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4456 Fertility and Gonadal Function after First-Line Treatment with Nivolumab-AVD in Hodgkin Lymphoma Patients: An Analysis from the Phase II GHSG Nivahl Trial

Program: Oral and Poster Abstracts
Session: 624. Hodgkin Lymphomas and T/NK cell Lymphomas: Clinical and Epidemiological: Poster III
Hematology Disease Topics & Pathways:
Research, clinical trials, Hodgkin lymphoma, Biological therapies, Lymphomas, Non-Biological therapies, Clinical Research, Chemotherapy, Combination therapy, Checkpoint Inhibitor, patient-reported outcomes, Diseases, Therapies, Immunotherapy, Lymphoid Malignancies, survivorship
Monday, December 11, 2023, 6:00 PM-8:00 PM

Paul J Bröckelmann, MD1*, Ina Bühnen2*, Peter Herhaus, MD3*, Julia Meissner, MD4*, Karolin Trautmann-Grill, MD5*, Horst Müller, PhD1*, Michael Fuchs, MD1*, Bastian von Tresckow, MD6, Peter Borchmann7, Andreas Engert, MD1* and Karolin Behringer, MD1*

1Department I of Internal Medicine, German Hodgkin Study Group (GHSG), University Hospital of Cologne, Cologne, Germany
2Department I of Internal Medicine, German Hodgkin Study Group (GHSG), University Hospital Cologne, Cologne, Germany
3Clinic and Policlinic for Internal Medicine III, Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Munich, Germany
4Medicine V, University Hospital of Heidelberg, Heidelberg, Germany
5Medical Clinic I, University Hospital Carl Gustav Carus, Dresden, Germany
6Department of Hematology and Stem Cell Transplantation, West German Cancer Center Essen, Essen, Germany
7Department I of Internal Medicine, German Hodgkin Study Group (GHSG), University Hospital of Cologne, Koeln, Germany

Background: First-line treatment of patients with classical Hodgkin lymphoma (HL) with anti-PD1 antibodies in combination with AVD chemotherapy is highly effective across risk-groups. Based on encouraging phase II and ongoing phase III trials, anti-PD1 based first-line treatment may hence soon become a first-line treatment option. To date, no data on fertility and gonadal function after anti-PD1 based first-line HL treatment is available. Herein, we present data on pregnancies and gonadal function in patients treated within the randomized GHSG phase II NIVAHL trial.

Methods: NIVAHL enrolled 109 patients aged 18-60 years with first diagnosis of early-stage unfavorable HL to receive either fully concomitant (4xN-AVD; group A) or sequential (4xN, 2xN-AVD, 2xAVD; group B) nivolumab-based 1st-line treatment, each followed by 30Gy involved-site radiotherapy (IS-RT). The primary and final analyses showed excellent efficacy and an acceptable safety profile after 1- and 3-years of follow up; details were previously published (Bröckelmann et al. JAMA Oncol 2020 & JCO 2023). Data on pregnancies and births as well as sexual hormones prior, during and after treatment were collected via standardized case report forms. The cohort for this descriptive analysis included women <40 and men <50 years of age.

Results: A total of 87 patients (55% female, 51% treatment group A) with a median age of 25 (range 18-49) were eligible for this analysis. Patient characteristics were well balanced between treatment groups and patients presented predominantly with stage IIA disease (75.3%) and presence of the risk factors ≥3 nodal areas (75%), elevated ESR (44%) and bulky mediastinal disease (20.2%). Cryopreservation prior start of treatment was performed in 39.6% of female and 74.4% of male patients. With a median follow-up (FU) of 41 months, a total of 11 pregnancies were documented (12.6%; 9 in female patients, 2 in partners of male patients). These resulted in 8 documented live births (2 abortions, 1 missing info), with none using assisted reproductive techniques. In female patients, median hormone levels remained relatively stable from baseline to 12-24 months of FU for FSH (4.7 -> 4.3 U/l), LH (6 -> 7.2 U/l) and AMH (2.3 -> 2.8 ug/l) while an increase of estradiol was observed (53.6 -> 102 ng/l). Similar trajectories of largely stable hormone levels were observed when stratifying female patients by age groups (i.e. 18-29 and 30-39 years). Women ≥30 years presented higher median FSH (6.1 vs 4.7 U/l) and lower estradiol values (48.8 vs 53.6 ng/l) compared to younger women at baseline, however, presented with similar median FSH levels at 12-24 months of FU (4.2 and 4.4 U/l, respectively). In male patients, hormone levels also remained stable from baseline to 12-24 months of FU for FSH (4.2 -> 4.2 U/l), LH (4.1 -> 3.9 U/l), testosterone (4 -> 5.6 ug/l) and inhibin B (159.4 -> 180 ng/l). More detailed analyses regarding hormonal trajectories of individual patients and stratifications by treatment group are ongoing and will be presented at the meeting.

Conclusion: This analysis of pregnancies, births and sex hormones after first-line HL treatment with N-AVD indicates preserved gonadal function in the majority of both female and male patients.

Disclosures: Bröckelmann: MSD: Honoraria, Research Funding; Celgene: Other: Travel Grant; BeiGene: Consultancy, Honoraria, Research Funding; BMS: Honoraria, Research Funding; Stemline: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding. Trautmann-Grill: Roche: Honoraria; Takeda: Honoraria. von Tresckow: Allogene: Consultancy; BMS/Celgene: Consultancy, Honoraria; Cerus: Consultancy; Incyte: Consultancy, Honoraria; IQVIA: Consultancy; Gilead Kite: Consultancy, Other: Travel Support; Miltenyi: Consultancy; Novartis: Consultancy, Honoraria, Other: Travel Support, Research Funding; Noscendo: Consultancy; Pentixapharm: Consultancy; Roche: Consultancy, Honoraria, Other: Travel Support; Amgen: Consultancy; Pfizer: Consultancy; Takeda: Consultancy, Honoraria, Other: Travel Support, Research Funding; MSD: Consultancy, Honoraria, Other: Travel Support, Research Funding; AbbVie: Other: Travel Support; AstraZeneca: Honoraria, Other: Travel Support; Lilly: Consultancy, Honoraria, Other: Travel Support; Pierre Fabre: Other: Travel support. Borchmann: Amgen: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Merck Sharp & Dohme: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy; Takeda Oncology: Consultancy, Research Funding; MPI: Research Funding.

OffLabel Disclosure: Nivolumab is not currently approved for first-line treatment of Hodgkin lymphoma.

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