Outcome of older myeloma patients in relationship to comorbidities and availability of second-generation novel agents in a real-life setting.

Major improvements in outcome of older patients with multiple myeloma (MM) have been achieved with the introduction of novel agents. Their impact in real-life treatment of older patients is unclear. In this single center retrospective study, we analyzed the outcome of patients >65 years treated with first-generation (FGNA) and second-generation novel agents (SGNA) within two time periods 2012-2014 and 2015-2017. Patients were analyzed based on age, Charlson Comorbidity Index (CCI), International Staging System stage, year of diagnosis and withdrawal of agents due to toxicities. Overall 96 patients were included for analysis. Median age was 73 years (range 65-90), 55 (57%) patients were 65-75 years and 41 (43%) were >75 years old. 84 patients received a first-line therapy, whereas 45 patients had ≥2 lines of systemic therapy. 20 patients were consolidated with autologous stem cell transplantation. 12 patients had no systemic therapy at all. In 17 of 21 cases a FGNA and in 4 of 21 a SGNA was withdrawn due to toxicity. Median overall survival (OS) for all patients with systemic therapy was 4.75 years (95% CI, 3.05-NA). Borderline significant improvement of OS was observed in patients diagnosed 2015-2017 compared to 2012-2014 with HR 0.57 (95% CI, 0.31-1.02) p = 0.06. OS significantly differed for comorbid patients with low and intermediate risk CCI, HR 1.94 (95% CI, 1.07-3.54), p = 0.03 in the overall population. OS in patients treated with SGNA was not significantly different in patients with intermediate versus low risk CCI (HR 1.48 (95% CI 0.43-5.14, p = 0.54)). In conclusion, we found a trend toward improved survival for older MM patients after the introduction of novel agents during the observed time period. In patients treated with SGNA a smaller effect that comorbidity negatively affects survival was observed.

Outdoor Temperature Influences Cold Induced Thermogenesis in Humans.

Objective: Energy expenditure (EE) increases in response to cold exposure, which is called cold induced thermogenesis (CIT). Brown adipose tissue (BAT) has been shown to contribute significantly to CIT in human adults. BAT activity and CIT are acutely influenced by ambient temperature. In the present study, we investigated the long-term effect of seasonal temperature variation on human CIT. Materials and Methods: We measured CIT in 56 healthy volunteers by indirect calorimetry. CIT was determined as difference between EE during warm conditions (EEwarm) and after a defined cold stimulus (EEcold). We recorded skin temperatures at eleven anatomically predefined locations, including the supraclavicular region, which is adjacent to the main human BAT depot. We analyzed the relation of EE, CIT and skin temperatures to the daily minimum, maximum and mean outdoor temperature averaged over 7 or 30 days, respectively, prior to the corresponding study visit by linear regression. Results: We observed a significant inverse correlation between outdoor temperatures and EEcold and CIT, respectively, while EEwarm was not influenced. The daily maximum temperature averaged over 7 days correlated best with EEcold (R2 = 0.123, p = 0.008) and CIT (R2 = 0.200, p = 0.0005). The mean skin temperatures before and after cold exposure were not related to outdoor temperatures. However, the difference between supraclavicular and parasternal skin temperature after cold exposure was inversely related to the average maximum temperature during the preceding 7 days (R2 = 0.07575, p = 0.0221). Conclusion: CIT is significantly related to outdoor temperatures indicating dynamic adaption of thermogenesis and BAT activity to environmental stimuli in adult humans. Clinical Trial Registration: www.ClinicalTrials.gov, Identifier NCT02682706.