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Impact of age (< 60 vs. > 60 years) on the overall sur- vival.
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Age is a strong prognostic factor in multiple myeloma. The overall survival is shorter in patients older than 66 years, and even shorter in those older than 75 years. Whether age is also a prognostic parameter in patients younger than 66 years treated homogeneously with intensive approaches is unknown. To address this issue, we retrospectively anal...
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Background & objective:
Cytogenetic abnormalities in Multiple myeloma (MM) has emerged as the most important factor that determine the prognosis and survival. Fluorescence in situ hybridization (FISH) can detect a greater number of cytogenetic abnormalities as compared to conventional karyotyping and hence has become the standard test in determini...
Citations
... 14 Age is one of the most influential factors in this disease process as those older than 66 years have a significant decrease in overall survival compared to younger individuals. 15 Cytogenetic proliferation index, as well as other intrinsic properties like cellular characteristics of the tumor cells themselves, also play a significant role. 16 Hypoalbuminemia and AKI were both noted during lab evaluation of this patient; both of these are independent negative prognostic indicators for MM. ...
... The cut-off at 60 years old was based on a previous retrospective analysis looking at whether age could affect outcomes of transplanted myeloma patients (≤66 years). In that study, there was a higher risk of death in those ≥60 years old, mainly due to the higher percentage of ISS 2/3 stages [46]. By contrast, IMWG-defined HR FISH was not overrepresented in our patients ≥60 years of age [46][47][48][49]. ...
... In that study, there was a higher risk of death in those ≥60 years old, mainly due to the higher percentage of ISS 2/3 stages [46]. By contrast, IMWG-defined HR FISH was not overrepresented in our patients ≥60 years of age [46][47][48][49]. ...
In Hong Kong, newly diagnosed multiple myeloma (NDMM) receives bortezomib-based triplet induction. Upfront autologous stem cell transplant (ASCT) is offered to transplant eligible (TE) patients (NDMM ≤ 65 years of age), unless medically unfit (TE-unfit) or refused (TE-refused). Data was retrieved for 448 patients to assess outcomes. For the entire cohort, multivariate analysis showed that male gender (p = 0.006), international staging system (ISS) 3 (p = 0.003), high lactate dehydrogenase (LDH) (p = 7.6 × 10⁻⁷) were adverse predictors for overall survival (OS), while complete response/ near complete response (CR/nCR) post-induction (p = 2.7 × 10⁻⁵) and ASCT (p = 4.8 × 10⁻⁴) were favorable factors for OS. In TE group, upfront ASCT was conducted in 252 (76.1%). Failure to undergo ASCT in TE patients rendered an inferior OS (TE-unfit p = 1.06 × 10⁻⁸, TE-refused p = 0.002) and event free survival (EFS) (TE-unfit p = 0.00013, TE-refused p = 0.002). Among TE patients with ASCT, multivariate analysis showed that age ≥ 60 (p = 8.9 × 10⁻⁴), ISS 3 (p = 0.019) and high LDH (p = 2.6 × 10⁻⁴) were adverse factors for OS. In those with high-risk features (HR cytogenetics, ISS 3, R-ISS 3), ASCT appeared to mitigate their adverse impact. Our data reaffirmed the importance of ASCT. The poor survival inherent with refusal of ASCT should be recognized by clinicians. Finally, improved outcome with ASCT in those with high-risk features warrant further studies.
... Age is related to unfavorable outcomes [3,5,[19][20][21][22][23], and is considered a continuous variable, for which any cutoff to classify patients as young or old seems arbitrary. However, a reasonable criterion for transforming age into a categorical variable is practical in clinical application. ...
... However, a reasonable criterion for transforming age into a categorical variable is practical in clinical application. Until now, there is no consensus on the prognostic cut-off value of age [17,20,21,23]. Since the lower quartile and median value of age in this cohort is 51 and 59 years, respectively, and transplantation is only eligible to patients under 70 years old, which may exert a strong effect on survival, we stratified patients into ≤60, 61-70, ≥ 71 age subgroups as there was no survival difference between patients younger than 51-and 51-60 years old (data not shown). ...
Objective
Multiple myeloma is a highly heterogenous plasma cell malignancy, commonly seen in older patients. Age is one of the important prognostic factors. However, nearly all the prognostic staging systems are based on clinical trials, where patients were relatively fit and young. It is unknown how the presence of biochemical or cytogenetic prognostic factors and their risk weights changes with older age. To further investigate this question, we retrospectively analyzed the data from a consecutive cohort of patients treated with either bortezomib or thalidomide-based therapy.
Methods
This retrospective study was carried out on a cohort of 1125 newly diagnosed multiple myeloma patients, from January 2008 to December 2019. Patients received bortezomib or thalidomide-based induction and maintenance therapy. Patients accepted hematopoietic stem cell transplantation if eligible. Statistical analysis was conducted by Stata/MP 16.0 and SPSS 26.0.
Results
With age increasing, the proportion of patients with ISS 3, performance status score ≥2, and the incidence rate of gain(1q) significantly increased. We also found that ISS became less important in older patients. However, cytogenetic abnormalities exerted a consistently adverse impact on survival, both in young and old patients. Older patients had an inferior outcome than their young counterparts. All patients in our cohort benefitted more from bortezomib than thalidomide-based induction therapy, except for patients ≥71 years old.
Conclusions
ISS may lose prognostic value in patients ≥71 years old. Older patients had an inferior outcome and needed more effective and less toxic treatment.
Plain Language Summary
Multiple myeloma is a type of blood cancer commonly seen in older people. To treat this disease, genetic abnormality, the poor physical status of patients and the abundance of tumor cells are the main difficulties. We often draw these conclusions from clinical trials. However, clinical trials always enrolled relatively younger patients, so the presence and significance of these factors may vary from clinical trials to the real world. We conducted the study to find out the real risk in both young and old patients. We found that older patients were more likely to have anemia, poor nutritional status and renal function. We also found older patients had more risk of relapse, progression or death than young patients. Frail physical status is the key obstacle to treating older patients, and tumor burden no longer impacts the outcome of these people. Bortezomib is a powerful drug to treat this disease, but patients ≥71 years old had less benefit than younger ones. More studies should focus on older or frail patients as these patients need more effective and less toxic treatment.
... 8 A report from the French found a linear relationship between age and risk of death, with a 22% increase in mortality every 10 years. 75 In the era of novel agents (since 2000), improved OS for young MM compared to older counterparts was confirmed in thirteen retrospective analyses. 2 ,12 ,75 ,76 ,78 ,79 ,106 ,[122][123][124][125][126]12 ,106 ,122 ,123 were US-based, and the remainder were non-US. ...
... 75 In the era of novel agents (since 2000), improved OS for young MM compared to older counterparts was confirmed in thirteen retrospective analyses. 2 ,12 ,75 ,76 ,78 ,79 ,106 ,[122][123][124][125][126]12 ,106 ,122 ,123 were US-based, and the remainder were non-US. ...
... The cut-off at 60 years old was based on a previous retrospective analysis looking at whether age could affect outcomes of transplanted myeloma patients (≤ 66 years). In that study, there was a higher risk of death in those ≥ 60 years old, mainly due to the higher percentage of ISS 2/3 stages (40). By contrast, IMWG-de ned HR FISH was not over-represented in our patients ≥ 60 years of age (40)(41)(42)(43). ...
... In that study, there was a higher risk of death in those ≥ 60 years old, mainly due to the higher percentage of ISS 2/3 stages (40). By contrast, IMWG-de ned HR FISH was not over-represented in our patients ≥ 60 years of age (40)(41)(42)(43). ...
In Hong Kong, newly diagnosed multiple myeloma (NDMM) receives bortezomib-based triplet induction. Upfront autologous stem cell transplant (ASCT) is offered to transplant eligible (TE) patients (NDMM ≤65 years of age), unless medically unfit (TE-unfit) or refused (TE-refused). Data was retrieved for 448 patients to assess outcomes. For the entire cohort, multivariate analysis showed that male gender (p=0.011), international staging system (ISS) 3 (p=0.001), high lactate dehydrogenase (LDH) (p=0.000009) were adverse predictors for overall survival (OS), while complete response/ near complete response (CR/nCR) post-induction (p=0.000078) and ASCT (p=0.000478) were favorable factors for OS. In TE group, upfront ASCT was conducted in 252 (76.1%). Failure to undergo ASCT in TE patients rendered an inferior OS (TE-unfit p=1.06x10 ⁻⁸ , TE-refused p=0.002) and event free survival (EFS) (TE-unfit p=0.00013, TE-refused p=0.002). Among TE patients with ASCT, multivariate analysis showed that age≥60 (p=0.001), ISS 3 (p=0.004) and high LDH (p=0.000251) were adverse factors for OS. In those with high-risk features (HR cytogenetics, ISS3, R-ISS 3), ASCT appeared to mitigate their adverse impact. Our data reaffirmed the importance of ASCT. The poor survival inherent with refusal of ASCT should be recognized by clinicians. Finally, improved outcome with ASCT in those with high risk features warrant further studies.
... 10 Mortality in myeloma patients increases with age, with a drastic decline in survival rates after the age of 60 and the disease is uncommon below the age of 40 years and accounts for only 2% of all cases. 11 Bone pain and fatigue has been reported as the most common presenting symptoms in multiple myeloma patients. 6 The patients in our case series mainly presented with non-specific symptoms like easy fatigability, decreased appetite, bone pain and gum bleed. ...
Multiple myeloma is a plasma cell neoplasm characterized by abnormal proliferation of clonal cells in the bone marrow. Anaemia is generally the most common feature from hematologic aspect and bone pain being the other important symptom, but pancytopenia as the presenting feature is unusual. Here, we shared our experience of 3 cases with non- specific symptoms with pancytopenia which on through evaluation revealed our diagnosis. A hospital based observational descriptive case series was conducted wherein all the cases of multiple myeloma presenting with pancytopenia were included. Complete blood picture, peripheral smear, bone marrow aspirate and serum protein electrophoresis were reviewed and analysed. Pancytopenia as the initial presenting feature of multiple myeloma is an unique manifestation and diagnosing such cases require high degree of suspicion to avoid delay in the initiation of treatment.
... The median age at diagnosis is 70 years, and two-thirds of MM patients are more than 65 years old at first diagnosis 2 . Moreover, advanced age is associated with poor clinical prognosis 4,5 . Every year, about five of 100,000 people suffer from MM, and the overall prognosis has been relatively unfavorable until the application of new therapeutic strategies, such as proteasome inhibitor, immunomodulator and chimeric antigen receptor T-cell (CART) therapy. ...
Multiple myeloma (MM) is an incurable plasma cell hematological malignancy. Bortezomib has become the primary drug in the treatment of patients with MM. However, its negative effects, especially peripheral neuropathy (PN), affect the patients’ life quality and treatment continuity. However, there are few studies on baseline PN of MM, and little is known of the impact of baseline PN on the prognosis of MM patients. Therefore, we reviewed the clinical data of newly diagnosed MM patients in our center, explored the influencing factors of baseline PN, and evaluated PN’s influence on the prognosis of MM patients undergoing induction therapy with bortezomib. According to the inclusion and exclusion criteria, 155 MM patients were eligible for the retrospective study. The multivariate regression analysis, generalized additive fitting smooth curve, the receiver operating characteristic curve (ROC) and K-M curve were conducted in this study. We found that baseline PN in patients with MM was age-related; MM patients with baseline PN have more severe bortezomib induced PN (BiPN) during the four courses of induction therapy with bortezomib as the primary regimen and worse PN outcome after induction therapy. Additionally, the progression-free survival (PFS) and overall survival (OS) of MM patients with baseline PN were worse than those of the MM patients without baseline PN.
... Elderly patients are a highly diverse group, and the clinical course of MM patients is quite variable due to this diverse set, which makes the prognostic factors of MM complicated and diversi ed. Earlier reported risk factors for adverse prognosis include old age, low hemoglobin level, high marrow plasma cell ratio, hypercalcemia, and so on [4][5][6][7]. With the development of detection indicators, prognostic indicators for myeloma evaluation are constantly being updated. ...
Background: The level of thyroid hormones (TH) influences the prognosis of a wide range of diseases. Despite this, to date, there have been few studies that have evaluated the effect of TH levels on the prognosis of patients with multiple myeloma (MM). As a result, we investigated the effect of TH levels on survival in patients with MM.
Methods: TH levels and common adverse prognostic markers were compared in 124 newly diagnosed MM patients. To evaluate differences between categorical and continuous variables, Chi-Square test and Fisher's Exact test as well as Mann-Whitney U test were used. Kaplan-Meier test was used for survival analysis, and Cox proportional risk regression was used for univariate and multivariate analysis of overall survival (OS).
Results: A significant decrease in total thyroxine (TT4) and total triiodothyronine (TT3) was observed in patients with multiple myeloma (P <0.05) compared to healthy subjects. In multiple myeloma patients, the levels of TT4, TT3, free (F)T4, and FT3 in non-survivors were significantly lower than those in survivors (P <0.05), and TT4 levels were significantly positively correlated with hemoglobin and albumin levels (P <0.05). The Cox proportional hazard model revealed that age≥68 years (HR=0.463, 95%CI =0.226-0.900, P=0.036) and TT4≤67.66 nmol/L (HR=0.204, 95%CI=0.101-0.412, P <0.001) were an independent prognostic factors for OS in multiple myeloma patients (P <0.05).
Conclusions: Thyroid hormone levels, particularly TT4, may be an important predictor of poor prognosis in patients with MM.
... This is particularly true for risk status and response to induction therapy prior to ASCT. Interestingly, some parameters that have been historically associated with worse outcomes, such as older age or higher BMI, [20,21] were not significantly associated with inpatient ASCT or hospitalization during outpatient ASCT in our analysis. The reasons for this might be that doses of the chemo conditioning regimen are typically adjusted for age and have hence become more tolerable also for the elderly population. ...
High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) remains the standard of care for multiple myeloma (MM) patients. Although outpatient ASCT has been shown to be safe and feasible, the procedure is overall rare with most patients in the US undergoing inpatient ASCT. Furthermore, hospitalization rates for patients that undergo outpatient ASCT remain high. Adequate markers that predict hospitalization during outpatient ASCT are lacking, yet would be of great clinical value to select patients that are suited to outpatient ASCT. In this study we aimed to elucidate differences between planned outpatient and inpatient ASCT and further evaluated clinical characteristics that are significantly associated with hospitalization during planned outpatient hospitalization. Factors that were significantly associated with a planned inpatient ASCT included an advanced MM disease stage, worse performance status as well as non-Caucasian race, while low albumin levels and female gender were significantly associated with hospitalization during outpatient ASCT. The results of this analysis provide crucial knowledge of factors that are associated with planned inpatient ASCT and hospitalization during outpatient ASCT and could guide the treating physician in decision-making and further facilitate outpatient transplantation.
... Our study revealed the involvement of advanced age, low PLT level, and a high proportion of BPCs in poor prognosis in patients with MM in lieu of other studies. 5,6,8 Besides, low complement 4 levels were found to emerge as a risk for poor MM outcome as evidenced by the multivariate model. In addition, levels of C4 were negatively correlated with ISS stage (rs = −0.320) ...
Background
A cure for the heterogeneous hematological malignancy multiple myeloma (MM) is yet to be developed. To date, the early risk factors associated with poor outcomes in MM have not been fully elucidated. Studies have shown an aberrant complement system in patients with MM, but the precise association necessitates elucidation. Therefore, this study scrutinizes the correlation between serum complement level and the disease outcome of patients with MM.
Methods
A retrospective analysis of 72 patients with MM (new diagnosis) with complement C4 and C3 along with common laboratory indicators was done. The Pearson χ ² test and the Mann-Whitney U-test were done to evaluate categorical or binary variables and intergroup variance, respectively. Kaplan-Meier test and Cox proportional hazards regression were used for quantification of overall survival (OS) and univariate or multivariate analyses, respectively.
Results
The Cox proportional hazard model analysis unveiled the following: platelet ⩽115.5 × 10 ⁹ /L (hazard ratio [HR] = 5.82, 95% confidence interval [CI] = 2.522-13.436, P < .001), complement C4 ⩽0.095 g/L(HR = 3.642, 95% CI = 1.486-8.924, P = .005), age ⩾67 years (HR = 0.191, 95% CI = 0.078-0.47, P < .001), and bone marrow plasma cell percentage ⩾30.75% (HR = 0.171, 95% CI = 0.06-0.482, P = .001) can be used as independent predictors of OS. Of these, advanced age, low platelet level, and a high proportion of bone marrow plasma cells have been implicated in poor outcomes in patients with MM. Interestingly, a low complement 4 level can function as a new indicator of poor prognosis in patients with MM.
Conclusion
Low levels of C4 are indicative of a poor outcome in newly diagnosed patients with MM.
