Survival Trends in Young Patients With Multiple Myeloma: A Focus on Racial-Ethnic Minorities

IntroductionOutcomes in multiple myeloma (MM) have improved significantly over time. This is true overall for all patients as well as patient subgroups based on age and race/ethnicity. Despite this, disparities are noted in outcomes when looking at racial subgroups.Materials and MethodsWe performed an analysis from the population-based Surveillance, Epidemiology, and End Results (SEER) database to evaluate improvement in relative survival rates (RSRs) for young (≤ 40 years at the time of MM diagnosis) and older (> 40 years at the time of MM diagnosis) over time by race/ethnicity, specifically focusing on Hispanic patients with MM. Expected survival was estimated using the age- and gender-specific death rates from the United States population. RSR was provided as the ratio of the observed to expected survival at individual time points. Five-year and 10-year RSRs were calculated for patients based on treatments modalities available in various time periods.ResultsWe identified a total of 89,451 patients with MM in SEER, of which 1460 patients formed the young patients with MM (≤ 40 years) cohort. Five- and 10-year RSR improved significantly over time for all patients and older patients (> 40 years) by race (all P < .001). Evaluating the younger patients, RSR improved significantly for non-Hispanic whites and non-Hispanic blacks, but not for Hispanics. This was true for the 5-year (P = .08) and 10-year (P = .13) RSRs.ConclusionWe report a lack of significant benefit in long-term outcomes for younger Hispanic patients with MM over time. This could be owing to multifactorial causes that need to be addressed to mitigate outcome disparities.     

Rates of Influenza and Pneumococcal Vaccination and Correlation With Survival in Multiple Myeloma Patients

BackgroundInfections are a common reason for hospitalization and death in multiple myeloma (MM). Although pneumococcal vaccination (PV) and influenza vaccination (FV) are recommended for MM patients, data on vaccination status and outcomes are limited in MM.Materials and MethodsWe utilized data from the global, prospective, observational INSIGHT MM study to analyze FV and PV rates and associated outcomes of patients with MM enrolled 2016-2019.ResultsOf the 4307 patients enrolled, 2543 and 2500 had study-entry data on FV and PV status. Overall vaccination rates were low (FV 39.6%, PV 30.2%) and varied by region. On separate multivariable analyses of overall survival (OS) by Cox model, FV in the prior 2 years and PV in the prior 5 years impacted OS (vs. no vaccination; FV: HR, 0.73; 95% CI, 0.60-0.90; P = .003; PV: HR, 0.51; 95% CI, 0.42-0.63; P < .0001) when adjusted for age, region, performance status, disease stage, cytogenetics at diagnosis, MM symptoms, disease status, time since diagnosis, and prior transplant. Proportions of deaths due to infections were lower among vaccinated versus non-vaccinated patients (FV: 9.8% vs. 15.3%, P = .142; PV: 9.9% vs. 18.0%, P = .032). Patients with FV had generally lower health resource utilization (HRU) versus patients without FV; patients with PV had higher or similar HRU versus patients without PV.ConclusionVaccination is important in MM and should be encouraged. Vaccination status should be recorded in prospective clinical trials as it may affect survival. This trial was registered at www.clinicaltrials.gov as #NCT02761187.     

多发性骨髓瘤患者预后的社会经济学因素分析及特异性生存率预测模型的构建

目的 探究社会经济学因素对多发性骨髓瘤（MM）患者预后的影响并构建预测模型评估患者骨髓瘤特异性生存（MSS）。方法 由SEER数据库纳入32 625例2007年1月至2016年12月间诊断为MM的患者。Cox回归模型分析MSS的预测因素,森林图展现多因素亚组分析的结果,多因素Cox分析中确定的显著变量用来构建列线图。曲线下面积（AUC）和校准图评估列线图的预测性能,利用限制性三次样条曲线构建基于列线图评分的风险分层系统。结果 患者按其社会经济地位（SES）的高低分为五组,SES更高的群体中白人、有保险者、已婚人群和城市居民的比例相对更高。单因素及多因素Cox分析表明年龄、性别、种族、婚姻状态、保险状况和SES是患者MSS独立预后影响因素（均P<0.001）。亚组分析显示随着SES降低,MSS风险增加的线性趋势在白人、已婚、有保险和城市患者中最为显著（均P<0.001）。构建的列线图在训练集和验证集中均展现出良好的区分度和准确性,其预测3年、5年和8年MSS的AUC值分别为0.701、0.709和0.722。根据列线图总分和风险比建立了风险分层模型,所划分的三类不同风险等级组...     

Autologous Hematopoietic Cell Transplantation in Patients With Multiple Myeloma: Effect of Age

BackgroundIn the novel and pre–novel agent era, high-dose therapy, followed by autologous hematopoietic cell transplantation (AHCT), has been shown to prolong survival in patients with multiple myeloma (MM) in randomized trials. However, these trials only included patients aged ≤ 65 years. Given that the median age at diagnosis is 66 years, it is important to know the outcomes of AHCT in older patients. Similarly, definite outcomes of AHCT in very young patients (aged < 50 years) are also lacking because they represent a very small proportion of patients in clinical trials.Materials and MethodsWe analyzed a consecutive cohort of patients with MM receiving AHCT from 2000 to 2015 in 2 different age groups, older (> 70 years) and younger (≤ 50 years), and compared the outcomes. The primary objectives were to assess overall survival, progression-free survival (PFS), and nonrelapse mortality in these 2 groups.ResultsOf the 191 patients, 86 were young (age ≤ 50 years) and 105 were old (age > 70 years). The younger patients had better performance status and a lower comorbidity index, and most of the older patients had received a melphalan dose of 140 to 180 mg/m². The median follow-up period for the young group was 33 months (range, 2-164 months) compared with 22.5 months (range, 3-133 months) in the old group (P = .02). The PFS rate at 1 year was 60% (95% confidence interval [CI], 46%-72%) for the young group and 58% (95% CI, 45%-69%) for the old group. The overall survival rate at 1 year was 92% (95% CI, 84%-96%) for the young group and 85% (95% CI, 76%-91%) for the old group. On multivariate analysis, age did not have any effect on survival (P = .82); however, the patients with high-risk cytogenetics (hazard ratio [HR], 2.2; 95% CI, 1.06-4.6; P = .04) had worse overall mortality. High-risk cytogenetics (HR, 1.2; 95% CI, 1.1-3.5; P = .004) and no disease response or progressive disease at transplantation (HR, 5.0; 95% CI, 1.8-13.5; P = .02) were significantly associated with worse PFS.ConclusionAge should not be a limiting factor in considering the modality of AHCT. However, younger patients might also benefit from additional novel treatment approaches in the setting of clinical trials, given their similar outcomes with the older patients in our study.     

Health- Related Quality of Life for Multiple Myeloma Patients with Bone Metastases in Indonesia: A Cross-Sectional Study

Objective: Multiple myeloma (MM) with bone metastases causes a skeletal-related event (SRE), and decreases health-related quality of life (HRQoL). HRQoL needs to be evaluated for health technology assessment (HTA). Furthermore, HRQoL is calculated as a health state utility and is used in the Markov Model for HTA. Therefore, this study aimed to describe the HRQoL of MM patients with bone metastases, using The EuroQol five-dimension five levels (EQ -5D-5L) in Indonesia. Methods: a cross-sectional, multicenter study for MM patients with bone metastases (aged over 18 years old) that consulted a physician between November 2018 - May 2019 was conducted. The calculated HRQoL illustrated the health state utility, which was assessed using the EQ-5D-5L questionnaire, with the Indonesian value set. In addition, Mann-Whitney analyses were performed to determine the difference in utility scores at different points within the Durie-Salmon staging system and skeletal condition. Results: in 93 patients who completed the questioner, pain was their major concern with prevalence of over 60% (all levels inclusive). Moreover, the mean utility of patients in stage II and III were 0.735 (SD = 0.205) and 0.383 (SD = 0.555), and those without SRE was 0.753 (SD = 0.213) while patients with SRE was 0.302 (SD = 0.562). Therefore, the lessened values were observed at stage III and SRE condition (p<0.05). Conclusion: MM patients with bone metastases have poor HRQoL, with pain as the most frequently reported challenge, which is associated with an advanced stage of MM and SRE event.     

Bone Health and Survival in Women With Multiple Myeloma

Background

Multiple myeloma (MM) is a disease of aging adults resulting in osteolytic and/or osteoporotic bone disease. Primary osteoporosis is also highly prevalent in aging adults and is associated with increased mortality. It is unknown how concurrent osteoporosis is associated with outcomes in patients who develop MM.

Assessment of Vulnerability Measures and Their Effect on Survival in a Real-Life Population of Multiple Myeloma Patients Registered at Marche Region Multiple Myeloma Registry

BackgroundMultiple myeloma is a typical disease of the elderly but how many and which patients can be considered ‘vulnerable’ and how this may affect patient outcome remain unsolved issues.Patients and MethodsData from 266 symptomatic MM patients registered at Marche MM registry from 2007 to 2010 were evaluated retrospectively. Vulnerability was defined as age > 75 years, PS (World Health Organization) ≥ 2, renal insufficiency (RI), bone fracture, cytopenias, and CCI score ≥ 1. Kaplan–Meier method and Cox regression were used to assess survival and associated factors. A vulnerability score (VS) incorporating significant vulnerability features was pursued to predict survival.ResultsThirty-eight percent of patients were older than 75 years, 39% had PS = 2-4, 35% had at least 2 cytopenias, 40% had bone fracture, 14% RI, and 51% had CCI score ≥ 1. Cox regression selected international staging system (ISS) = III (hazard ratio [HR] = 1.6; P = .033), PS = 2-4 (HR = 2.5; P = .007), and CCI = 1-3 (HR = 2.1; P = .028) as factors associated with a worse overall survival. A VS including PS and CCI predicted median survival of 27 months in the 63 patients having a VS = 2 (both PS = 2-4 and CCI = 1-3) versus not reached (NR) in the 203 patients with VS = 0-1 (HR = 4.0; P < .0001). In younger patients multivariate analysis selected ISS = III (HR = 5.2; P = .006) and VS = 2 (HR = 5.5; P = .024) as factors associated with shorter survival whereas only VS = 2 (HR = 3.5; P = .002) affected worse survival in elderly.ConclusionSuch VS proved to be a powerful prognostic factor for survival of MM patients and it might be useful to identify true vulnerable patients regardless of age.     

Hemostatic Abnormalities in Multiple Myeloma Patients

Background: Multiple myeloma (MM) is a neoplastic plasma cell disorder characterized by clonal proliferation of plasma cells in the bone marrow. Diverse hemostatic abnormalities have been reported in patients with myeloma which predispose to bleeding and also thrombosis. Methods: Complete blood count, biochemical parameters and parameters of hemostasis i.e. platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), factor VIII assay results, plasma fibrinogen, D-dimer and lupus anticoagulant, were assessed in 29 MM patients and 30 age matched controls. Results: The most frequent abnormal screening parameter was APTT. Of the six indicative of a bleeding tendency i.e. thrombocytopenia, prolonged PT, APTT, TT, reduced plasma fibrinogen and factor VIII, at least one was abnormal in 8 (27.6%) patients. Of the four prothrombotic markers, lupus anticoagulant, D-dimer, elevated factor VIII and plasma fibrinogen, one or more marker was present in 24 (82.7%). D-dimer was the most common prothrombotic marker, being elevated in 22 (75.9%) patients. One or more laboratory parameter of hemostasis was abnormal in all 29 (100%) patients. Though thrombotic complications are reported to be less frequent as compared to hemorrhagic manifestations, one or more marker of thrombosis was present in 24 (82.7%) patients. Conclusion: This study provided laboratory evidence of hemostatic dysfunction which may be associated with thrombotic or bleeding complications at diagnosis in all MM patients. Hence, screening for these abnormalities at the time of diagnosis should help improved prognosis in such cases.     

Prevalence and Survival Impact of Self-Reported Symptom and Psychological Distress Among Patients With Multiple Myeloma

BackgroundAdvances in the management of multiple myeloma (MM) have extended survival and reduced painful skeletal-related events. As MM is evolving toward a chronic disease, we sought to determine the prevalence of self-reported symptom burden and psychological distress, and to determine the association of distress with survival.MethodsThe CPASS-7 patient-reported outcome instrument was administered to a convenience sample of MM patients at 7 outpatient cancer centers.ResultsA total of 239 patients completed the CPASS-7 between September 2015 and October 2016%; 57% of respondents were male, and median age was 67 years. Forty-eight percent were concerned that they could not do the things they wanted to do, with 33% reporting decreased performance status. Financial toxicity concerns were self-reported by 44%, with family burdens noted in 24%. Although depression was reported by only 15%, 41% noted lack of pleasure. Pain was a concern in 36%. With a median follow-up of 316 days since CPASS-7 completion, 13% of patients had died. A high total distress score was noted in 57 (24%) and trended toward an association with a decreased survival rate compared to the 182 patients (76%) with a low total distress score (P = .066). The 6-month survival rates for patients with high and low distress scores were 86% and 96%, respectively, and 12-month survival rates were 76% and 87%, respectively.ConclusionDespite dramatic improvements in survival among patients with MM, symptom, financial, and psychosocial concerns continue to be major patient concerns. As MM becomes a chronic disease, additional attention to addressing these issues is required.     

Lack of Renal Recovery Predicts Poor Survival in Patients of Multiple Myeloma With Renal Impairment

BackgroundRenal impairment (RI) confers a poor prognosis in multiple myeloma. Reversibility of renal function is associated with improved survival in such patients. Patients in developing countries often present at an advanced stage and renal impairment is present in up to 40% of patients at diagnosis. We studied the renal outcome and survival of these patients with bortezomib-based induction therapy.Materials and MethodsIt was a single-center prospective study in a tertiary care multi-specialty institute in patients of newly diagnosed multiple myeloma (NDMM) who presented with RI from July 2018 to December 2019. The diagnosis of multiple myeloma was made based on IMWG14 criteria. All patients received bortezomib and or immunomodulatory drug-based triplet or quadruplet induction therapy. Hematological and renal outcomes were assessed as per IMWG 2016 criteria.ResultsAmong 216 consecutive patients of NDMM, RI was seen in 91 (42.2%) patients. The median age of 91 patients was 60 years. (range- 32-80 years). Light chain myeloma was seen in 26% (n = 24) of patients. The median estimated glomerular filtration rate (eGFR) was 15.36 mL/min (3.1-38 mL/min) and a majority of patients were in the advanced ISS stage. (ISS III = 85.7%). Thirty-six (39.5%) patients received hemodialysis at presentation. Renal response was seen in 67 (73%) patients and 20 (out of 36; 55%) became dialysis independent over a median time of 38 days (Range 15-160 days). At a median follow-up of 14.7 months, 30 (33%) patients had died, of which, 14 (15.4%) patients had early mortality (within 2 months of diagnosis). Presence of light chain myeloma and cast nephropathy (definite or probable) were identified as independent predictors of poor renal recovery on multivariate analysis. (HR = 2.841; 95% CI [1.471-5.486], P = .002 for light chain myeloma; HR = 1.859; 95% CI (1.087-3.180); P = .024 for cast nephropathy) Patients with low eGFR at presentation (<12.5 mL/min) were more likely to have persistent renal insufficiency. (HR-3.521; 95% CI (1.856-6.679), P = .000). Patients who attained sustained renal recovery had improved survival as compared to patients in whom renal function failed to improve. (median OS- not reached vs. 8.3 months, P = .000) Achievement of hematological response and independence from hemodialysis was associated with improved survival on multivariate analysis.ConclusionRenal impairment was reversible in almost three-fourths of NDMM patients. achievement of hematological response and hemodialysis independence were independent predictors of improved overall survival in NDMM patients with RI.     

Novel Treatment Approaches for Patients with Multiple Myeloma

Treatment options for patients with multiple myeloma are a rapidly progressing area of clinical and scientific development. The discovery of key signaling pathways needed for myeloma cell growth and proliferation has resulted in a plethora of new and different treatment options. Chief among these new agents are the proteasome inhibitor bortezomib and the immunomodulatory agents thalidomide and lenalidomide. Efficacy for these agents has been extensively studied in the relapsed and refractory states, and more recently in induction therapy. Impressive responses have been observed in the induction and relapsed disease states, completely changing the disease treatment paradigms. Building on these successes and strong preclinical work, other signal transduction inhibitors are being tested in phase I and phase II clinical trials. These include agents that target histone acetylation, farnesylation, heat shock proteins, and direct AKT-targeting agents. Additionally, monoclonal antibody targets are being developed in an effort to target the tumor cells extracellularly. Clinical trial development based on preclinically designed rational combinations and targets have the potential to rapidly translate these findings into meaningful clinical responses.     

Superior Survival in African American Patients Who Underwent Autologous Stem Cell Transplantation for Multiple Myeloma

Introduction/BackgroundAfrican American (AA) individuals have a twofold higher incidence of multiple myeloma (MM) compared with other racial groups. Outcomes are affected by factors such as disparate access to care as well as differences in disease biology.Patients and MethodsWe conducted a single-institution analysis to evaluate the effect of AA race on outcomes of MM patients who underwent autologous stem cell transplantation (ASCT) in the pre-novel and novel agent era.ResultsSixty-one (47%) patients were AA and 69 (53%) were non-AA. Overall, 78 (60%) patients received any novel agent before transplantation and 52 (40%) received only chemotherapy. More non-AA patients received initial induction with a proteasome inhibitor (40 [60%] vs. 17 [28%]; P = .0007), and were treated with post-ASCT maintenance therapy (28 [41%] vs. 14 [23%]; P = .04). Time from diagnosis to ASCT in AA patients was 10 (range, 4-144) versus 8 (range, 3-54) months in non-AA patients (P = .01). Despite this, treatment-free survival (TFS) was equivalent between the 2 groups (x vs. y). Furthermore, AA patients had greater median overall survival (OS) compared with non-AA patients (not reached vs. 108 months; P = .03) and significantly improved OS in multivariable Cox proportional hazards models (adjusted hazard ratio, 0.30; 95% confidence interval, 0.11-0.81; P = .017). Median OS, landmarked at the time of relapse, was improved in AA patients (not reached vs. 68 months for P = .05).ConclusionOur study showed with long follow-up, equivalent TFS after ASCT in AA and non-AA patients yet improved OS. Post relapse survival is improved in AA patients suggesting a better response to salvage therapy.     

Once-weekly Subcutaneous Administration of Bortezomib in Patients with Multiple Myeloma

In patients with multiple myeloma (MM), once-weekly intravenous injection or twice-weekly subcutaneousinjection (SC) of bortezomib has been proven to offer non-inferior efficacy to standard twice-weekly intravenousadministration, with an improved safety profile. However, whether once-weekly SC bortezomib can further reducethe incidence rate of peripheral neuropathy (PN) and not compromise the efficacy remains to be investigated.25 patients of MM treated with once-weekly SC bortezomib were reviewed in this study. The median treatmentcycles were 4 (range, 2-9 cycles). Complete response (CR) rate was 52%, ≥very good partial response (VGPR)rate was 72%, and ≥partial response (PR) rate was 84%. 1-year and 2-year PFS rate was 63.0% and 34.3%,respectively, and 2-year OS rate was 100%. Any grade of PN was reported in 9 patients (36.0%), with 7 patients(28.0%) had grade 1 PN, and 2 patients (8.0%) had grade 2 PN. No patients reported grade 3/4 PN in this cohort.In conclusion, once-weekly subcutaneous administration of bortezomib offers excellent efficacy with a furtherimproved safety profile, especially with regard to PN. It needs to be validated in future prospective randomizedtrials.