KarMMa-RW: comparison of idecabtagene vicleucel with real-world outcomes in relapsed and refractory multiple myeloma.

Patients with relapsed and refractory multiple myeloma (RRMM) who are triple-class exposed (to an immunomodulatory agent, proteasome inhibitor, and anti-CD38 antibody) have limited treatment options and there is no standard of care. Idecabtagene vicleucel (ide-cel, bb2121), a BCMA-directed CAR T-cell therapy, demonstrated efficacy in triple-class exposed RRMM patients in the KarMMa trial (NCT03361748). In this retrospective study (KarMMa-RW), patient-level data from triple-class exposed RRMM patients were merged into a single data model and compared with KarMMa using trimmed stabilized inverse probability of treatment weighting. Endpoints included overall response rate (ORR; primary), rate of very good partial response or better (≥VGPR), progression-free survival (PFS), and overall survival (OS). Of 1949 real-world triple-class exposed RRMM patients, 190 received subsequent (index) line of therapy and met KarMMa eligibility criteria (Eligible RRMM cohort). With a median follow-up of 13.3 months in KarMMa and 10.2 months in Eligible RRMM, ORR, and ≥VGPR were significantly improved in KarMMa versus Eligible RRMM (ORR, 76.4% vs 32.2%; ≥VGPR, 57.9% vs 13.7%; both P < 0.0001) as were PFS (11.6 vs 3.5 months; P = 0.0004) and OS (20.2 vs 14.7 months; P = 0.0006). This study demonstrated that ide-cel significantly improved responses and survival compared with currently available therapies in triple-class exposed RRMM.

Can Assessment of Disease Burden Prior to Changes in Initial COPD Maintenance Treatment Provide Insight into Remaining Unmet Needs? A Retrospective Database Study in UK Primary Care.

This retrospective cohort study aimed to assess treatment patterns over 24 months amongst patients with chronic obstructive pulmonary disease (COPD), initiating a new COPD maintenance treatment, and to understand clinical indicators of treatment change. Patients included in the study initiated a long-acting ß2-agonist (LABA), a long-acting muscarinic antagonist (LAMA), or a combination of LABA and an inhaled corticosteroid (ICS/LABA) between January 1, 2009, and November 30, 2013, as recorded in the United Kingdom Clinical Practice Research Datalink (UK CPRD). Treatment modifications (switching or adding maintenance treatments) over 24 months were assessed, and patient characteristics, disease burden, medication and healthcare resource use during the 30 days before treatment modification were evaluated. The cohort comprised 17,258 patients [LABA (8%), LAMA (39%) and ICS/LABA (54%)] with similar age, body mass index and dyspnoea distribution. LABA users were more likely than LAMA users to add a maintenance therapy. Distinct patterns of treatment augmentations were noted, whereby LABA users typically received dual therapy before moving to triple therapy, while LAMA users moved to triple therapy by directly adding an ICS/LABA. Exacerbation events immediately prior to treatment change were not frequently recorded; however, the need for rescue short-acting medication and assessment of dyspnoea in the 30 days prior to the treatment change suggest that dyspnoea is a remaining unmet need driving therapy change.

Relationship between blood eosinophils and clinical characteristics in a cross-sectional study of a US population-based COPD cohort.

BACKGROUND: Current evidence suggests that blood eosinophil levels (Eos) are associated with chronic obstructive pulmonary disease (COPD) treatment response and natural history. This analysis investigated the relationship between Eos levels and clinical characteristics in a representative cohort of US subjects with spirometry-defined COPD. METHODS: Cross-sectional data from the National Health And Nutrition Examination Survey (NHANES 2007-2010) of subjects ≥ 40 years with spirometry-defined COPD and Eos data (n = 948) were analyzed. Differences in clinical characteristics by Eos level (≤ 2%, > 2%) were compared using chi-square tests. Characteristics associated with Eos > 2% were identified using multivariate logistic regression modeling. Characteristics associated with Eos >2% among subjects with normal lung function, plus other cut-points among the COPD population, were evaluated post hoc. FINDINGS: Most participants had Eos >2%; 70.7% with spirometry-defined COPD and 65.5% with normal lung function. Older age, male gender, and severe current asthma were significantly associated with Eos >2% in COPD subjects. The Eos ≤ 2% COPD group had higher reported rates of previous heart attack and anemia. Among participants with normal lung function, Eos > 2% was associated with being male, being overweight/obese, older age, hay fever, and congestive heart failure. INTERPRETATION: In this large US-based cohort, Eos > 2% was prevalent in participants with COPD and normal lung function. Among participants with COPD, Eos > 2% was associated with specific characteristics including lower rates of some co-morbidities; however, the clinical implications and relationships between Eos levels, COPD mechanisms, and risk of outcomes require further evaluation.

Risk of pneumonia with inhaled corticosteroid versus long-acting bronchodilator regimens in chronic obstructive pulmonary disease: a new-user cohort study.

INTRODUCTION: Observational studies using case-control designs have showed an increased risk of pneumonia associated with inhaled corticosteroid (ICS)-containing medications in patients with chronic obstructive pulmonary disease (COPD). New-user observational cohort designs may minimize biases associated with previous case-control designs. OBJECTIVE: To estimate the association between ICS and pneumonia among new users of ICS relative to inhaled long-acting bronchodilator (LABD) monotherapy. METHODS: Pneumonia events in COPD patients ≥45 years old were compared among new users of ICS medications (n = 11,555; ICS, ICS/long-acting ß2-agonist [LABA] combination) and inhaled LABD monotherapies (n = 6,492; LABA, long-acting muscarinic antagonists) using Cox proportional hazards models, with propensity scores to adjust for confounding. SETTING: United Kingdom electronic medical records with linked hospitalization and mortality data (2002-2010). New users were censored at earliest of: pneumonia event, death, changing/discontinuing treatment, or end of follow-up. OUTCOMES: severe pneumonia (primary) and any pneumonia (secondary). RESULTS: Following adjustment, new use of ICS-containing medications was associated with an increased risk of pneumonia hospitalization (n = 322 events; HR = 1.55, 95% CI: 1.14, 2.10) and any pneumonia (n = 702 events; HR = 1.49, 95% CI: 1.22, 1.83). Crude incidence rates of any pneumonia were 48.7 and 30.9 per 1000 person years among the ICS-containing and LABD cohorts, respectively. Excess risk of pneumonia with ICS was reduced when requiring ≥1 month or ≥ 6 months of new use. There was an apparent dose-related effect, with greater risk at higher daily doses of ICS. There was evidence of channeling bias, with more severe patients prescribed ICS, for which the analysis may not have completely adjusted. CONCLUSIONS: The results of this new-user cohort study are consistent with published findings; ICS were associated with a 20-50% increased risk of pneumonia in COPD, which reduced with exposure time. This risk must be weighed against the benefits when prescribing ICS to patients with COPD.

Herpes simplex virus type-2 seropositivity among ever married women in South and north Vietnam: a population-based study.

OBJECTIVE: To investigate herpes simplex virus type-2 (HSV-2) seropositivity and associated risk factors in Vietnamese women. METHODS: Cross-sectional study with personal interviews and gynecological examinations among population-based samples of ever married women, aged 15 to 69 years, living in Ho Chi Minh City (HCMC) and Hanoi in 1997. Type-specific IgG antibodies against HSV-2 were detected using HerpeSelect ELISA (Focus Diagnostics). Adjusted prevalence ratios were estimated with log-binomial regression. RESULTS: HSV-2 seroprevalence was higher in 1106 women from HCMC (30.8%, 95% CI: 28.1-33.4, age-standardized to 2000 world standard population) than in 1170 women from Hanoi (8.8%, 95% CI: 7.1-10.5). In HCMC, HSV-2 seroprevalence was higher for women who were not married, HPV DNA positive, current hormonal contraceptive users, or had a history of multiple sexual partners or spontaneous abortion. HCMC seroprevalence was inversely associated with educational attainment, age at first intercourse, and age at first pregnancy. In the multivariable model for HCMC, a trend of increasing HSV-2 seroprevalence with age was observed, and prevalence ratios were nearly identical to age-adjusted prevalence ratios for marital status, age at first pregnancy, and HPV DNA positivity. CONCLUSIONS: HSV-2 was notably less prevalent in Hanoi than HCMC, where it was associated with traditional HSV-2 risk factors. These results are likely explained by socio-cultural, historical, economic, and demographic factors related to urban-rural and regional differences. Future population-based studies should include men and never-married women as a next step toward obtaining a more nearly complete picture of HSV-2 epidemiology in Vietnam.