Impact of Intensified Chemoimmunotherapy Regimens in Aggressive Non-Hodgkin Lymphoma on Reproduction Patterns

Concerns about treatment-related fertility impairment are common among young adult lymphoma survivors. Evidence on the impact of treatment for aggressive non-Hodgkin lymphoma (NHL) on future childbearing is limited, although many individuals of reproductive age are affected. This matched cohort study identified male (18-52 years) and female (18-40 years) patients with aggressive NHL between 2007 and 2018 in Sweden and the south-east health-care region in Norway, and matched lymphoma-free comparators. Adjusted hazard ratios (aHRs) comparing childbirth rates in patients treated with primary intensive chemoimmunotherapy (CIT) (e.g., R-CHOEP and R-DA-EPOCH) to standard-of-care (R-CHOP), and to comparators, were estimated using Cox regression. Among 1037 young survivors of aggressive NHL, childbirth rates did not differ significantly by treatment intensity (intensive vs. standard CIT) in females (aHR: 0.61, 95% CI: 0.32-1.13) or males (aHR: 1.20, 95% CI: 0.68-2.09), overall or when stratified by time since diagnosis (< 3 and 3-10 years). However, females treated with intensive CIT had lower childbirth rates than comparators during the first 3 years after diagnosis (aHR: 0.52, 95% CI: 0.30-0.88), but not thereafter (aHR: 1.06, 95% CI: 0.57-1.96). A similar pattern was not seen in males. In Sweden, eight children (three with support from assisted reproductive techniques) were born after stem cell transplantation. In conclusion, childbirth rates did not differ by CIT intensity among survivors of aggressive NHL. Although rates were temporarily reduced in females during the treatment and recovery period after diagnosis, subsequent rates were similar to comparators. These findings provide reassurance, while highlighting the importance of early and ongoing fertility counseling.