Sex differences in outcomes in multiple myeloma.
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ABSTRACT:
SUBMITTER: Derman BA
PROVIDER: S-EPMC8182969 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundSex differences in the incidence and outcomes of several cancers are well established. Multiple myeloma (MM) is a malignant plasma cell dyscrasia accounting for 2% of all new cancer cases in the UK. There is a clear sex disparity in MM incidence, with 57% of cases in males and 43% in females. The mechanisms behind this are not well understood and the impact of sex on patient outcomes has not been thoroughly explored.Patients and methodsWe investigated the association of sex with baseline disease characteristics and outcome in 3894 patients recruited to the phase III UK NCRI Myeloma XI trial, in which treatment exposure to lenalidomide predominated.ResultsFemales were significantly more likely to have the molecular lesions t(14;16) and del(17p) and were more likely to meet the cytogenetic classification of high-risk (HiR) or ultra-high-risk disease (UHiR). There was no difference in progression-free survival (PFS) or overall survival (OS) between the sexes in the overall population.ConclusionOur data suggest that the genetic lesions involved in the initiation and progression of MM may be different between the sexes. Although females were more likely to have the poor prognosis lesions t(14;16) and del(17p), and were more likely to be assessed as having HiR or UHiR disease, this was not associated with reduced PFS or OS. In female patients the trial treatment may have been able to overcome some of the adverse effects of high-risk cytogenetic lesions. MicroAbstract Multiple myeloma (MM) is more common in males compared to females but the reasons behind this are not well understood and the impact of sex on patient outcomes is unclear. This study demonstrates fundamental differences in genetic lesions underlying the biology of MM between males and females. However, we found that progression-free survival and overall survival were the same in both sexes.
| S-EPMC8528179 | biostudies-literature
Project description:Findings on racial differences in survival in multiple myeloma (MM) have been inconclusive. We assessed differences in outcomes between White and Black individuals among 639 newly diagnosed MM patients in the MM Research Foundation CoMMpass registry with baseline cytogenetic data. Survival curves were constructed using the Kaplan-Meier method. Hazard ratios and 95% confidence intervals were derived from Cox proportional hazard regression models. Age, gender, and stage were similar between Whites (n = 526) and Blacks (n = 113). Blacks had inferior overall survival (OS) compared with Whites and were less likely to receive triplet therapies or frontline autologous stem cell transplant (ASCT). The following factors were significantly associated with inferior OS in multivariate analysis: higher international staging system (ISS) score, ≥1 or ≥2 high-risk cytogenetic abnormalities (HRCA), high-risk gene expression profile (GEP), and lack of ASCT. Multivariate analysis in the Black subset found that only lack of ASCT was significantly associated with inferior OS. The receipt of both triplet induction and ASCT only partly abrogated the effect of race on survival. HRCA did not track with survival in Blacks, emphasizing the need for race-specific risk prognostication schema to guide optimal MM therapy.
| S-EPMC7414120 | biostudies-literature
Project description: Not available
| S-EPMC9329432 | biostudies-literature
Project description:IntroductionData on kidney transplantation (KTx) outcomes of patients with multiple myeloma (MM) are very limited.MethodsWe investigated the outcomes of patients with MM who underwent KTx between 1994 and 2019.ResultsA total of 12 transplants from 11 patients were included. At the time of KTx, 6 were classified as having stringent complete response (CR), 2 as CR, 2 as very good partial response (VGPR), and 2 as partial response (PR). With a median follow-up of 40 (minimum-maximum, 5-92) months after KTx, hematologic progression occurred in 9 transplants (75%). There were 3 grafts (25%) that failed, and 5 patients (45.5%) experienced death with functioning allografts. Graft survival at 1 and 5 years was 82.5% and 66%, respectively. Progression-free survival (PFS) rates of the cohort at 1, 3, and 5 years were 83.3%, 55.6%, and 44.4%, respectively. The estimated median PFS of patients who received bortezomib at any time (pre-KTx and/or post-KTx) was not reached, whereas it was 24 months for those who never received bortezomib (P = 0.281). Overall survival (OS) rates of the cohort at 1, 3, and 5 years were 81.8%, 61.4%, and 61.4%, respectively. OS of patients who received bortezomib at any time was 87.5%, 72.9%, and 72.9%, and that for those who never received bortezomib was 66.7%, 33.3%, and 33.3% (P = 0.136). All deaths occurred owing to hematologic progression or treatment-related complications.ConclusionKidney transplant outcomes of patients with myeloma who received bortezomib before or after KTx seem to be more favorable. Nevertheless, relapse after KTx in MM is still common. More studies are needed to better determine who benefits from a KTx.
| S-EPMC9039485 | biostudies-literature
Project description:With increasing number of therapies available for the treatment of multiple myeloma, it is timely to examine the course of patients' journeys. We investigated patient characteristics, treatment durations and outcomes, and symptom burden across the treatment pathway in Belgium, France, Germany, Italy, Spain, Switzerland and the UK. In total, 435 physicians retrospectively reviewed 4997 patient charts. Profiles of patients diagnosed with multiple myeloma during the last 12 months were similar across countries; bone pain was the most common presentation. Median duration of first-line therapy was 6 months, followed by a median treatment-free interval of 10 months; both these decreased with increasing lines of therapy, as did time to progression. Depth of response, as assessed by the treating physician, also decreased with each additional line of therapy: 74% of patients achieved at least a very good partial response at first line, compared with only 11% at fifth line. Deeper responses were associated with longer time to progression, although these were physician-judged. Toxicities and co-morbidities increased with later treatment lines, and were more likely to have led to discontinuation of treatment. These real-world data provide an insight into patient outcomes and treatment decisions being made in clinical practice.
| S-EPMC5096152 | biostudies-literature
Project description:Background The study investigated sex differences in cognitive outcomes at 90 days after first-ever stroke using data from a population-based sample. Methods and Results The study sample consisted of 1227 participants from the 2009-2016 Brain Attack Surveillance in Corpus Christi project (south Texas, United States) who had first-ever ischemic stroke or intracerebral hemorrhage and survived 90 days after stroke. Poststroke cognitive function was assessed by the Modified Mini-Mental State Examination (3MSE) (range: 0-100; dementia: <78). The associations of sex with dichotomized and continuous outcomes were examined using logistic regression and tobit regression, respectively. Inverse probability weighting and multiple imputation were used to deal with missing data. The study sample was evenly distributed by sex, and primarily composed of Mexican Americans (59.1%) and non-Hispanic whites (34.1%). Women scored 2.96 points worse on the 3MSE than men at 90 days poststroke (95% CI, -3.99 to -1.93). The prevalence of dementia was 27.6% for men (95% CI, 23.5%-31.6%) and 35.6% for women (95% CI, 31.5%-39.7%), and the unadjusted odds ratio (OR) of dementia comparing women with men was 1.45 (95% CI, 1.24-1.69). The association was attenuated after adjustment for sociodemographic, stroke, and prestroke characteristics (OR, 0.82; 95% CI, 0.61-1.09). Conclusions Women had worse cognitive outcomes than men at 90 days poststroke. The differences were attributable to sociodemographic and prestroke characteristics, especially widowhood status. Potential mechanisms linking widowhood to dementia in the acute poststroke stage warrant further investigation to inform interventions addressing the unique care needs of women stroke survivors with dementia and cognitive dysfunction.
| S-EPMC7660722 | biostudies-literature
Project description:Background and objectivesLittle is known of the potential sex and age differences in the MS prodrome. We investigated sex and age differences in healthcare utilization during the MS prodrome.MethodsThis was a population-based matched cohort study linking administrative and clinical data from British Columbia, Canada (population = 5 million). MS cases in the 5 years preceding a first demyelinating event ("administrative cohort;" n = 6,863) or MS symptom onset ("clinical cohort;" n = 966) were compared to age-, sex- and geographically-matched controls (n = 31,865/4,534). Negative binomial and modified Poisson models were used to compare the rates of physician visits and hospitalizations per international classification of diseases chapter, and prescriptions filled per drug class, between MS cases and controls across sex and age-groups (< 30, 30-49, ≥50 years).ResultsIn the administrative cohort, males with MS had a higher relative rate for genitourinary-related visits (males: adjusted Rate Ratio (aRR) = 1.65, females: aRR = 1.19, likelihood ratio test P = 0.02) and antivertigo prescriptions (males: aRR = 4.72, females: aRR = 3.01 P < 0.01). Injury and infection-related hospitalizations were relatively more frequent for ≥50-year-olds (injuries < 30/30-49/≥50: aRR = 1.16/1.39/2.12, P < 0.01; infections 30-49/≥50: aRR = 1.43/2.72, P = 0.03), while sensory-related visits and cardiovascular prescriptions were relatively more common in younger persons (sensory 30-49/≥50: aRR = 1.67/1.45, P = 0.03; cardiovascular < 30/30-49/≥50: aRR = 1.56/1.39/1.18, P < 0.01). General practitioner visits were relatively more frequent in males (males: aRR = 1.63, females: aRR = 1.40, P < 0.01) and ≥50-year-olds (< 30/≥50: aRR = 1.32/1.55, P = 0.02), while differences in ophthalmologist visits were disproportionally larger among younger persons, < 50-years-old (< 30/30-49/≥50: aRR = 2.25/2.20/1.55, P < 0.01). None of the sex and age-related differences in the smaller clinical cohort reached significance (P ≥ 0.05).DiscussionSex and age-specific differences in healthcare use were observed in the 5 years before MS onset. Findings demonstrate fundamental heterogeneity in the MS prodromal presentation.
| S-EPMC9668896 | biostudies-literature
Project description:Since the introduction of the proteasome inhibitor bortezomib and the immunomodulatory drugs (IMiDs) thalidomide and lenalidomide, more patients with multiple myeloma are achieving deep, durable responses and disease control, and are living longer. These improvements have afforded more robust analyses of the relationship between response and survival. Generally, these studies have demonstrated that improvements in the quality of response across all stages of treatment are associated with better disease control and longer survival. Thus, achievement of maximal response should be strongly considered, particularly in the frontline setting, but must also be balanced with tolerability, quality of life and patient preferences. In select patients, achievement of a lesser response may be adequate to prolong survival, and attempts to treat these patients to a deeper response may place them at unnecessary risk without significant benefit. Maintenance therapy has been shown to improve the quality of response and disease control and, in some studies, survival. Studies support maintenance therapy for high-risk patients as a standard of care, and there are emerging data supporting maintenance therapy in standard-risk patients to improve progression-free and possibly overall survival. Multidrug regimens combining a proteasome inhibitor and an IMiD have shown exceptional response outcomes with acceptable increases in toxicity in both the frontline and salvage settings, and are becoming a standard treatment approach. Moving forward, the use of immunophenotypic and molecular response criteria will be essential in better understanding the impact of highly active and continuous treatment regimens across myeloma patient populations. Future translational studies will help to develop antimyeloma agents to their fullest potential. The introduction of novel targeted therapies, including the IMiD pomalidomide and the proteasome inhibitors carfilzomib and ixazomib (MLN9708), will provide greater options to individualize treatment and help patients achieve a clinically meaningful response.
| S-EPMC3918869 | biostudies-literature
Project description:Risk stratification of multiple myeloma (MM) at diagnosis is critical. We examined the ability of hematopoietic indices including mean corpuscular volume (MCV), hemoglobin (Hgb), and platelet (Plt) to predict outcomes. This was a retrospective study of patients treated at Mayo Clinic between January 2004 and April 2018. We incorporated three variables (Hgb < 10 g/dL, Plt < 150 × 109 /L, and MCV > 96 fL), assigning a score of 1 to each. We identified 1540 newly diagnosed MM patients, of whom 707 (46%) had a score of 0, 513 (33%) had a score of 1, 260 (17%) had a score of 2, and 60 (4%) had a score of 3. The score risk stratified patients into four groups with differing survivals. The median PFS was 32.3 months for score 0, 24.8 months for score 1, 21.7 months for score 2, and 18.3 months for score 3, for P < .001. The median OS was 80.7 months for score 0, 59.9 months for score 1, 51.7 months for score 2, and 31.3 months for score 3, P < .0001. Predictors of OS on the multivariable analysis were age ≥ 65 (HR, 1.93; P < .0001), R-ISS stage (1-2 vs 3) (HR, 0.48; P < .0001), and hematopoietic score (0-2 vs 3) (HR, 0.51; P = .006). A hematopoietic score can predict survival in newly diagnosed myeloma patients.
| S-EPMC7377299 | biostudies-literature