Association between extreme heat exposures and survival in patients with multiple myeloma Free

Introduction Climate change has far-reaching health implications through a variety of exposure pathways, including heat stress from increased ambient temperatures. Heat stress can cause morbidity and mortality directly through heat stroke and indirectly through worsening of preexisting renal dysfunction, which itself increases susceptibility to heat. Patients with multiple myeloma (MM) are often older and develop renal dysfunction. The health impacts of extreme heat on patients with MM is not well understood. We investigated the association between extreme heat exposure and overall survival in patients with MM.

Methods Adults diagnosed with MM from January 1, 2004 to December 31, 2022 were identified from the National Cancer Database (NCDB), a hospital-based cancer registry that comprises 70% of all new cancer diagnoses in the United States. Daily maximum temperatures were extracted from Daymet, a 1 x 1 kilometer gridded temperature database for North America. These gridded data were spatially aggregated to the ZIP code level, and temperatures at the patients' zip code of residence at time of MM diagnosis were extracted. Exposure to extreme heat was defined as one or more consecutive days within the first week following date of diagnosis with a maximum daily temperature exceeding the 95^th percentile threshold of the historical temperature from 1992 to 2021 for the same month and ZIP code during the warm season (May to October). This peri-diagnostic period was selected as this is when MM is not yet controlled, and renal related injury is likely to occur. As health impacts can intensify as exposure to an extreme heat event lengthens, consecutive days of extreme heat exposure were also recorded. The primary outcome was overall survival defined as number of days between date of diagnosis and date of last contact or study end (December 31, 2022), whichever came first. Multivariable Cox proportional hazard analyses were performed adjusting for age, sex, comorbidity burden, and year of diagnosis. Sensitivity analyses were performed with alternative thresholds for extreme heat (97^th percentile) and exposure periods (one week before and after diagnosis). Additional analyses using comorbidity data in NCDB were performed to assess effect modification by kidney disease (acute, chronic, or either) on the association between exposure to extreme heat and overall survival (adjusted for age, sex, and year of diagnosis).

Results There were 350757 patients diagnosed with MM in the cohort. During the first week following MM diagnosis, the number of patients exposed to each duration of extreme heat was as follows: ≥1 day (36415; 10.38%), ≥2 consecutive days (17160; 4.89%), ≥3 consecutive days (7480; 2.13%), ≥4 consecutive days (3051; 0.87%), ≥5 consecutive days (1249; 0.36%), ≥6 consecutive days (548; 0.16%), and 7 consecutive days (235; 0.07%). Survival of patients exposed to 1, 2, or 3 days of extreme heat was relatively unaffected, with hazard ratios (HRs) of death between 0.98-0.99 compared to unexposed patients. For patients exposed to 4 or more days of extreme heat, the HR of death increased in a dose-dependent manner. The adjusted HR of death for those exposed to ≥4 consecutive days of extreme heat was 1.09 (95% Confidence Interval [CI]: 1.04-1.14, p=0.001). This risk increased further as the extreme heat exposure lengthened: ≥5 consecutive days (HR: 1.10, 95% CI: 1.03-1.19, p=0.009), ≥6 consecutive days (HR: 1.14, 95% CI: 1.02–1.28, p=0.03), and 7 consecutive days (HR: 1.18, 95% CI: 0.99–1.40, p=0.07). Similar trends were seen in sensitivity analyses with alternative thresholds for extreme heat (97^th percentile) and exposure period (one week before and after MM diagnosis). Using the coefficient of the interaction term, presence of kidney disease did not modify the association between heat exposure and mortality.

ConclusionsExposure to 4 or more consecutive days of extreme heat within one week following MM diagnosis is associated with an increased risk of death. Given rising temperatures due to climate change, future studies should evaluate modifiable factors contributing to this observed association to protect people diagnosed with multiple myeloma during extreme heat events.