RESUMO
BACKGROUND: The Center for International Blood and Marrow Transplant Research (CIBMTR) provides a 1-year overall survival calculator to estimate outcomes for individual patients before they undergo allogeneic hematopoietic cell transplantation (HCT) to inform risk. The calculator considers pre-HCT clinical and demographic characteristics, but not patient-reported outcomes (PROs). Because pre-HCT PRO scores have been associated with post-HCT outcomes, the authors hypothesized that adding PRO scores to the calculator would enhance its predictive power. METHODS: Clinical data were obtained from the CIBMTR and the Blood and Marrow Transplant Clinical Trials Network. The PRO measures used were the 36-Item Short Form Survey (SF-36) and the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation. One thousand thirty-three adult patients were included. RESULTS: When adjusted for clinical characteristics, the SF-36 physical component score was significantly predictive of 1-year survival (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.81-0.95; p = .0015), whereas the mental component score was not (HR, 1.02; 95% CI, 0.95-1.10; p = 0.6396). The baseline single general health question on the SF-36 was also significantly associated with mortality (HR, 1.91 for those reporting fair/poor health vs. good, very good, or excellent health; 95% CI, 1.33-2.76; p = .0005). The addition of PRO scores to the calculator did not result in a significant change in the model's predictive ability. Self-reported pre-HCT scores were strongly predictive of self-reported health status (odds ratio, 3.35; 95% CI, 1.66-6.75; p = .0007) and quality of life (odds ratio, 3.24; 95% CI, 1.93-5.41; p < .0001) after HCT. CONCLUSIONS: The authors confirmed the significant, independent association of pre-HCT PRO scores with overall survival, although adding PRO scores to the survival calculator did not improve its performance. They also demonstrated that a single general health question was as accurate as the full measure for predicting survival, an important finding that may reduce respondent burden and promote its inclusion in routine clinical practice. Validation of these findings should be performed.
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Transplante de Células-Tronco Hematopoéticas , Medidas de Resultados Relatados pelo Paciente , Transplante Homólogo , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Qualidade de Vida , Adulto JovemRESUMO
Autologous haematopoietic cell transplantation (autoHCT) and continuous post-transplant maintenance therapy are the standard of care in transplant-eligible multiple myeloma (MM) patients. We sought to describe symptom burden and identify symptom clusters occurring in MM patients after autoHCT using data from the BMT CTN 0702 randomized controlled trial comparing the outcomes of three treatment interventions after an autoHCT in 758 MM patients. We analysed individual transplant-related symptoms assessed via the FACT-BMT questionnaire at enrolment and annually for 4-year post-autoHCT. We also described the effect the individual symptoms and symptom clusters have on quality of life (QoL). We identified three stable symptom clusters: malaise symptom cluster (lack of energy, feeling ill, having pain, experiencing nausea, loss of appetite), physical symptom cluster (having skin problems, tremors, worsening eyesight, change in taste, shortness of breath, frequent colds) and emotional symptom cluster (feeling sad, being nervous, experiencing sleep problems). Malaise and emotional symptom clusters have a greater impact on QoL than the physical symptoms cluster. Identifying these symptoms warrant additional support in terms of psychosocial support, in addition to treatment of the physical symptoms themselves.
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Mieloma Múltiplo , Humanos , Mieloma Múltiplo/terapia , Dor , Qualidade de Vida/psicologia , Sobreviventes , SíndromeRESUMO
Chimeric antigen receptor T-cell (CAR-T) therapy and bispecific T-cell engagers (BsAb) have emerged as promising immunotherapeutic modalities in patients with relapsed and/or refractory multiple myeloma (RRMM). However, there is limited data on the safety and efficacy of CAR-T and BsAb therapies in MM patients with a prior history of allogeneic transplantation (allo-HCT). Thirty-three MM patients with prior allo-HCT received CAR-T (n = 24) or BsAb (n = 9) therapy. CAR-T therapy demonstrated an ORR of 92% (67% ≥ CR), and 73% were MRD negative. BsAb therapy resulted in an ORR of 44% (44% ≥ CR) and 44% MRD negative. Safety analysis showed grade ≥3 AEs in 92% of CAR-T and 56% of BsAb patients. Cytokine release syndrome (CRS) occurred in 83% of CAR-T and 78% of BsAb recipients, while immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in three CAR-T patients. Infections of grade ≥3 were reported in 50% of CAR-T and 44% of BsAb recipients. No exacerbation of graft-versus-host disease occurred except in one BsAb recipient. CAR-T and BsAb therapies appear to be feasible, safe and provide deep and durable responses in MM patients with prior allo-HCT.
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Mieloma Múltiplo , Neoplasias de Plasmócitos , Receptores de Antígenos Quiméricos , Humanos , Imunoterapia Adotiva , Transplante HomólogoRESUMO
There is a paucity of granular data on infection risk with B-cell maturation antigen (BMCA) and GPRC5D bispecific antibodies (bsAb) in relapsed/refractory multiple myeloma (RRMM). The aim of our multi-institutional study was to characterize the incidence, etiologies, and risk factors of infections from the start of therapy to the last follow-up or 90 days after study exit. A total of 66 patients received BCMA bsAb monotherapy, 15 GPRC5D bsAb monotherapy, and 15 GPRC5D bsAb combination therapy with daratumumab and/or pomalidomide. While the infection rate per 100 days was 0.57 for BCMA bsAb, it was 0.62 for GPRC5D bsAb combination and 0.13 for GPRC5D bsAb monotherapy; P=0.05. The proportion of infections that were grade ≥3 was higher in the BCMA bsAb group compared to the GPRC5D groups (58% vs. 36%; P=0.04). Grade 5 events were observed in 8% (n=8) of the patients, all treated with BCMA bsAb. The 9 month cumulative incidence of any grade of infection was similar in the BCMA and GPRC5D-combination groups (57% and 62%) and significantly higher than in the GPRC5D-mono group (16%); P=0.012. The cumulative incidence of grade ≥3 infections was highest in the BCMA group reaching 54% at 18 months; P=0.06. Multivariate analysis showed that BCMA bsAb therapy or GPRC5D combination therapy, history of previous infections, baseline lymphopenia, and baseline hypogammaglobulinemia were significantly associated with a higher risk of grade ≥3 infections. Our results indicate that BCMA bsAb and GPRC5D-combination therapies in RRMM are associated with higher cumulative incidence of infection and grade ≥3 infection compared to GPRC5D bsAb mono.
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Anticorpos Biespecíficos , Mieloma Múltiplo , Neoplasias de Plasmócitos , Humanos , Mieloma Múltiplo/tratamento farmacológico , Anticorpos Biespecíficos/efeitos adversos , Antígeno de Maturação de Linfócitos B , Terapia Combinada , Receptores Acoplados a Proteínas GRESUMO
OBJECTIVE: To evaluate the psychometric properties of the AL-PROfile, a patient-reported outcome measure combining the Patient-Reported Outcomes Measurement Information System (PROMIS)-29, two items from PROMIS Cognitive Function, and select Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) items. METHODS: Content validity was assessed through cognitive debriefing interviews of 20 patients who completed the AL-PROfile (Study 1). Study 2 involved 297 participants who completed the AL-PROfile and Medical Outcomes Study 36-item Short-Form Health Survey (SF-36). Reliability (internal consistency and test-retest reliability) and validity (convergent and discriminant validity, known groups validity by stage/organ involvement) were calculated. RESULTS: Study 1 participants found the AL-PROfile straightforward confirming the relevance of the included content. Some felt that certain questions were not related to their amyloidosis experience. Study 2 demonstrated acceptable internal consistency for all domains/items except PROMIS Cognitive Function and acceptable test-retest reliability for all except PROMIS Cognitive Function and PRO-CTCAE nausea. Large correlations were seen for the same domain across measures while correlations for divergent domains within a measure and different domains across different measures were small. The PRO-CTCAE items showed small to medium correlations with each other and with PROMIS and SF-36 domains. Stage was associated with physical function, fatigue, social roles, swelling, and shortness of breath scores. CONCLUSION: The AL-PROfile has acceptable reliability and validity for use in systemic light chain amyloidosis patients.
Assuntos
Amiloidose de Cadeia Leve de Imunoglobulina , Medidas de Resultados Relatados pelo Paciente , Psicometria , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Idoso , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Qualidade de Vida , Inquéritos e Questionários , Adulto , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Lenalidomide maintenance after autologous stem cell transplant (ASCT) in multiple myeloma (MM) results in superior progression-free survival and overall survival. However, patients with high-risk multiple myeloma (HRMM) do not derive the same survival benefit from lenalidomide maintenance compared with standard-risk patients. The authors sought to determine the outcomes of bortezomib-based maintenance compared with lenalidomide maintenance in patients with HRMM undergoing ASCT. METHODS: In total, the authors identified 503 patients with HRMM who were undergoing ASCT within 12 months of diagnosis from January 2013 to December 2018 after receiving triplet novel-agent induction in the Center for International Blood and Marrow Transplant Research database. HRMM was defined as deletion 17p, t(14;16), t(4;14), t(14;20), or chromosome 1q gain. RESULTS: Three hundred fifty-seven patients (67%) received lenalidomide alone, and 146 (33%) received bortezomib-based maintenance (with bortezomib alone in 58%). Patients in the bortezomib-based maintenance group were more likely to harbor two or more high-risk abnormalities and International Staging System stage III disease (30% vs. 22%; p = .01) compared with the lenalidomide group (24% vs. 15%; p < .01). Patients who were receiving lenalidomide maintenance had superior progression-free survival at 2 years compared with those who were receiving either bortezomib monotherapy or combination therapy (75% vs. 63%; p = .009). Overall survival at 2 years was also superior in the lenalidomide group (93% vs. 84%; p = .001). CONCLUSIONS: No superior outcomes were observed in patients with HRMM who received bortezomib monotherapy or (to a lesser extent) in those who received bortezomib in combination as maintenance compared with lenalidomide alone. Until prospective data from randomized clinical trials are available, post-transplant therapy should be tailored to each patient with consideration for treating patients in clinical trials that target novel therapeutic strategies for HRMM, and lenalidomide should remain a cornerstone of treatment.
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Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/terapia , Lenalidomida/uso terapêutico , Bortezomib/uso terapêutico , Estudos Prospectivos , Transplante de Células-Tronco Hematopoéticas/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante Autólogo/métodos , Dexametasona/uso terapêuticoRESUMO
Chimeric antigen receptor T (CAR T) cell and bispecific antibody therapies have shown unprecedented efficacy in heavily pretreated patients with multiple myeloma (MM). However, their use is associated with a significant risk of severe infections, which can be attributed to various factors such as hypogammaglobulinemia, neutropenia, lymphopenia, T-cell exhaustion, cytokine-release syndrome and immune-effector cell-associated neurotoxicity syndrome. As these therapies have been recently approved by regulatory agencies, it is crucial to establish practical guidelines for infection monitoring and prevention until robust data from prospective clinical trials become available. To address this issue, a panel of experienced investigators from the Academic Consortium to Overcome Multiple Myeloma through Innovative Trials (COMMIT) developed consensus recommendations for mitigating infections associated with CAR T-cell and bispecific antibody therapies in MM patients.
Assuntos
Anticorpos Biespecíficos , Leucopenia , Mieloma Múltiplo , Receptores de Antígenos Quiméricos , Humanos , Receptores de Antígenos Quiméricos/uso terapêutico , Linfócitos T , Mieloma Múltiplo/tratamento farmacológico , Estudos Prospectivos , Imunoterapia Adotiva/efeitos adversos , Anticorpos Biespecíficos/efeitos adversos , Leucopenia/etiologia , Antígeno de Maturação de Linfócitos BRESUMO
Survival has improved in patients diagnosed with multiple myeloma (MM) over the last two decades; however, there remains a paucity of data on the causes of death in MM patients and whether causes of death change during the disease trajectory. We conducted a retrospective population-based study to evaluate the rates of MM-specific versus non-MM cause of death and to identify factors associated with cause-specific death in MM patients, stratified into autologous stem cell transplant (ASCT) and non-ASCT cohorts. A total of 6,677 patients were included, 2,576 in the ASCT group and 4,010 in the non-ASCT group. Eight hundred and seventy-three (34%) ASCT patients and 2,787 (68%) non-ASCT patients died during the follow-up period. MM was the most frequent causes of death, causing 74% of deaths in the ASCT group and 67% in the non-ASCT group. Other cancers were the second leading causes of death, followed by cardiac and infectious diseases. Multivariable analysis demonstrated that a more recent year of diagnosis and novel agent use within 1 year of diagnosis were associated with a decreased risk of MM-specific death, whereas a history of previous non-MM cancer, older age, and the presence of CRAB criteria at diagnosis increased the risk of non-MM death. Our data suggests that despite improvement in MM outcomes in recent years, MM remains the greatest threat to overall survival for patients. Further advances in the development of effective MM therapeutic agents in both ASCT and non-ASCT populations and patient access to them is needed to improve outcomes.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Estudos Retrospectivos , Transplante Autólogo , Transplante de Células-TroncoRESUMO
OBJECTIVE: To assess the impact of organ involvement on patient-reported outcomes (PROs) in light chain (AL) amyloidosis. METHODS: PROs were evaluated using the KCCQ-12, PROMIS-29 + 2, and SF-36 in individuals with AL amyloidosis. The 2004 Mayo system was used to stage disease and cardiac, neurologic, and renal involvement was considered. Global physical and mental health (MH) scores, physical function (PF), fatigue, social function (SF), pain, sleep, and MH domains were evaluated. Effect sizes between scores were measured using Cohen's d. RESULTS: Of 297 respondents, the median age at diagnosis was 60 years with 58% cardiac, 58% renal, and 30% neurologic involvement. Fatigue, PF, SF, and global physical health with PROMIS and SF-36 discriminated the most by stage. Significant discrimination in PROMIS and/or SF-36 was seen in PF, fatigue, and global physical health with cardiac involvement. For neurologic involvement, PF, fatigue, SF, pain, sleep, global physical, and MH with PROMIS and role physical, vitality, pain, general health, and physical component summary with SF-36 were discriminatory. For renal amyloid, pain by SF-36 and PROMIS, and SF-36 MH and role emotional subscales were significant. CONCLUSIONS: Fatigue, PF, SF, and global physical health can discriminate stage, cardiac and neurologic, but not renal, AL amyloidosis involvement.
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Amiloidose de Cadeia Leve de Imunoglobulina , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Amiloidose de Cadeia Leve de Imunoglobulina/terapia , Gravidade do Paciente , Medidas de Resultados Relatados pelo Paciente , Emoções , Fadiga/diagnóstico , Fadiga/etiologiaRESUMO
For myelodysplastic syndrome (MDS), allogeneic hematopoietic cell transplantation (alloHCT) is the only available curative therapy. The Blood and Marrow Transplant Clinical Trials Network study 1102 (BMT CTN 1102, NCT02016781) was a multicenter, biologic assignment trial based on matched donor availability in adults aged 50-75 with higher risk de novo MDS who were candidates for reduced-intensity conditioning (RIC) alloHCT. The primary analysis showed that those who received alloHCT had a survival benefit, but whether this is at the cost of worse quality of life (QOL) has not been described in detail. English- and Spanish-speaking trial participants completed the Functional Assessment of Cancer Therapy-General (FACT-G), the SF-36, and the EQ-5D, at enrollment, every 6 months until 24 months, and 36 months. We compared patient-reported outcome (PRO) scores between study arms using an inverse probability weighted-independent estimating equation (IPW-IEE) model. Between January 2014 and November 2018, 384 subjects (median age 66.7 years, range: 50.1-75.3) enrolled at 34 centers. PRO completion rates were generally high at 65%-78%. The PRO trajectories for both arms were similar, with most decreasing or stable from baseline to 6 months and improving thereafter. Baseline PRO scores were the most consistent independent predictors of subsequent QOL outcomes and survival, even after controlling for clinical and patient-level factors. For older adults with MDS, the survival advantage associated with donor availability and alloHCT did not come at the cost of worse QOL. These results should reassure older patients and clinicians who prefer a curative approach to treating MDS.
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Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas , Humanos , Idoso , Qualidade de Vida , Condicionamento Pré-Transplante/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Síndromes Mielodisplásicas/terapia , Doadores de TecidosRESUMO
Early autologous hematopoietic cell transplantation (AHCT) with post-transplant maintenance therapy is standard of care in multiple myeloma (MM). While short-term quality of life (QOL) deterioration after AHCT is known, the long-term trajectories and symptom burden after transplantation are largely unknown. Toward this goal, a secondary analysis of QOL data of the BMT CTN 0702, a randomized controlled trial comparing outcomes of three treatment interventions after a single AHCT (N = 758), was conducted. FACT-BMT scores up to 4 years post-AHCT were analyzed. Symptom burden was studied using responses to 17 individual symptoms dichotomized as 'none/mild' for scores 0-2 and 'moderate/severe' for scores of 3 or 4. Patients with no moderate/severe symptom ratings were considered to have low symptom burden at 1-year. Mean age at enrollment was 55.5 years with 17% African Americans. Median follow-up was 6 years (range, 0.4-8.5 years). FACT-BMT scores improved between enrollment and 1-year and remained stable thereafter. Low symptom burden was reported by 27% of patients at baseline, 38% at 1-year, and 32% at 4 years post-AHCT. Predictors of low symptom burden at 1-year included low symptom burden at baseline: OR 2.7 (1.8-4.1), p < 0.0001; older age: OR 2.1 (1.3-3.2), p = 0.0007; and was related to being employed: OR 2.1 (1.4-3.2), p = 0.0004). We conclude that MM survivors who achieve disease control after AHCT have excellent recovery of FACT-BMT and subscale scores to population norms by 1-year post-transplant, though many patients continue to report moderate to severe severity in some symptoms at 1-year and beyond.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Humanos , Pessoa de Meia-Idade , Mieloma Múltiplo/terapia , Qualidade de Vida , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante AutólogoRESUMO
BACKGROUND: We conducted a cross-sectional study to characterize health-related quality of life and symptom burden in individuals living with light chain (AL) amyloidosis. METHODS: Members of the Amyloidosis Support Groups, Inc. with AL amyloidosis who consented to this IRB-approved survey provided information on their amyloidosis diagnosis, treatment, symptoms, and functioning. HRQL was measured using PROMIS and PRO-CTCAE questionnaires. RESULTS: Among 297 participants who responded, the median age at diagnosis was 60 years (23-82) with 52% female and 90% white race. There were 69% AL (lambda) and 39% reported 3 or more organs involved with amyloidosis (58% cardiac, 58% renal, 30% neurological AL). Time from diagnosis was less than 2 years in 64 (22%), 2-5 years in 105 (36%), > 5 years in 126 (43%), and unknown in 2 (< 1%) individuals. Therapy included prior chemotherapy in 88% and stem cell transplant in 52%. Fifty percent of the cohort was on active treatment. Multiple domains were impaired in AL amyloidosis compared to the general population, including physical function, fatigue, and social roles. While highest among those within 2 years of diagnosis, high symptom burden was also seen in long-term survivors. A trend to decreased severity and number of impaired symptoms was seen with longer treatment-free interval but many symptoms remained persistent. CONCLUSIONS: Significant and persistent symptom burden is seen in AL amyloidosis. Patient-reported outcomes should be routinely measured and used to provide best supportive care to all AL amyloidosis patients, including long-term survivors and those not on active therapy.
Assuntos
Amiloidose , Amiloidose de Cadeia Leve de Imunoglobulina , Humanos , Feminino , Masculino , Amiloidose de Cadeia Leve de Imunoglobulina/terapia , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Estudos Transversais , Qualidade de Vida/psicologia , Amiloidose/tratamento farmacológico , Medidas de Resultados Relatados pelo PacienteRESUMO
Patient-reported outcome measures (PROMs), which are measures of symptom burden, health-related quality of life (HRQoL), and therapy effectiveness have become increasingly important in clinical research. They are unique in that they are reported directly from the patient, without clinician interpretation, thereby avoiding clinician bias. With an increased focus on the patient at the center of health care, PROMs have been increasingly incorporated into clinical research, systematic reviews, and clinical guidelines. Despite the recognition of the importance of including PROMs into clinical haematologic cancer research, barriers have prevented their integration into cancer research. This review highlights the value of including PROMs into clinical haematologic cancer research and addresses the methodological challenges in using and evaluating PROMs. We propose important questions for the malignant haematologist to consider when designing or evaluating a study that includes PROMs.
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Neoplasias Hematológicas , Medidas de Resultados Relatados pelo Paciente , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/epidemiologia , Neoplasias Hematológicas/terapia , Humanos , Qualidade de VidaRESUMO
The incremental impact of autologous hematopoietic cell transplantation (AHCT) on disease burden with quadruplet induction in newly diagnosed multiple myeloma (NDDM) can be reappraised with the serial assessment of minimal residual disease (MRD). We describe the impact of AHCT on MM burden assessed by next-generation sequencing (NGS) for patients enrolled in a clinical trial utilizing quadruplet induction, AHCT, followed by MRD-adapted consolidation. We describe quantitative changes in MRD burden with AHCT and explore patient and disease features influencing the magnitude of MRD reduction with AHCT. Among 123 included patients, 109 underwent AHCT and had MRD assessment pre and post AHCT. Forty percent achieved MRD < 10-5 post-induction, increasing to 70% after AHCT. Of the 65 patients (60%) who remained MRD positive post-induction, 54 (83%) had a reduction in MRD burden with AHCT. The median reduction in MRD with AHCT was 1.10 log10 (range, -1.26 to 3.41). Patients with high-risk cytogenetic abnormalities (HRCA) had greater reduction in MRD burden (p = .02) after AHCT. Median relative reduction was 0.91 log10 (range, -0.75 to 2.14), 1.26 log10 (range, -0.21 to 3.26) and 1.34 log10 (range, -1.28 to 3.41) for patients with 0, 1 and 2+ HRCA, respectively. The presence of HRCA was the only factor associated with greater than 1 log10 reduction in MRD burden with AHCT. Serial NGS MRD demonstrates the incremental effect of AHCT in MM marrow burden in the context of quadruplet induction, particularly in high-risk MM.
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Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Efeitos Psicossociais da Doença , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/genética , Mieloma Múltiplo/terapia , Neoplasia Residual/diagnóstico , Transplante AutólogoRESUMO
PURPOSE: Multiple myeloma (MM) is the second most common hematologic malignancy in the USA, with higher rates observed in older adults and African Americans (AA). Survivors experience fatigue, bone pain, reduced functioning, and obesity, highlighting the value of developing lifestyle interventions for this diverse group. This study explores lifestyle behaviors and supportive care needs to inform future programs tailored to the MM community. METHODS: MM survivors, ≥ 100 days post autologous stem cell transplant (ASCT) with a BMI ≥ 20 kg/m2, were recruited from two university hospitals. Diet, physical activity, and quality of life (QOL) were measured using validated measures. Qualitative interviews gathered information on survivorship needs and interests related to supportive interventions. Quantitative data was analyzed using descriptive statistics; qualitative data were analyzed using deductive strategies. RESULTS: Seveny-two MM survivors participated (65% white, 35% black). Participants were 62.5 ± 15.8 years of age. Fifty percent were classified as obese and 65% were insufficiently active. Participants reported diets high in added sugars and saturated fats. QOL measures indicated clinically significant challenges in physical and sexual function. Most (87%) were interested in a lifestyle program. Predominant themes regarding survivors' desires for a lifestyle program included social support, guided exercise, meal preparation support, and disease management information. CONCLUSION: This study demonstrates the need for and interest in lifestyle change support among a racially diverse sample of MM survivors. Interventions that are group-based, target knowledge gaps, social connections, accountability, and provide structured framework with professional instruction will best address the needs of this survivor population.
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Mieloma Múltiplo , Qualidade de Vida , Humanos , Idoso , Estudos de Viabilidade , Mieloma Múltiplo/terapia , Estilo de Vida , Comportamentos Relacionados com a Saúde , Obesidade/terapiaRESUMO
BACKGROUND: Light chain (AL) amyloidosis is a plasma cell neoplasm associated with high early mortality and severe morbidity that can cause severe disability. We explored the impact of AL amyloidosis on symptoms and well-being from the perspectives of patients and health care providers who regularly care for AL patients. We intended to develop a conceptual understanding of patient-reported outcomes in AL amyloidosis to identify the context of use and concept of interest for a clinical outcome assessments tool in this disease. METHOD: Twenty patients and ten professionals were interviewed. Patient interviews captured the spectrum of amyloidosis experience including time from diagnosis, type of organ involvement, and presence and type of treatment received. Interviews with professionals included physicians, advanced practice providers, registered nurse, and a patient advocate; these interviews covered similar topics. RESULTS: The impact of AL amyloidosis on patients' life was multidimensional, with highly subjective perceptions of normality and meaning. Four major themes from patients and experts included diagnosis of AL amyloidosis, living with AL amyloidosis, symptom burden, and social roles. Barriers to patient-reported outcomes data collection in patients were additionally explored from experts. The themes provide a comprehensive understanding of the important experiences of symptom burden and its impact on daily life from AL amyloidosis patients' and from the perspectives of professionals who care for patients with AL amyloidosis. CONCLUSION: These findings further the conceptual understanding and identification of a preliminary model of concept of interest for development of a clinical outcome assessments tool for AL amyloidosis.
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Amiloidose , Qualidade de Vida , Amiloidose/complicações , Pessoal de Saúde , Humanos , Medidas de Resultados Relatados pelo Paciente , Pesquisa Qualitativa , Qualidade de Vida/psicologiaRESUMO
Successful hematopoietic cell transplantation (HCT) depends on rapid engraftment of the progenitor and stem cells that will reestablish hematopoiesis. Rap1A and Rap1B are two closely related small GTPases that may affect platelet and neutrophil engraftment during HCT through their roles in cell adhesion and migration. ß-adrenergic signaling may regulate the participation of Rap1A and Rap1B in engraftment through their inhibition or activation. We conducted a correlative study of a randomized controlled trial evaluating the effects of the nonselective ß-antagonist propranolol on expression and prenylation of Rap1A and Rap1B during neutrophil and platelet engraftment in 25 individuals receiving an autologous HCT for multiple myeloma. Propranolol was administered for 1 week prior to and 4 weeks following HCT. Blood was collected 7 days (baseline) and 2 days (Day -2) before HCT, and 28 days after HCT (Day +28). Circulating polymorphonuclear cells (PMNC) were isolated and analyzed via immunoblotting to determine levels of prenylated and total Rap1A versus Rap1B. Twelve participants were randomized to the intervention and 13 to the control. Rap1A expression significantly correlated with Rap1B expression. Rap1B expression significantly correlated with slower platelet engraftment; however, this association was not observed in the propranolol-treated group. There were no significant associations between neutrophil engraftment and Rap1A or Rap1B expression. Post hoc exploratory analyses did not reveal an association between social health variables and Rap1A or Rap1B expression. This study identifies a greater regulatory role for Rap1B than Rap1A in platelet engraftment and suggests a possible role for ß-adrenergic signaling in modulating Rap1B function during HCT.
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Transplante de Células-Tronco Hematopoéticas , Propranolol , Adrenérgicos , Humanos , Propranolol/farmacologia , Transdução de Sinais/fisiologia , Proteínas rap de Ligação ao GTP/metabolismo , Proteínas rap1 de Ligação ao GTP/metabolismoRESUMO
BACKGROUND: Consolidative autologous hematopoietic stem cell transplantation (AHCT) is commonly used for patients with multiple myeloma (MM). We studied AHCT use and outcomes in patients with MM ≥75 years old. METHODS: Patients with MM ≥75 years old receiving AHCT between 2013 and 2017 in the United States were identified using the Center for International Blood and Marrow Transplant Research database. Relapse and/or progression (REL), progression-free survival (PFS), and overall survival (OS) were modeled using Cox proportional hazards models. Covariates used were age, sex, Karnofsky performance score (KPS), HCT-comorbidity index (HCT-CI), International Staging System and/or Durie-Salmon stage, high-risk cytogenetics, melphalan dose, and disease status at and 1 year after transplant. AHCT utilization rate using the Surveillance, Epidemiology, and End Results database was used to estimate specific incidence among ≥75 years old by race and gender. RESULTS: Of 360 patients, 63% were male, 84% were White, 56% had KPS <90, and 57% had HCT-CI ≥3. The 100-day transplant-related mortality was 1% (0%-2%) with a 2-year REL rate of 27% (95% confidence interval [CI], 22%-33%), PFS of 66% (95% CI, 60%-72%), and OS of 83% (95% CI, 78%-87%). On multivariate analysis, only high-risk cytogenetics was associated with REL risk and decreased PFS. In White males, transplant utilization rate was 5.2%-5.8% compared to 3.5%-4.0% in African American males (P = .02). There was 3.37-3.79% transplant utilization in White females compared to 1.88-2.12% in African American females (P < .01). CONCLUSIONS: The use of AHCT was associated with excellent 2-year outcomes in this selected MM population ≥75 years old. Transplant utilization for patients ≥75 years old remains low with significant racial and gender disparities.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Idoso , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Melfalan/uso terapêutico , Mieloma Múltiplo/terapia , Recidiva Local de Neoplasia , Condicionamento Pré-Transplante/métodos , Transplante Autólogo/métodos , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Multiple myeloma (MM) with the translocation t(11;14) may have inferior outcomes in comparison with other standard-risk MM, and it has been suggested to portend a worse prognosis in African Americans in comparison with Whites. This study used the Center for International Blood and Marrow Transplant Research (CIBMTR) database to examine the impact of t(11;14) on the clinical outcomes of patients with MM of African American and White descent. METHODS: This study evaluated 3538 patients who underwent autologous hematopoietic cell transplantation (autoHCT) for MM from 2008 to 2016 and were reported to the CIBMTR. Patients were analyzed in 4 groups: African Americans with t(11;14) (n = 117), African Americans without t(11;14) (n = 968), Whites with t(11;14) (n = 266), and Whites without t(11;14) (n = 2187). RESULTS: African Americans with t(11;14) were younger, had lower Karnofsky scores, and had more advanced stage MM with a higher Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI). Fewer African Americans with t(11;14) (21%) had a coexistent high-risk marker in comparison with Whites with t(11;14) (27%). In a multivariate analysis, race and t(11;14) had no association with progression-free survival. However, overall survival was superior among African Americans with t(11;14) in comparison with Whites with t(11;14) (hazard ratio, 0.53; 95% confidence interval, 0.30-0.93; P = .03). Survival was also associated with female sex, stage, time from diagnosis to transplant, a low HCT-CI, and receipt of maintenance. CONCLUSIONS: Race may have a differential impact on the survival of patients with t(11;14) MM who undergo autoHCT and needs to be further studied.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/epidemiologia , Mieloma Múltiplo/terapia , Translocação Genética/genética , Condicionamento Pré-Transplante/métodos , Transplante Autólogo/métodos , Negro ou Afro-Americano , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Estudos Prospectivos , Estados Unidos , População BrancaRESUMO
Many patients with multiple myeloma (MM) eventually relapse even after allogeneic hematopoietic cell transplantation (alloHCT) for curative intent. Over the past decade, outcomes for patients with MM have improved significantly with the availability of new therapies, including next-generation proteasome inhibitors, immunomodulatory agents, and, more recently, monoclonal antibodies. Although several published studies have evaluated the outcomes of alloHCT for MM, the data on survival outcomes in patients with MM experiencing disease relapse following alloHCT are limited. In addition, the predictors for postrelapse survival in these patients are not known. In this study, we examined the outcomes of a single-center cohort of 60 patients with MM who experienced relapse or progression after alloHCT. In addition, we evaluated the use of salvage regimens for treatment of relapsed MM and analyzed the predictors for improved postrelapse survival. After a median follow-up of 2.2 years from the time of relapse, the median duration of postrelapse survival was 1.8 years (95% confidence interval [CI], 1.2 to 5.0 years). Patients received a median of 3 lines of therapy (range, 0 to 10) for treatment of MM beyond the post-alloHCT relapse/progression. Multivariate analysis identified cytogenetic risk (standard risk versus high risk; hazard ratio [HR], .34; P = .01), time to relapse after alloHCT (>12 months versus ≤12 months: HR, .41; P = .04), and occurrence of acute graft-versus-host disease (GVHD) before relapse (GVHD versus no GVHD: HR, 2.89; P = .01) significantly affected postrelapse survival. These data illustrate that long-term myeloma control and survival is attainable in those relapsing/progressing after alloHCT and suggest that the synergism between novel therapies and the allogeneic immune platform is the key to improved survival in this high-risk patient population.