Women with blood cancers are at substantially greater risk of severe adverse events with immunotherapy compared to men, a new study shows.

A review of adverse event data from 23,296 patients enrolled in 202 clinical trials for conditions including myeloma and lymphoma has shown that women had a 34% higher rate of adverse events than men for all systemic therapies and a 66% higher risk of severe symptomatic adverse events with immunotherapy.

The findings, published in the Journal of Clinical Oncology, showed that sex disparities in immunotherapy-related adverse events were greatest for haematological toxicity, gastrointestinal adverse events and symptomatic adverse effects such as sleep disruption.

Researchers at the Fred Hutchinson Cancer Research Center, Seattle, analysed adverse event data from 8,838 female and 14,458 male patients involved in clinical trials in which they received immunotherapy, targeted therapy and/or chemotherapy.

Overall, 65% of patients experienced one or more severe (grade 3 and above) adverse event, and women had a significantly higher risk than men of having a severe adverse events with any therapy ( 68.6% v 62.2%).

For immunotherapy, women had an almost 50% higher increased risk of a severe adverse event compared with men (odds ratio 1.49; P > .001). The discrepancy was greatest for severe symptomatic adverse events (33.7% vs 25.4%, OR 0.66), and was also significant for haematologic adverse events (22.1% vs 18.4%, OR 0.32). No statistically significant sex differences in risk of non-haematologic adverse events were found with immunotherapy.

For targeted therapy there was a significant 34% higher rate of severe adverse events for women than men (30.1% vs 24.6%).

For severe (grade 3 and above) symptomatic adverse events the categories with the greatest sex differences included miscellaneous symptomatic (OR 5.07), respiratory (OR 1.73), gastrointestinal (OR 1.49) and sleep disruption (OR 1. 48).

The study also showed that women were more likely than men to have a wider range of severe adverse events than men when treated with immunotherapy (51.0% v 41.7% having more than five adverse events, OR 1.57).

The study authors said there were several possible explanations for sex differences in adverse events with immunotherapy, including body composition leading to women receiving  a greater relative dose compared to men, or pharmacodynamic and pharmacokinetic differences between the sexes. There could also be genetic and gut microbiome differences that modulated immune responses, they suggested.

“If confirmed, our findings suggest that underlying mechanisms may result in generalised worse toxicity outcomes for women, with or without corresponding survival improvements or detriments,” they wrote.

Therefore better understanding was needed of sex differences in immunotherapy side effects to allow individualisation of treatment and maximise the benefits over toxicity as part of  ‘precision therapy’, they suggested.