ISHL10 Abstract T027

The impact of treatment type and age on ovarian toxicity in the RATHL study

This analysis examined the differential effects upon ovarian function of the treatment strategies within the international RATHL study (NCT00678327). Women with newly diagnosed advanced HL (stages IIb to IV, IIa with bulk or ≥3 involved sites) had two cycles of ABVD followed by PET/CT scan. Those with negative scans were randomised to ABVD or AVD for 4 more cycles, those with positive scans were escalated to either BEACOPP-14 or escalated BEACOPP for 8-9 weeks. Reproductive hormones were measured in women in the main cohort of the trial (n=390) with additional samples taken in a sub-group for measurement of anti-Müllerian hormone (AMH) as a marker of the ovarian reserve (n=63). There were no differences between the ABVD and AVD groups. AMH fell markedly from baseline to end of treatment, but equally in all 3 groups. Thereafter, there was a return to concentrations not different from pre-treatment in the ABVD/AVD groups within 1 year, but no recovery in the BEACOPP groups over 3 years. An FSH threshold of >25IU/L was used to indicate premature ovarian insufficiency (POI). The prevalence of this threshold was substantially higher for women treated with BEACOPP than those treated with ABVD/AVD (see table), with longer and less complete recoveries. Patients aged over 35 were more likely to exhibit POI, especially after BEACOPP therapy. Pre-treatment AMH was associated with post-chemotherapy ovarian damage in all groups. ABVD/AVD regimens are regarded as low risk to fertility, and these results confirm the absence of detectable ovarian damage in women aged <35, although there was some evidence of ovarian toxicity in older women. Pre-treatment AMH may be of value to predict early POI and loss of fertility following treatment by identifying those women at particular risk who may wish to consider fertility preservation strategies.