Anderson RA, et al. - In women with Hodgkin's lymphoma treated with different chemotherapy regimens, researchers sought risk factors for the extent of ovarian damage in order to provide correct advice on fertility preservation options. Women older than 35 years treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or AVD vs younger women exhibited reduced recovery of ovarian function; this suggests the possible attenuation their reproductive lifespan due to this treatment and supports discussing fertility preservation first. The potential high gonadotoxicity of BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisolone) should be discussed with women getting this treatment.

Methods

• Based on availability of participants at recruiting sites in the UK, female participants, aged 18–45 years, were recruited from the randomized phase 3 RATHL trial.
• In the RATHL trial, mainly the cases with histologically confirmed classic Hodgkin's lymphoma, stage IIB–IV or IIA with adverse features (bulky disease or more than two sites of involvement), no previous treatments, and a performance status of 0–3 were eligible to be included.
• As part of RATHL, two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or AVD were received by the participants, followed by an interim PET-CT scan.
• Randomization (1:1) was done with participants who had negative interim scans (PET score of 1 to 3 according to the Lugano classification), via minimization, stratified by interim PET score and study center, to continue ABVD or AVD for four more cycles.
• Escalation to treatment with bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisolone (BEACOPP-14 or escalated BEACOPP) for four cycles was chosen for participants with positive scans (PET score of 4 or 5).
• For the protocol-driven prospective cohort substudy, serum antimüllerian hormone and follicle-stimulating hormone measurements were used to evaluate ovarian function before treatment, during chemotherapy, and then annually for 3 years.

Results

• Recruitment of 67 eligible participants was done between December 13, 2010 and December 19, 2012, for this prospective cohort study; 57 were treated with ABVD or AVD (ABVD-AVD group) and ten BEACOPP-14 or escalated BEACOPP (BEACOPP group).
• Follow-up was fixed at 3 years.
• During both chemotherapy regimens, decrease in antimüllerian hormone concentrations was observed.
• Recovery of antimüllerian hormone concentrations to a median of 10.5 pmol/L (IQR 4.3–17.3) was observed in the ABVD-AVD group at 1 year after chemotherapy, but little recovery was seen following BEACOPP (median 0.11 pmol/L [0.07–0.20]).
• Findings also showed an impact of age on the extent of ovarian function recovery; participants aged 35 years or older in the ABVD-AVD group exhibited antimüllerian hormone recovery to 37% (SD 10) of their before treatment concentrations, vs full recovery to 127% (SD 12) in those younger than 35 years (p<0.0001).
• By 2 years, the occurrence of follicle-stimulating hormone recovery to less than 25 IU/L was noted for 95% of women younger than 35 years in the ABVD-AVD group and was found to be dependent on age (hazard ratio 0.49, 95% CI 0.37–0.65; p<0.0001).