Study Finds Link Between Vitamin D Levels at Start of Immunotherapy and Overall Survival

A patient’s vitamin D levels at start of immunotherapy to treat cancer can be an indicator of overall survival, according to findings presented last month during the 2024 American Society of Clinical Oncology Annual Meeting.¹

Vitamin D | Image credit: Getty Images

Investigators from the University of Manchester in the United Kingdom were interested in whether seasonal factors, such as viruses, allergens, or ultraviolet exposure, could alter the effectiveness of immune checkpoint inhibitors, since these factors are known to affect the immune system itself.

Other research has shown that factors that affect immune response can impact outcomes after immunotherapy. For example, patients who receive immunotherapy before noon have been reported to have improved survival than those who have it later in the day.²

For this investigation, the University of Manchester team examined both the relationship between seasonal differences and response to immunotherapy, as well as patients’ baseline levels of vitamin D and response to immunotherapy.¹ However, a comparatively small number of patients in the study had recorded vitamin D levels.

Investigators evaluated patients who received immune checkpoint inhibitors at The Christie Hospital in the UK between 2017 and 2022. They compared patients treated in the winter vs summer months. They used 2 different windows for their comparisons: First, they compared outcomes for patients whose treatment began between November to April vs those whose treatment began May to October; then, they compared those with treatment starts in the more narrow windows of December through February vs June through August.

Where data were available, associations of baseline vitamin D levels and vitamin D supplements with OS were estimated, along with the association between the season of immune checkpoint inhibitor (ICI) initiation and OS in patients with normal vitamin D and/or those taking vitamin D supplements, the authors wrote.

A total of 3010 patients were included in the analysis, and 1804 OS events took place with median follow-up of 36.4 months. ICI indications included the following:

• Pembrolizumab (Keytruda) or atezolizumab (Tecentriq) for advanced non–small cell lung cancer (NSCLC): in first line (304 patients), median OS, 17 months; in second line (197 patients), median OS, 10.7 months;
• Pembrolizumab plus chemotherapy for advanced NSCLC (288 patients): median OS, 16.3 months;
• Pembrolizumab or nivolumab for advanced melanoma (211 patients): median OS, 25.2 months; adjuvant melanoma (226 patients), median OS, not reached;
• Ipilimumab plus nivolumab for melanoma (203 patients): median OS, 45.4 months;
• Ipilimumab plus nivolumab for renal cancer (129 patients): median OS, 38.6 months.

Confounders were balanced across seasons of ICI initiation, including gender, age, body mass index, and cancer setting. A slightly higher share of patients (52%) started treatment in the May to October window than in the November to April window (48%).

Results. Season of ICI initiation was not associated with OS. The November to April window of initiation had a median OS of 20.8 to 20.5 months (HR, 1.01; 95% CI, 0.92-1.11); while the December to February vs June to August comparison was 20.0 months vs 21.3 months (HR, 0.97; 95% CI, 0.85-1.10).

Among patients with vitamin D data, 214 patients had baseline levels and 96 received supplements before starting ICI treatment. Vitamin D deficiency was highest in February (23.6%) and lowest in August (1.1%). Among 209 patients with normal vitamin D levels or receiving supplements, the season of initiation was not associated with OS; November to April vs May to October median OS was 45.4 months vs 43.4 months (HR, 0.93; 95% CI, 0.63-1.53).

However, vitamin D deficiency (37 patients) was associated with shorter OS (HR, 2.06; 95% CI, 1.21-3.52) and supplementation was associated with longer OS (HR, 0.69; 95% CI, 0.52-0.92).

“While [vitamin D] deficiency and supplementation were associated with OS, season of ICI initiation was not,” the investigators concluded. “These results provide reassurance the OS benefits of ICIs remain similar irrespective of time of year of initiation despite seasonal factors that may influence the immune system.”

References

1. Kennedy O, Ali N, Lee R. Seasonal patterns in immunotherapy outcomes. J Clin Oncol. 2024;42(suppl 16); abstr e14684. doi:10.1200/JCO.2024.42.16_suppl.e14684

2. Caffrey M. Immunotherapy before noon linked to improved survival in mRCC. AJMC^®. March 28, 2024. Accessed July 3, 2024. https://www.ajmc.com/view/immunotherapy-before-noon-linked-to-improved-survival-in-mrcc