Vagal nerve activity was found to be an independent predictor of prognosis in diffuse large B-cell lymphoma (DLBCL) and multiple myeloma (MM). These findings were published in the Journal of Clinical Medicine.

Despite advances in the treatment of DLBCL and MM, overall survival rates are 60% to 70% and 67%, respectively. Therefore, researchers are searching for a prognostic predictor that would also inhibits multiple biological factors that lead to cancer progression. The vagal nerve could be that prognostic protective factor; the vagus is a major branch of the parasympathetic nervous system.

Heart rate variability (HRV) — ie, fluctuations in the interval between normal heart beats — is an indicator of vagal activity, and can be noninvasively measured by ECG. High HRV is hypothesized to be related to slower tumor progression because it inhibits the underlying mechanisms that contribute to cancer onset and progression.

Continue Reading

Epidemiologic evidence shows that higher HRV is an independent predator of lower tumor marker levels and even prolonged survival in some solid cancers. The researchers sought to determine if this could be relevant to hematologic cancers.

This study included 29 patients with relapsed/refractory (R/R) DLBCL and 37 patients with MM. The patients with R/R DBCL underwent chimeric antigen receptor T-cell (CAR-T) therapy. The patients with multiple myeloma underwent autologous hematopoietic cell transplantation (autoHCT).

In patients with R/R DLBCL, HRV, measured as the standard deviation between r-r intervals (SDNN), was a predictor of overall survival independent of confounders. “Patients with higher HRV had 4.85 times greater chances of surviving compared to those with low HRV independent of multiple confounders, including disease severity,” the researchers noted.

In patients with MM, HRV, measured as the root mean square of successive differences between r-r intervals (RMSSD), was a predictor of progression-free survival independent of confounders. “Patients with higher HRV had 5.23 times greater chances of not progressing compared to those with low HRV,” the researchers noted in their report.

This study was limited by its small sample sizes, which may reduce the generalizability of the findings, and the follow-up periods were relatively short. Additionally, HRV was measured retroactively in a 10-second ECG, which did not enable the researchers to determine HRV parameters such as high frequency HRV.

Despite these limitations, the researchers’ consistent results demonstrate that vagal nerve activity, indexed by HRV, is a robust independent prognostic predictor in blood cancers. “Future studies should examine the causal and therapeutic roles of the vagus nerve in blood cancers by performing a randomized, controlled trial. Such a trial can include vagal activation by electric stimulation, biofeedback, medications, etc,” they suggested.


Atar O, Ram R, Avivi I, et al. Vagal nerve activity predicts prognosis in diffused large B-cell lymphoma and multiple myeloma. J Clin Med. 2023;12(3):908.

This article originally appeared on Oncology Nurse Advisor