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1.
Blood ; 140(23): 2443-2450, 2022 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-35772005

RESUMO

Although venous thromboembolism (VTE) is an important treatment and disease-related complication in myeloma, a validated risk prediction model including disease-specific variables such as cytogenetics or tumor burden is lacking. The aim of this study was to develop a new risk prediction model for VTE in the context of modern antimyeloma therapy. All consecutive patients diagnosed at the Cleveland Clinic between 2008 and 2018 and with available data on baseline candidate risk factors constituted the derivation cohort. The primary outcome was VTE (deep venous thrombosis/pulmonary embolism) within 1 year of treatment initiation. A multivariable model was used, and weights were derived from subdistribution hazard ratios to construct a risk score. The model was validated both by internal bootstrap validation and in an external validation cohort. The derivation cohort consisted of 783 patients. A 5-component risk prediction tool, named the PRISM score, was developed, including the following variables: prior VTE, prior surgery, immunomodulatory drug use, abnormal metaphase cytogenetics, and Black race. The c-statistic of the model was 0.622 (95% confidence interval [CI], 0.567-0.674). The model stratified patients into low, intermediate, and high risk, with 12-month cumulative VTE incidence of 2.7%, 10.8%, and 36.5%, respectively. Risk of VTE increased significantly with increasing score in both the derivation and the external validation data sets, with a subdistribution hazard ratio per 1-point increase of 1.28 (95% CI, 1.19-1.39; P < .001) and 1.23 (95% CI, 1.07-1.41; P = .004) respectively. Although the PRISM score can guide clinicians in identifying patients at a high risk of VTE, additional external validation is necessary for incorporation into routine clinical practice.


Assuntos
Tromboembolia Venosa , Humanos , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/genética , Citogenética
2.
Am J Hematol ; 99(6): 1205-1207, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38602288

RESUMO

The findings of this study highlight a 95% accuracy rate in ChatGPT responses, as assessed by five myeloma specialists, underscoring its potential as a reliable educational tool.


Assuntos
Mieloma Múltiplo , Educação de Pacientes como Assunto , Mieloma Múltiplo/terapia , Mieloma Múltiplo/diagnóstico , Humanos , Masculino , Feminino
3.
Br J Haematol ; 193(6): 1213-1219, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33997961

RESUMO

The IMPEDE VTE score has recently emerged as a novel risk prediction tool for venous thromboembolism (VTE) in multiple myeloma (MM). We retrospectively reviewed 839 patients with newly diagnosed MM between 2010 and 2015 at Cleveland Clinic and included 575 patients in final analysis to validate this score. The c-statistic of the IMPEDE VTE score to predict VTE within 6 months of treatment start was 0·68 (95% CI: 0·61-0·75). The 6-month cumulative incidence of VTE was 5·0% (95% CI: 2·1-7·9) in the low risk group, compared to 12·6% (95% CI: 8·9-16·4%) and 24·1% (95% CI: 12·2-36·1) in the intermediate and high risk groups (P < 0·001 for both). In addition, a higher proportion of patients in the VTE cohort had ECOG performance status of ≥2 as compared to the no VTE cohort (33% vs. 16%, P = 0·001). Other MM characteristics such as stage, immunoglobulin subtype, and cytogenetics were not predictors of VTE. In summary, we have validated the IMPEDE VTE score in our patient cohort and our findings suggest that it can be utilized as a VTE risk stratification tool in prospective studies looking into investigating VTE prophylaxis strategies in MM patients.


Assuntos
Mieloma Múltiplo/sangue , Mieloma Múltiplo/epidemiologia , Tromboembolia Venosa/sangue , Tromboembolia Venosa/epidemiologia , Idoso , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/terapia , Estudos Retrospectivos , Fatores de Risco , Tromboembolia Venosa/prevenção & controle
4.
Br J Haematol ; 189(6): 1074-1082, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32108328

RESUMO

Characterisation and prognostic impact of immunoparesis in relapsed multiple myeloma (MM) is lacking in the current literature. We evaluated 258 patients with relapsed MM, diagnosed from 2008 to 2015, to investigate the prognostic impact of deep immunoparesis on post-relapse survival. On qualitative immunoparesis assessment, no, partial and full immunoparesis was present in 9%, 30% and 61% of patients, respectively. Quantitative immunoparesis was assessed by computing the average relative difference (ARD) between polyclonal immunoglobulin(s) and corresponding lower normal limit(s), with greater negative values indicating deeper immunoparesis. The median ARD was -39%, with an optimal cut-off of -50% for overall survival (OS) by recursive partitioning analysis. Deep immunoparesis (ARD ≤-50%) was associated with a higher tumour burden at first relapse compared to none/shallow [ARD >-50%] immunoparesis. The OS (P = 0·007) and progression-free survival (PFS; P < 0·001) differed significantly between the deep and none/shallow immunoparesis groups. Kaplan-Meier estimates for 3-year OS were 36% and 46%, and for 2-year PFS were 17% and 27%, respectively. On multivariable analysis (MVA) for PFS, both qualitative and quantitative immunoparesis retained negative prognostic impact independently. However, only quantitative immunoparesis was independently prognostic for OS on MVA. Depth of immunoparesis in relapsed MM is an important prognostic factor for post-relapse survival in the era of novel agents and continuous therapy.


Assuntos
Doenças do Sistema Imunitário , Mieloma Múltiplo , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Doenças do Sistema Imunitário/etiologia , Doenças do Sistema Imunitário/imunologia , Doenças do Sistema Imunitário/mortalidade , Doenças do Sistema Imunitário/patologia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/terapia , Estudos Retrospectivos , Taxa de Sobrevida
5.
Am J Hematol ; 94(4): 439-445, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30663805

RESUMO

Response rate and survival in multiple myeloma (MM) has improved in the era of proteasome inhibitors and immunomodulatory drugs. However, most patients eventually relapse with biochemical progression (BP) alone or with clinical features of end-organ damage (CP: clinical progression), without or without extramedullary (EM) disease. We conducted a retrospective cohort study of 252 patients with MM experiencing first relapse (time, T0 ) to evaluate survival following CP with and without EM as a function of BP. Patients were divided into three groups: BP (n = 134; 53%), CP/EM- (n = 87; 35%) and CP/EM+ (n = 31; 12%). The median time from diagnosis to T0 was significantly shorter in CP/EM+ compared to CP/EM- and BP groups (13 vs 25 vs 25 months; P < 0.001). The incidence of abnormal metaphase cytogenetics at diagnosis was significantly higher in CP/EM+ compared to CP/EM- and BP groups (46% vs 18% vs 11% respectively; P < 0.001). At a median follow-up of 26 months from T0 , median overall survival was 50, 19 and 10 months for BP, CP/EM- and CP/EM+ groups, respectively (P < 0.001). On multivariable analysis, pattern of progression was a significant prognostic factor for OS (HR for CP/EM- vs BP: 3.6; CP/EM+ vs BP: 8.7 and CP/EM+ vs CP/EM-: 2.42; P < 0.001 for all comparisons), along with age at T0 . In conclusion, progression pattern is an important prognostic factor in the current era, with subsequent survival being dismal in patients with end-organ damage or EM disease at relapse. Clinical trials in relapsed MM should consider reporting patterns of progression at baseline to ensure balance between study arms.


Assuntos
Bases de Dados Factuais , Mieloma Múltiplo , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/genética , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/terapia , Recidiva , Taxa de Sobrevida
8.
Am J Hematol ; 89(4): 349-54, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24273135

RESUMO

A previous interim report of MM-011, the first study that combined lenalidomide with anthracycline-based chemotherapy followed by lenalidomide maintenance for relapsed and/or refractory multiple myeloma (RRMM), showed promising safety and activity. We report the long-term outcomes of all 76 treated patients with follow-up ≥ 5 years. This single-center phase I/II study administered lenalidomide (10 mg on days 1-21 of every 28-day cycle), intravenous liposomal doxorubicin (40 mg/m(2) on day 1), dexamethasone (40 mg on days 1-4), and intravenous vincristine (2 mg on day 1). After 4-6 planned induction cycles, lenalidomide maintenance therapy was given at the last tolerated dose until progression, with or without 50 mg prednisone every other day. The median number of previous therapies was 3 (range, 1-7); 49 (64.5%) patients had refractory disease. Forty-three (56.6%) patients received maintenance therapy. Grade 3/4 adverse events occurred during induction and maintenance therapy in 48.7% and 25.6% of patients, respectively. Four (5.3%) treatment-related deaths occurred during induction. Responses were seen in 53.0% (at least partial response) and 71.2% (at least minor response) of patients. Overall, median progression-free survival and overall survival were 10.5 and 19.0 months, respectively; in patients with refractory disease these values were 7.5 and 11.3 months, respectively. Lenalidomide with anthracycline-based chemotherapy followed by maintenance lenalidomide provided durable control in patients with RRMM (ClinicalTrials.gov number, NCT00091624).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Terapia de Salvação , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Terapia Combinada , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Resistencia a Medicamentos Antineoplásicos , Feminino , Seguimentos , Doenças Hematológicas/induzido quimicamente , Humanos , Controle de Infecções , Estimativa de Kaplan-Meier , Cariotipagem , Lenalidomida , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/genética , Mieloma Múltiplo/terapia , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Modelos de Riscos Proporcionais , Indução de Remissão , Talidomida/administração & dosagem , Talidomida/efeitos adversos , Talidomida/análogos & derivados , Trombose/prevenção & controle , Resultado do Tratamento , Vincristina/administração & dosagem , Vincristina/efeitos adversos
9.
Blood Cancer J ; 14(1): 90, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38821914

RESUMO

The presence of extramedullary disease (EMD) has been associated with poor outcomes in patients with relapsed-refractory multiple myeloma (RRMM). Herein, we report the outcomes of RRMM patients who were treated with standard-of-care (SOC) chimeric antigen receptor (CAR) T-cell therapy and had active extraosseous EMD before the infusion. Data were retrospectively collected from patients at three US institutions with the intent to receive SOC CAR T. Responses were assessed per the International Myeloma Working Group criteria. A total of 152 patients proceeded with infusion, of whom 47 (31%) had EMD (EMD group) and 105 (69%) did not (non-EMD group). Baseline patient characteristics were comparable between the two groups. The EMD group had a higher incidence of high-grade CRS, steroid and anakinra use, and thrombocytopenia on day +30 compared to the non-EMD group. In addition, the EMD group had an inferior overall response rate (58% vs 96%, p < 0.00001), median progression-free survival (PFS) (5.1 vs 12.4 months; p < 0.0001), and overall survival (OS) (12.2 vs 27.5 months; p = 0.00058) compared to the non-EMD group. We further subdivided the non-EMD patients into those with paramedullary disease (PMD-only group, n = 26 [17%]) and those with neither EMD nor PMD (bone marrow-contained group or BM-only group, n = 79 [52%]). Patients with PMD-only had similar median PFS (11.2 vs 13.6 months, p = 0.3798) and OS (not reached [NR] vs 27.5 months, p = 0.6446) compared to patients with BM-only disease. However, patients with EMD exhibited inferior median PFS (5.1 vs 13.6 months, p < 0.0001) and OS (12.2 vs 27.5, p = 0.0008) compared to patients in the BM-only group. Treatment with SOC CAR T yielded meaningful clinical outcomes in real-world RRMM patients with extraosseous EMD, though responses and survival outcomes were suboptimal compared to patients without EMD. The presence of only EMD but not PMD was associated with significantly worse survival outcomes following the CAR T infusion.


Assuntos
Imunoterapia Adotiva , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/terapia , Mieloma Múltiplo/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Imunoterapia Adotiva/métodos , Estudos Retrospectivos , Receptores de Antígenos Quiméricos/uso terapêutico , Adulto , Resultado do Tratamento , Padrão de Cuidado , Recidiva Local de Neoplasia/terapia
10.
J Adv Pract Oncol ; 14(3): 189-190, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37197722

RESUMO

This special issue of JADPRO includes summaries of select educational sessions presented at JADPRO Live 2022.

11.
J Adv Pract Oncol ; 14(3): 223-226, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37197733

RESUMO

In the popular biomarker-focused session at JADPRO Live 2022, presenters paired biomarkers with tumor types for which their expression is most commonly used to determine targeted therapy, identified key assays used to measure common biomarkers, and reviewed recommendations and guidelines for biomarker testing.

12.
Cancers (Basel) ; 15(7)2023 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-37046821

RESUMO

Multiple myeloma (MM) is the second most common hematologic malignancy in adults worldwide. Over the past few years, major therapeutic advances have improved progression-free and overall survival, as well as quality of life. Despite this recent progress, MM remains incurable in the vast majority of cases. Patients eventually relapse and become refractory to multiple drug classes, making long-term management challenging. In this review, we will focus on the treatment paradigm of relapsed/refractory MM (RRMM) in the era of advanced therapies emphasizing the available novel modalities that have recently been incorporated into routine practice, such as chimeric antigen receptor T-cell therapy, bispecific antibodies, and other promising approaches. We will also discuss major factors that influence the selection of appropriate drug combinations or cellular therapies, such as relapse characteristics, and other disease and patient related parameters. Our goal is to provide insight into the currently available and experimental therapies for RRMM in an effort to guide the therapeutic decision-making process.

13.
J Clin Med ; 12(17)2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37685606

RESUMO

Anti-B-cell maturation antigen therapies consisting of bispecific antibodies, antibody-drug conjugates, and chimeric antigen receptor T cells have shown promising results in relapsed refractory multiple myeloma (RRMM). However, the severe side effects include cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, cytopenia(s), infections, hemophagocytic lymphohistiocytosis, and organ toxicity, which could sometimes be life-threatening. This review focuses on these most common complications post-BCMA therapy. We discussed the risk factors, pathogenesis, clinical features associated with these complications, and how to prevent and treat them. We included four original studies for this focused review. All four agents (idecabtagene vicleucel, ciltacabtagene autoleucel, teclistamab, belantamab mafodotin) have received FDA approval for adult RRMM patients. We went through the FDA access data packages of the approved agents to outline stepwise management of the complications for better patient outcomes.

14.
J Adv Pract Oncol ; 13(3): 188-189, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35663161

RESUMO

This special issue of JADPRO includes summaries of educational sessions presented at JADPRO Live Virtual 2021.

15.
J Adv Pract Oncol ; 13(3): 213-216, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35663178

RESUMO

The COVID-19 pandemic has only further brought to light how racism, bias, and lack of equity can result in social injustice, morbidity, and mortality. A panel of four advanced practitioners convened at JADPRO Live Virtual 2021 to examine oncology advanced practitioners' capacity for enhancing equitable cancer care in the domains of care coordination and communication, clinical trials, and acknowledging and mitigating bias.

16.
J Adv Pract Oncol ; 13(Suppl 4): 23-30, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35937464

RESUMO

The overall care of patients with multiple myeloma can present similar challenges. However, disparities in health care require that providers consider each individual's unique circumstances. Disparities based on ethnic/racial group, religion, socioeconomic status, age, sexual orientation or gender identity, or other characteristics can lead to patients receiving less than optimal care and therefore poorer outcomes. Patients who have received more than two lines of therapy can acquire new genetic changes, accelerated cadence of relapse, and suffer from disease sequelae such as pain from prior or ongoing skeletal fractures, recurrent infections, and progressive decline in organ function. Numerous treatment options remain for patients in their first three relapses. Well-designed clinical trials with newer drugs are preferred. Clinicians should discuss clinical trial options and availability with all patients in spite of disparities that may exist. Patients facing disparities are at risk for suboptimal care and should be closely monitored and provided appropriate resources. Continued attention to disease and organ surveillance are critical throughout the course of the disease.

17.
J Adv Pract Oncol ; 13(Suppl 4): 15-21, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35937465

RESUMO

Multiple myeloma (MM) is a relapsing disease for many patients with multiple myeloma. At relapse, patients have many options for treatment once disease has progressed. Advanced practitioners are well suited to set expectations for ongoing therapy and underscore the importance of continued disease monitoring. Criteria for relapsed myeloma rely on biomarker and radiologic imaging, as well as physical exam and awareness of new bone pain or changes in physiologic function. The treatment of patients with relapsed MM requires a personalized approach and considers patient desires in regard to aggressiveness of therapy and willingness to participate in a clinical trial. The prognosis of patients with relapsed MM depends upon disease characteristics at baseline or throughout, as patients may acquire adverse cytogenetic abnormalities through various lines of treatment. Empowering patients to understand their diagnosis, interpret labs, and take an active role in treatment selection through shared decision-making can improve patients' quality of life and enhance adherence.

18.
J Adv Pract Oncol ; 13(Suppl 4): 7-14, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35937466

RESUMO

Multiple myeloma (MM) is an incurable plasma cell disorder that affects nearly 35,000 people annually. Over 149,000 individuals are estimated to live in the United States with MM. Research has generated a greater understanding of the pathology of this disease, now combined with mature clinical trial data that support the use of combination therapy in treatment. This article focuses on updated diagnosis, prognosis, and treatment of newly diagnosed patients. While the diagnosis of MM remains based on the 2014 International Myeloma Working Group (IMWG) guidelines, we review these and updated recommendations for the diagnosis and treatment of myeloma as well as relevant supportive care. The prognosis of patients with newly diagnosed MM relies heavily on the cytogenetic profile of the disease, along with other patient-specific risk factors. There are multiple first-line treatment options that combine three or four novel agents with the goal of reducing plasma cell burden and achieving minimal residual disease (MRD) negative status early in the treatment trajectory. Supportive care interventions aimed at minimizing the risk of infection and thromboembolic events, and protecting bone health are critical for maintaining quality of life and are as important as therapeutic treatment interventions.

19.
J Adv Pract Oncol ; 13(Suppl 4): 31-43, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35937467

RESUMO

Significant strides have been made in the management of patients living with myeloma. However, patients with multiply relapsed or refractory multiple myeloma (MM) have a shorter overall survival; therefore, new treatments with novel mechanisms of action are needed in this patient population. Patients with relapsing disease require a full restaging workup, including whole body imaging to evaluate for extramedullary disease and lytic bone lesions, as well as bone marrow biopsy with fluorescence in situ hybridization to determine if the patient has any new chromosomal changes that are present. Therapies utilizing the patient's immune cells, in particular T cells, provide a new option in relapsed/refractory myeloma. Treatment utilizing chimeric antigen receptor (CAR) T cells and/or bispecific antibody therapy provide excellent response rates. As such, advanced practitioners need to be aware of the potential toxicities associated with these newer treatments and how to manage them. This article will focus on the management of patients with relapsed and/or refractory disease who are undergoing treatment with either CAR T-cell therapy or bispecific T cell engager therapy.

20.
J Adv Pract Oncol ; 12(3): 236-237, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34084564

RESUMO

In this special issue of JADPRO, we highlight important takeaways for advanced practitioners from the educational sessions presented at our annual meeting, JADPRO Live.

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