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20-09-2018 | Lymphoma | News | Article

Hormonal biomarker shows ovarian toxicity of Hodgkin lymphoma treatment

medwireNews: Phase III trial data have highlighted the value of antimüllerian hormone as a biomarker of ovarian toxicity associated with different chemotherapy regimens for advanced Hodgkin lymphoma.

The study, by Richard Anderson (University of Edinburgh, UK) and colleagues, found that antimüllerian hormone concentration, an indirect marker of ovarian reserve, decreased substantially during treatment with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), AVD, or bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisolone (BEACOPP-14 or escalated BEACOPP).

At 1 year post-treatment, median levels of the hormone returned to baseline concentrations among the 57 women who received ABVD or AVD, but little recovery occurred among the 10 women who received BEACOPP.

Furthermore, recovery of ovarian function after treatment with ABVD or AVD was age-dependent, with full recovery of antimüllerian hormone seen in women younger than 35 years, but not in those aged 35 years or older.

This finding “indicates that age-specific discussions and consideration of fertility preservation procedures should be considered before treatment” for Hodgkin lymphoma, the researchers remark.

They add: “These considerations are of growing importance given the increasing age at which women are having children in developed countries.”

The prospective secondary substudy of the RATHL trial included women aged 18–45 years who had classic Hodgkin lymphoma of stage IIB–IV or IIA with adverse features. Baseline median antimüllerian hormone concentrations were 9.8 pmol/L among the women treated with ABVD or AVD and 6.8 pmol/L in those treated with BEACOPP.

Immediately after chemotherapy, median hormone concentrations fell to 1.7 and 0.08 pmol/L in the ABVD or AVD and BEACOPP groups, respectively. At 1 year, the median level recovered to 10.5 pmol/L in the ABVD or AVD group but was only 0.11 pmol/L in the BEACOPP group, with no further changes observed at 2 or 3 years post-treatment.

When the participants were stratified by age, Anderson and co-investigators found that antimüllerian hormone levels recovered to 127% of their baseline level among women in the ABVD/AVD group who were younger than 35 years of age, compared with just 37% recovery in those aged 35 years and older.

Of note, the pregnancy rate in the overall RATHL cohort of 391 participants did not differ substantially between the ABVD or AVD and BEACOPP groups (17 vs 13%).

This suggests that although “low concentrations of antimüllerian hormone do not preclude pregnancy in the short term, they probably do indicate a reduced interval to menopause and thus a shortened duration of opportunity to achieve pregnancy in the longer term,” Anderson et al remark in The Lancet Oncology.

Therefore “a low concentration of antimüllerian hormone after recovery from chemotherapy could identify women who should not unduly postpone pregnancy, and inform individualised discussion,” the authors add.

They caution, however, that “longer follow-up studies are needed to assess this interpretation.”

By Laura Cowen

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