failure after QUADs.
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Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/terapia , Mieloma Múltiplo/tratamento farmacológico , Bortezomib/uso terapêutico , Transplante Autólogo , Progressão da Doença , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Dexametasona/uso terapêuticoRESUMO
Bispecific T cell engagers (TCE) derive from monoclonal antibodies and concomitantly engage a target on the surface of cancer cell and CD3 on the surface of T-cells. TCEs promote T cell activation and lysis of tumor cells. Most TCEs in development for multiple myeloma (MM) target the B cell maturation antigen (BCMA) and differ among themselves in structure, pharmacokinetics, route and schedule of administration. CD3/BCMA TCEs produce response in ~60% of patients treated in phase 1 trials. TCEs are also in development targeting the G protein-coupled receptor, class C group 5 member D (GPRC5D) and the Fc receptor homologue 5 (FcRH5). Main toxicities are cytokine release syndrome and cytopenias. Here we review the current development and future directions of TCEs in MM.
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Anticorpos Biespecíficos , Mieloma Múltiplo , Humanos , Linfócitos T , Anticorpos Biespecíficos/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Antígeno de Maturação de Linfócitos B , Anticorpos MonoclonaisRESUMO
It is not known whether obesity has a differential effect on allogeneic haematopoietic cell transplantation outcomes with alternative donor types. We report the results of a retrospective registry study examining the effect of obesity [body mass index (BMI) > 30] on outcomes with alternative donors (haploidentical related donor with two or more mismatches and receiving post-transplant cyclophosphamide [haplo] and cord blood (CBU)] versus matched unrelated donor (MUD). Adult patients receiving haematopoietic cell transplantation for haematologic malignancy (2013-2017) (N = 16 182) using MUD (n = 11 801), haplo (n = 2894) and CBU (n = 1487) were included. The primary outcome was non-relapse mortality (NRM). The analysis demonstrated a significant, non-linear interaction between pretransplant BMI and the three donor groups for NRM: NRM risk was significantly higher with CBU compared to haplo at BMI 25-30 [hazard ratio (HR) 1.66-1.71, p < 0.05] and MUD transplants at a BMI of 25-45 (HR, 1.61-3.47, p < 0.05). The results demonstrated that NRM and survival outcomes are worse in overweight and obese transplant recipients (BMI ≥ 25) with one alternative donor type over MUD, although obesity does not appear to confer a uniform differential mortality risk with one donor type over the other. BMI may serve as a criterion for selecting a donor among the three (MUD, haplo and CBU) options, if matched sibling donor is not available.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Adulto , Índice de Massa Corporal , Seleção do Doador , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Recidiva Local de Neoplasia , Obesidade , Estudos Retrospectivos , Doadores não RelacionadosRESUMO
Clinical practice guidelines recommend protamine sulfate for reversal of enoxaparin associated bleeds dependent on the time from last administration and dose of enoxaparin. We present a case of a hemodynamically unstable patient with an enoxaparin induced abdominal wall hematoma/hemorrhage and the previous enoxaparin administration 21.5â¯h prior to presentation with a therapeutic anti-Xa assay (0.8â¯IU/mL) upon assessment in the emergency department. Along with resuscitative efforts, an interdisciplinary team collaborated to administer protamine sulfate 50â¯mg intravenous once (0.5â¯mg per 1â¯mg of enoxaparin) to reverse the therapeutic anticoagulation. Our case demonstrates the importance of monitoring renal function and the potential for accumulation of enoxaparin in patients with renal dysfunction leading to prolonged therapeutic anti-Xa assays. With the availability of anti-Xa assays, future reversal recommendations of enoxaparin associated bleeds using protamine sulfate should include the initial anti-Xa assay as a guide for the dosing regimen.
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Anticoagulantes/efeitos adversos , Enoxaparina/efeitos adversos , Hematoma/induzido quimicamente , Hematoma/tratamento farmacológico , Antagonistas de Heparina/uso terapêutico , Protaminas/uso terapêutico , Parede Abdominal/diagnóstico por imagem , Idoso , Esquema de Medicação , Serviço Hospitalar de Emergência , Feminino , Hematoma/complicações , Hematoma/diagnóstico por imagem , Humanos , Insuficiência Renal Crônica/complicações , Fatores de Tempo , Tomografia Computadorizada por Raios XRESUMO
Increasing number of older adults with Plasma Cell Disorders (PCDs) are receiving autologous stem cell transplant (ASCT) in the US. Hospital associated disability (HAD) is a common complication associated with acute care hospitalization among older adults. To estimate the prevalence and prognostic significance of HAD among older adults with MM undergoing ASCT. This retrospective cohort study used consecutive adults ≥ 18 y with PCD receiving ASCT at a single institution between 1/2013 and 5/2023. Trained nursing staff assessed Katz Activities of Daily Living (ADL) at admission and every 3 days thereafter under our Virtual Acute Care for Elders program. The primary outcome was development of HAD defined as ≥1 point decline on the Katz Activities of Daily Living (ADL) scale from hospital admission to discharge. We examined the association between putative risk factors such as age, Karnofsky performance status (KPS), baseline ADL score, Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) and HAD using modified Poisson regression models with robust variance estimators. Subsequently, we studied the impact of HAD on downstream adverse events including 30-day readmission rates and long term survival. We included 778 adults with a median age of 62 y (QR 56-68 y), with 56% males and 55% non-Hispanic Whites. In the overall population, 112 (14.4%) developed HAD, with much higher incidence among older adults ≥ 65 y compared to those <65 y at ASCT (22% vs. 9%, P value < .01). In multivariable analysis, increasing age (RR 1.56; 95% CI 1.25-1.94, per 10 y increase), female sex (RR 1.79; 95% CI 1.27-2.53) and KPS ≤ 70 (RR 2.55; 95% CI 1.32-4.94) were associated with an increased risk of developing HAD. As compared to those without, patients with HAD had a two-fold higher risk of 30-day readmission (95% CI 1.16-3.39) and a 3.7-fold increased risk of all-cause mortality (95% CI 2.15-6.22). Nearly one in 4 older adults ≥ 65 y developed HAD while undergoing ASCT which was associated with a two-fold increased risk of 30-day readmission. Interventions to prevent HAD and its downstream consequences are critically needed.
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INTRODUCTION: Health outcome preferences of older adults with cancer vary based on burden/intensity of treatment and its impact on health outcomes such as survival, quality of life, and functional and cognitive well-being. We studied the association between age and health outcome preferences of adults with multiple myeloma (MM). MATERIALS AND METHODS: Using a single center prospective cohort study, we identified adults ≥50y with MM who underwent geriatric assessment (GA) within 30 days of initiating a new line of therapy. We assessed health outcome preferences using a nine-item health outcome preference scale where patients were asked to prioritize varying treatment outcomes in a Likert scale. We compared the response patterns for each item by age group (50-69y vs ≥70y) using Mantel-Haenszel chi-squared test. For items significant in bi-variable analysis, we built proportional odds models to study the association between age and health outcome preferences adjusting for sex, race, frailty, and high risk cytogenetics. RESULTS: We included 119 patients with a median age of 65y. Of these, 58% were male, 56% were non-Hispanic White, and 28% were frail. Older adults (≥70y) versus younger adults (50-69y) were more likely to prioritize health outcomes such as quality of life (53% vs. 34%), functional independence (74% vs. 33%), maintaining cognitive ability (79% vs. 54%), and living free from pain (50% vs 18%) over longer survival (all p values <0.05). In multivariable models, each one interquartile range (IQR) increase in age was associated with increased odds of prioritization of functional independence [adjusted odds ratio (aOR) 2.55, 95% confidence interval (CI) (1.44-4.53)], maintaining cognitive ability [aOR 1.75, 95% CI (1.01-3.02)], and willingness to take milder/ fewer treatments [aOR 2.40, 95% CI (1.36-4.26)] over longer survival. Similarly, each IQR increase in age was associated with decreased odds of prioritization of survival over quality of life [aOR 0.45, 95% CI (0.26-0.78)] and survival over being free from pain [aOR 0.39, 95% CI (0.22-0.69)]. DISCUSSION: Three out of four older adults (age ≥ 70y) with MM rated other outcomes, particularly functional and cognitive well-being, above survival. Determining the most significant treatment outcomes for older adults with MM can aid in establishing treatment goals and enhance shared decision-making.
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Avaliação Geriátrica , Mieloma Múltiplo , Preferência do Paciente , Qualidade de Vida , Humanos , Mieloma Múltiplo/psicologia , Mieloma Múltiplo/terapia , Mieloma Múltiplo/mortalidade , Masculino , Idoso , Feminino , Estudos Prospectivos , Pessoa de Meia-Idade , Avaliação Geriátrica/métodos , Idoso de 80 Anos ou mais , Fatores EtáriosRESUMO
Waldenström Macroglobulinemia (WM) is a unique, low grade, IgM lymphoplasmacytic lymphoma with a heterogeneous clinical course. A paucity of high-grade evidence from large phase 3 trials remains a major issue in the field despite a rapidly expanding therapeutic armamentarium against WM. Prior knowledge of the patients' MYD88L265P and CXCR4 mutation status aids in treatment decision making if Bruton's tyrosine kinase (BTK) inhibitor therapy is being considered. Head-to head comparative data to inform optimal approach are lacking, and a particularly vexing issue for the clinicians is choosing between fixed-duration bendamustine-rituximab (BR) therapy and an indefinite BTK inhibitor-based regimen, given that both approaches are well tolerated and effective, particularly for the patient population harboring MYD88L265P mutation. For the patients with MYD88WT genotype, chemo-immunotherapy such as BR is preferred, although zanubrutinib, a potent second generation BTK inhibitor, with its reduced off target effects and greater BTK occupancy compared to its predecessor, ibrutinib, has also recently shown activity in MYD88WT WM. This review summarizes the current literature pertaining to the diagnosis, prognosis, and the treatment of WM.
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Macroglobulinemia de Waldenstrom , Humanos , Terapia de Alvo Molecular , Mutação , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , Rituximab/uso terapêutico , Macroglobulinemia de Waldenstrom/diagnóstico , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Macroglobulinemia de Waldenstrom/genéticaRESUMO
Allogeneic hematopoietic cell transplant (HCT) is a curative therapy for malignant and non-malignant blood diseases. Drug use may be associated with adverse outcomes. We performed a retrospective analysis to assess non-relapse mortality (NRM) and overall survival (OS) in HCT patients with drug use. The medical charts of 232 patients were reviewed. Recipients of matched unrelated donor (MUD) or matched related donor (MRD) transplants were included. Drug use was defined by either metabolic evidence or provider documentation prior to transplant. Transplants were MUD (n = 148) or MRD (n = 84). Median follow-up duration was 15.5 months. There were 35 (15%) patients in the drug use group and 197 (85%) patients in the control group; 49% and 60.4% were in remission at the time of transplant, respectively. In univariate analysis, drug use was associated with a 3-year cumulative incidence of NRM of 43% vs 29% for the control group (p = 0.048), and an HR of 1.75, (95% CI: 1.02-2.99). After controlling for age, sex, disease status, and graft type, drug use was associated with a hazard ratio (HR) of 1.6 (95% CI: 0.95-2.92) for NRM, and an HR 1.2 (95% CI: 0.74-1.94) for OS. Larger cohorts may be needed to further evaluate this association.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Preparações Farmacêuticas , Humanos , Estudos Retrospectivos , Doadores de Tecidos , TransplantadosRESUMO
Patients undergoing hematopoietic cell transplantation (HCT) experience decline in their physical activity during their transplant admission. There is limited experience with prospective monitoring of transplant recipients. We therefore measured physical activity and sleep patterns of subjects undergoing autologous and allogeneic HCT. Eighty-three patients were consented for this study. Sixty-three patients competed the study and had their physical activity prospectively assessed using the fitness-tracking device Fitbit HR. Outcomes included adherence, physical activity, readmission, hematopoietic engraftment, and 100-day survival. Sixty percent of patients (n = 37) underwent autologous HCT, and 40% (n = 26) underwent allogenic HCT. Both groups had a comparable number of steps at admission to the hospital. The number of daily steps during the study period was lower in the allogeneic group (2159 versus 3008, P = .07), as was the minimum number of steps recorded over the transplant admission (allogeneic HCT = 395 versus autologous HCT = 848, P = .01). Patients undergoing allogeneic HCT were less active on the day before discharge (1956 steps versus 3183 steps, P = .08). In multivariate analysis, physical activity was not associated with HCT-related outcomes. Patients undergoing HCT experience significant decline in their physical activity during their transplant admission that does not recover by the time of discharge. This effect can be objectively measured using fitness tracking devices.