Real-world multiple myeloma risk factors and outcomes by non-Hispanic Black/African American and non-Hispanic White race/ethnicity in the United States.

Examination of the impact of race and ethnicity on multiple myeloma (MM) outcomes has yielded inconsistent results. This retrospective, real-world (RW) study describes patient, disease, and treatment characteristics (and associations with survival outcomes) among newly diagnosed MM patients of non-Hispanic (NH) Black/African American (AA) and NH White race/ethnicity in the United States. We included patients from the nationwide Flatiron Health electronic health record-derived de-identified database who initiated first line of therapy (LOT) for MM between January 1, 2016 and March 31, 2022. Of 4,614 patients in our study cohort, 23.3% were NH Black/AA. Non-Hispanic Black/AA patients were younger than NH White patients at diagnosis (median 68 vs 71 years) and more likely to be female (53.4% vs 43.5%). Rates of high-risk cytogenetics and 1q21+ were similar between races/ethnicities. The most common primary regimen used was lenalidomide-bortezomib-dexamethasone (50.1% of NH Black/AA and 48.1% of NH White patients). Receipt of stem cell transplantation during first LOT was less common among NH Black/AA (16.5%) than NH White (21.9%) patients. Unadjusted RW progression-free survival (rwPFS) and overall survival (rwOS) were similar between races/ethnicities. After multivariable adjustment, NH Black/AA race/ethnicity was associated with slightly inferior rwPFS (hazard ratio [HR] 1.13; 95% CI 1.01-1.27). The difference in rwOS (HR 1.12; 95% CI 0.98-1.28) was not statistically significant. In general, associations between risk factors for rwPFS and rwOS were consistent between races/ethnicities. Findings from this analysis help to inform clinicians about the impact of race/ethnicity on MM treatment paradigms and outcomes in the United States.

Real-world multiple myeloma front-line treatment and outcomes by transplant in the United States.

Stem cell transplantation (SCT) has been an integral treatment modality for multiple myeloma (MM) for decades. However, as standard-of-care therapies have improved, the benefit of SCT has been repeatedly called into question. This retrospective study evaluated the association between SCT in the first line of therapy (LOT) and outcomes for patients with newly diagnosed multiple myeloma (NDMM) in the United States. We included patients from a de-identified electronic health record-derived database who initiated front-line MM therapy between January 1, 2016, and January 31, 2022. Overall, 18.8% (1127 of 5996 patients) received SCT in the first LOT. Multivariable-adjusted Cox proportional hazards models, in which SCT was modeled as time varying, revealed longer real-world progression-free survival (rwPFS; hazard ratio [HR] 0.49; 95% confidence interval [CI] 0.43-0.57) and real-world overall survival (rwOS; HR 0.47; 95% CI 0.39-0.56) for patients who received SCT in the first LOT. The degree of rwPFS and rwOS benefit imparted by SCT was consistent across all subgroups examined, including patients aged ≥75 years, women, non-Hispanic Black/African American patients, those with renal impairment, and those with high-risk cytogenetics. Findings from this analysis of real-world patients with NDMM suggest that SCT remains an important standard of care in the era of novel therapies.

Safety of Aflibercept in Metastatic Colorectal Cancer: A Literature Review and Expert Perspective on Clinical and Real-World Data.

BACKGROUND: Metastatic colorectal cancer (mCRC) represents a substantial health burden globally and an increasing challenge in Asian countries. Treatment options include chemotherapy plus a vascular endothelial growth factor (VEGF) inhibitor (such as bevacizumab, aflibercept or ramucirumab), or anti-epidermal growth factor receptor (EGFR) therapies. Aflibercept, a recombinant fusion protein, has been approved for treatment of mCRC in combination with FOLFIRI for patients whose disease progresses during or after treatment with an oxaliplatin-containing regimen, based on its efficacy and tolerability profile in clinical trials. This report aims to provide an overview of both clinical and real-world evidence and experience on the use of aflibercept in routine clinical practice, with a focus on European, American and Asian populations. METHODS: A literature search was conducted in PubMed (on 28th February 2019) using the search terms ("aflibercept") and ("Colorectal"OR"CRC") to identify publications containing information on aflibercept-containing regimens. RESULTS: The adverse events (AE) profile was similar between geographical locations. Across trials, real-world and retrospective studies, grade ≥ 3 hypertension and proteinuria were amongst the most frequently reported AEs. CONCLUSIONS: The safety profile of aflibercept is generally manageable and comparable across various geographic locations.

Long-term effectiveness and safety of metreleptin in the treatment of patients with partial lipodystrophy.

PURPOSE: To evaluate the effects of metreleptin in patients with partial lipodystrophy (PL). METHODS: Patients aged ≥ 6 months with PL, circulating leptin < 12.0 ng/mL, and diabetes mellitus, insulin resistance, or hypertriglyceridemia received metreleptin doses (once or twice daily) titrated to a mean of 0.124 mg/kg/day. Changes from baseline to month 12 in glycated hemoglobin (HbA1c) and fasting serum triglycerides (TGs; co-primary endpoints), fasting plasma glucose (FPG), and liver volume were evaluated. Additional assessments included the proportions of patients achieving target decreases in HbA1c or fasting TGs at month 12, long-term treatment effects, and treatment-emergent adverse events (TEAEs). RESULTS: Significant (p < 0.05) reductions in HbA1c (-0.6%), fasting TGs (-20.8%), FPG (-1.2 mmol/L), and liver volume (-13.4%) were observed in the overall PL population at month 12. In a subgroup of patients with baseline HbA1c ≥ 6.5% or TGs ≥ 5.65 mmol/L, significant (p < 0.05) reductions were seen in HbA1c (-0.9%), fasting TGs (-37.4%), FPG (-1.9 mmol/L), and liver volume (-12.4%). In this subgroup, 67.9% of patients had a ≥ 1% decrease in HbA1c or ≥ 30% decrease in fasting TGs, and 42.9% had a ≥ 2% decrease in HbA1c or ≥ 40% decrease in fasting TGs. Long-term treatment in this subgroup led to significant (p < 0.05) reductions at months 12, 24, and 36 in HbA1c, fasting TGs, and FPG. Metreleptin was well tolerated with no unexpected safety signals. The most common TEAEs were abdominal pain, hypoglycemia, and nausea. CONCLUSIONS: In patients with PL, treatment with metreleptin was well tolerated and resulted in improvements in glycemic control, hypertriglyceridemia, and liver volume.

Long-term effectiveness and safety of metreleptin in the treatment of patients with generalized lipodystrophy.

PURPOSE: The purpose of this study is to summarize the effectiveness and safety of metreleptin in patients with congenital or acquired generalized lipodystrophy. METHODS: Patients (n = 66) aged ≥6 months had lipodystrophy, low circulating leptin, and ≥1 metabolic abnormality (diabetes mellitus, insulin resistance, or hypertriglyceridemia). Metreleptin dose (once or twice daily) was titrated to a mean dose of 0.10 mg/kg/day with a maximum of 0.24 mg/kg/day. Means and changes from baseline to month 12 were assessed for glycated hemoglobin (HbA1c), fasting triglycerides (TGs), and fasting plasma glucose (FPG). Additional assessments included the proportions of patients achieving target decreases in HbA1c or fasting TGs at months 4, 12, and 36, medication changes, and estimates of liver size. Treatment-emergent adverse events (TEAEs) were recorded. RESULTS: Significant mean reductions from baseline were seen at month 12 for HbA1c (-2.2%, n = 59) and FPG (-3.0 mmol/L, n = 59) and mean percent change in fasting TGs (-32.1%, n = 57) (all p ≤ 0.001). Reductions from baseline over time in these parameters were also significant at month 36 (all p < 0.001, n = 14). At month 4, 34.8% of patients had a ≥1% reduction in HbA1c and 62.5% had a ≥30% reduction in fasting TGs; at month 12, 80% of patients had a ≥1% decrease in HbA1c or ≥30% decrease in TGs, and 66% had a decrease of ≥2% in HbA1c or ≥40% decrease in TGs. Of those on medications, 41%, 22%, and 24% discontinued insulin, oral antidiabetic medications, or lipid-lowering medications, respectively. Mean decrease in liver volume at month 12 was 33.8% (p < 0.001, n = 12). Most TEAEs were of mild/moderate severity. CONCLUSIONS: In patients with generalized lipodystrophy, long-term treatment with metreleptin was well tolerated and resulted in sustained improvements in hypertriglyceridemia, glycemic control, and liver volume.

Relationship of cravings with weight loss and hunger. Results from a 6 month worksite weight loss intervention.

We examined the association of food cravings with weight loss and eating behaviors in a lifestyle intervention for weight loss in worksites. This research was part of a randomized controlled trial of a 6-month weight loss intervention versus a wait-listed control in 4 Massachusetts worksites. The intervention emphasized reducing energy intake by adherence to portion-controlled menu suggestions, and assessments were obtained in 95 participants at baseline and 6 months including non-fasting body weight, food cravings (Craving Inventory and Food Craving Questionnaire for state and trait) and the eating behavior constructs restraint, disinhibition and hunger (Eating Inventory). There were statistically significant reductions in all craving variables in the intervention group compared to the controls. Within the intervention group, changes in craving-trait were significantly associated with weight loss after controlling for baseline weight, age, gender and worksite. However, in a multivariate model with craving-trait and eating behaviors (restraint, disinhibition and hunger), hunger was the only significant predictor of weight change. In contrast to some previous reports of increased food cravings with weight loss in lifestyle interventions, this study observed a broad reduction in cravings associated with weight loss. In addition, greater reductions in craving-trait were associated with greater weight change, but craving-trait was not a significant independent correlate of weight change when hunger was included in statistical models. Studies are needed to examine the effectiveness of hunger suppressing versus craving-suppressing strategies in lifestyle interventions for obesity.

Eating behaviors as predictors of weight loss in a 6 month weight loss intervention.

OBJECTIVE: To examine associations between eating behavior constructs and weight loss (WL) in a 6-month WL intervention in worksites. DESIGN AND METHODS: A cluster-randomized controlled trial of a group behavioral WL intervention versus wait-listed control was conducted at four worksites. Measures included body weight and the eating behavior constructs restraint, disinhibition, hunger, and their sub-constructs. Rates of intervention meeting attendance and weight self-monitoring were also quantified. RESULTS: WL was greater in intervention participants than controls (ΔI = -8.1±6.8 kg, ΔC = +0.9±3.6 kg, P<0.001). Between-group analyses showed that the intervention was associated with increased restraint (ΔI = 5.43±4.25, ΔC = 0.29±3.80, P<0.001), decreased disinhibition (ΔI = -2.5±3.63, ΔC = 0.66±1.85, P < 0.001) and decreased hunger (ΔI = -2.79±3.13, ΔC = 0.56±2.63, P < 0.001), and changes in all eating behavior subscales. Greater WL in intervention participants was correlated with higher baseline hunger (r = -0.25, P = 0.03), increased restraint (r = -0.35, P=0.001), decreased disinhibition (r = 0.26, P = 0.02), and decreased hunger (r = 0.36, P = 0.001). However, in a multiple regression model including rates of meeting attendance and self-monitoring, decreased hunger was the only eating behavior change that predicted weight loss (R(2) =0.57, P<0.001). CONCLUSION: Decreased hunger was the strongest predictor of WL in this intervention with relatively high mean WL. Further studies are needed to confirm the central role of hunger management in successful WL.

Lifestyle intervention reduces body weight and improves cardiometabolic risk factors in worksites.

BACKGROUND: Worksites are potentially effective locations for obesity control because they provide opportunities for group intervention and social support. Studies are needed to identify effective interventions in these settings. OBJECTIVE: We examined the effects of a multicomponent lifestyle intervention on weight loss and prevention of regain in 4 worksites (2 intervention and 2 control sites). DESIGN: Overweight and obese employees (n = 133) enrolled in this pilot worksite-randomized controlled trial with a 0-6-mo weight-loss phase and a 6-12-mo structured weight-maintenance phase. The intervention combined recommendations to consume a reduced-energy, low-glycemic load, high-fiber diet with behavioral change education. Outcome measurements included changes in body weight and cardiometabolic risk factors. RESULTS: The mean ± SEM weight loss was substantial in intervention participants, whereas control subjects gained weight (-8.0 ± 0.7 compared with +0.9 ± 0.5 kg, respectively; P < 0.001), and 89% of participants completed the weight-loss phase. Intervention effects were not significant at the 0.05 level but would have been at the 0.10 level (P = 0.08) in a mixed model in which the worksite nested within group was a random factor. There were also significant improvements in cardiometabolic risk factors in intervention compared with control subjects regarding fasting total cholesterol, glucose, systolic blood pressure, and diastolic blood pressure (P ≤ 0.02 for each). No significant weight regain was observed in participants who enrolled in the structured weight-maintenance program (0.5 ± 0.7 kg; P = 0.65), and overweight and obese employees in intervention worksites who were not enrolled in the weight-loss program lost weight compared with subjects in control worksites (-1.3 ± 0.5 compared with +0.7 ± 0.2 kg, respectively; P = 0.02). CONCLUSION: Worksites can be effective for achieving clinically important reductions in body weight and improved cardiometabolic risk factors. This trial was registered at clinicaltrials.gov as NCT01470222.

A weight-loss diet including coffee-derived mannooligosaccharides enhances adipose tissue loss in overweight men but not women.

Mannooligosaccharides (MOS), extracted from coffee, have been shown to promote a decrease in body fat when consumed as part of free-living, weight-maintaining diets. Our objective was to determine if MOS consumption (4 g/day), in conjunction with a weight-loss diet, would lead to greater reductions in adipose tissue compartments than placebo. We conducted a double-blind, placebo-controlled weight-loss study in which 60 overweight men and women consumed study beverages and received weekly group counseling for 12 weeks. Weight and blood pressure were measured weekly, and adipose tissue distribution was assessed at baseline and at end point using magnetic resonance imaging. A total of 54 subjects completed the study. Men consuming the MOS beverage had greater loss of body weight than men consuming the Placebo beverage (-6.0 ± 0.6% vs. -2.3 ± 0.5%, respectively, P < 0.05). Men consuming the MOS beverage also had reductions in total body volume (P < 0.0001), total (P < 0.0001), subcutaneous (P < 0.0001), and visceral (P < 0.05) adipose tissue that were greater than changes observed in those consuming the Placebo beverage. In women, changes in body weight and adipose tissue compartments were not different between groups. Adding coffee-derived MOS to a weight-loss diet enhanced both weight and adipose tissue losses in men, suggesting a potential functional use of MOS for weight management and improvement in adipose tissue distribution. More studies are needed to investigate the apparent gender difference in response to MOS consumption.

Coffee mannooligosaccharides, consumed as part of a free-living, weight-maintaining diet, increase the proportional reduction in body volume in overweight men.

Clinical studies have shown that the consumption of coffee mannooligosaccharides (MOS) decreases body fat, suggesting that MOS consumption may be useful for weight management. This study was undertaken to determine whether consumption of coffee MOS improves body composition when consumed as part of a weight-maintaining diet. In this double-blind, randomized, placebo-controlled study, 54 men and women, age 19-65 y and with BMI of 27-33 kg/m(2), consumed study beverages twice daily, for 12 wk. Beverages were identical except for the presence (MOS group) or absence (placebo group) of MOS (4 g/d). Body composition was assessed at baseline and endpoint using magnetic resonance imaging (MRI). Body weight, blood pressure, and assessments of feelings of appetite and satiety were taken weekly. Fifty men and women completed both baseline and endpoint MRI scans. There was a significant beverage x time interaction on total body volume (P = 0.026), total adipose tissue (TAT) (P = 0.046), and total subcutaneous adipose tissue (P = 0.032) in men but not women. Men consuming the MOS beverage had a greater percent change in total body volume (P = 0.043) and tended to have greater percent changes in subcutaneous (P = 0.069) and TAT (P = 0.098) compared with the placebo group. Consumption of a MOS-containing beverage, as part of a free-living weight-maintaining diet, leads to reductions in total body volume, relative to placebo, in men. More research is needed to further investigate the mechanism by which MOS may act to improve body composition and to elucidate the influence of gender.

Physical and psychological outcomes among women in a telephone-based exercise intervention during adjuvant therapy for early stage breast cancer.

BACKGROUND: Many women gain weight after breast cancer diagnosis. Weight gain has been associated with poor quality of life (QOL), dissatisfaction with one's body, increased risk of postoperative complications, and possibly even an increased risk of breast cancer recurrence. Studies have suggested that decreases in physical activity during treatment may contribute to weight gain in breast cancer patients. METHODS: In this single-arm pilot study, 41 sedentary women with early stage breast cancer participated in a 12-week, moderate-intensity aerobic exercise intervention during adjuvant chemotherapy and/or radiation. The target exercise goal was 150 minutes of activity/week. Participants underwent evaluation of exercise behaviors, fitness, and psychological and anthropometric measures at baseline and after the 12-week intervention. RESULTS: Most participants were premenopausal, and 80% were treated with intensive chemotherapy regimens that included both an anthracycline and a taxane. In the 34 patients for whom baseline and week 12 measures were available, weekly exercise increased from 13 minutes to 116 minutes at week 12 (p < 0.001). Cardiorespiratory fitness and QOL improved significantly (p < 0.003 and p = 0.001, respectively), and there was a trend toward improvements in fatigue (p = 0.08). Participants also avoided weight gain and increases in body fat over the course of the 12-week protocol. CONCLUSIONS: Women participating in a home-based exercise intervention during adjuvant therapy significantly increased activity and avoided weight gain, which has been associated with poor QOL and cancer outcomes in early stage breast cancer.

Impact of a mixed strength and endurance exercise intervention on levels of adiponectin, high molecular weight adiponectin and leptin in breast cancer survivors.

UNLABELLED: Evidence suggests that exercise affects breast cancer risk and outcomes, but little is known about the mechanisms through which this effect may be mediated. This study examines the impact of exercise upon levels of adiponectin, high molecular weight adiponectin (HMWA), and leptin in breast cancer survivors. METHODS: One hundred and one sedentary, overweight breast cancer survivors were randomized to a 16-week exercise intervention or usual care control group. Anthropometric measurements were taken and fasting levels of adiponectin, HMWA and leptin were collected at baseline and 16 weeks. RESULTS: Baseline and week-16 measurements were available for 81 patients. The exercise group experienced a significant decrease in hip measurements, with no change in weight or body composition. There were no significant changes in adiponectin, HMWA, or leptin in either group. Modeling analyses demonstrated a significant inverse relationship between changes in leptin and adiponectin, but no relationship between changes in BMI, waist or hip circumference, or body fat percentage and change in leptin or adiponectin. CONCLUSIONS: This study did not demonstrate a significant change in adipocytokine levels in breast cancer survivors participating in an exercise intervention, suggesting that further work is needed to explore the mechanisms through which exercise may impact breast cancer.

Impact of a mixed strength and endurance exercise intervention on insulin levels in breast cancer survivors.

PURPOSE: Accumulating data suggest that exercise may affect breast cancer risk and outcomes. Studies have demonstrated that high levels of insulin, often seen in sedentary individuals, are associated with increased risk of breast cancer recurrence and death. We sought to analyze whether exercise lowered insulin concentrations in breast cancer survivors. METHODS: One hundred one sedentary, overweight breast cancer survivors were randomly assigned either to a 16-week cardiovascular and strength training exercise intervention or to a usual care control group. Fasting insulin and glucose levels, weight, body composition, and circumference at the waist and hip were collected at baseline and 16 weeks. RESULTS: Baseline and 16-week measurements were available for 82 patients. Fasting insulin concentrations decreased by an average of 2.86 microU/mL in the exercise group (P = .03), with no significant change in the control group (decrease of 0.27 microU/mL, P = .65). The change in insulin levels in the exercise group seemed greater than the change in controls, but the comparison did not reach statistical significance (P = .07). There was a trend toward improvement in insulin resistance in the exercise group (P = .09) but no change in fasting glucose levels. The exercise group also experienced a significant decrease in hip measurements, with no change in weight or body composition. CONCLUSION: Participation in an exercise intervention was associated with a significant decrease in insulin levels and hip circumference in breast cancer survivors. The relationship between physical activity and breast cancer prognosis may be mediated, in part, through changes in insulin levels and/or changes in body fat or fat deposition.