In a prospective analysis from the phase III Lymphoma Study Association AHL2011 trial reported in the Journal of Clinical Oncology, Demeestere et al found that patients with advanced Hodgkin lymphoma receiving a positron-emission tomography (PET)-adapted regimen had a reduced risk of gonadal dysfunction vs standard chemotherapy. The aim of this substudy was to investigate the benefit of this strategy in gonadal function and fertility in patients younger than age 45.
The trial, conducted at sites in France and Belgium, showed that treatment with a low-intensity regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) after two cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP-escalated) in patients with early PET response reduced toxicity and did not impair disease control vs standard treatment (six cycles of BEACOPP-escalated).
Study Details
The current analysis included 145 women (75 in PET-driven group, 70 in standard group) and 424 men (210 in PET-driven group, 214 in standard group) younger than age 45 enrolled between May 2011 and April 2014. A total of 34 patients (11.9%) in the PET-driven group had had positive early PET findings and continued with BEACOPP-escalated cycles. Ovarian and testicular function were assessed at baseline, at the end of treatment, and over up to 5 years of follow-up.
Key Findings
Risk of premature ovarian insufficiency indicated by follicle-stimulating hormone level > 24 IU/L (odds ratio [OR] = 0.20, 95% confidence interval [CI] = 0.08–0.50, P = .001) and risk of low ovarian reserve indicated by antimullerian hormone level < 0.5 ng/mL (OR = 0.15, 95% CI = 0.04–0.56, P = .005) were significantly reduced in the PET-driven vs standard therapy group.
Ovarian function recovery was significantly more common in the PET-driven group (hazard ratio = 2.52, 95% CI = 1.73–3.67, P < .0001); after 2 years of follow-up, recovery had occurred in 73.7% vs 42.6% of patients. No significant difference in pregnancy rates was observed (38.6% vs 41.4%, P = .65)
Sperm recovery was more common in the PET-driven group, with significant differences (all P < .05) vs the standard group being observed in sperm concentration at 1, 2 to 3, and 4 to 5 years of follow-up. At a median of 29 months of follow-up, azoospermia was observed in 7 (33.3%) of 21 vs 26 (96.3%) of 27 patients (P = .008). However, sperm concentration values did not return to baseline levels during follow-up. No difference in testosterone levels was observed between groups.
Patients in the PET-driven group had lower risk of severe testicular damage (OR = 0.26, 95% CI = 0.13–0.50, P < .0001) and a higher likelihood of achieving pregnancy (9.5% vs 2.8%; OR = 3.7, 95% CI = 1.4–9.3, P = .004).
The investigators concluded, “Although both treatments affected ovarian reserve and spermatogenesis, the PET-driven strategy decreased the risk of gonadal dysfunction and infertility in [patients with] advanced Hodgkin lymphoma.”
Isabelle Demeestere, MD, PhD, of the Research Laboratory on Human Reproduction, Campus Erasme, Université Libre de Bruxelles, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was funded by Fonds Erasme, Fonds National de la Recherche Scientifique, and Program Hospitalier de Recherche Clinique 2010. For full disclosures of the study authors, visit ascopubs.org.
