Nivolumab and pregnancy in patients with classical Hodgkin lymphoma

Introduction. Classical Hodgkin lymphoma (cHL) is predominantly diagnosed in women of reproductive age. The expanding use of PD-1 inhibitors in the treatment of cHL increases the likelihood of pregnancy being detected during immunotherapy. However, only a limited number of such observations have been described in the literature, which complicates the choice of an optimal management strategy for these patients.

Aim: to present two clinical case reports of patients with cHL: in the first, the beginning of pregnancy (4 weeks) occurred during nivolumab exposure; in the other patient, nivolumab was administered during the periconceptional period, 6 weeks before conception.

Main Findings. In the first case, pregnancy was diagnosed at 6 weeks of gestation during maintenance therapy with nivolumab 40 mg every 2 weeks (cumulative dose 600 mg); the last dose was administered at 4 weeks of gestation, and treatment was discontinued after pregnancy was confirmed. Spontaneous delivery occurred at 38 weeks: a boy, birth weight 2910 g, length 49 cm, Apgar scores 8 and 9. In the second case, pregnancy was diagnosed at 3 weeks of gestation after completion of the Nivo-DHAP course with nivolumab at a dose of 240 mg. After pregnancy was confirmed, antitumor treatment was discontinued. Delivery at 38 weeks: cesarean section, a girl, birth weight 3000 g, length 52 cm, Apgar scores 8 and 9. The presented clinical case reports add to the limited clinical data on the course of pregnancy during the use of PD-1 inhibitors and highlight the need for multidisciplinary management and individualized decision-making, taking into account the potential risks to the mother and the fetus.

1. Kaprin A.D., Starinskiy V.V., Petrova GV, eds. Malignant neoplasms in Russia in 2017 (morbidity and mortality). Moscow: MNIOI im PA Gertsena — filial FGBU “NMITs radiologii” Minzdrava Rossii; 2018 (In Russian).

2. Kravtsova A., Mangasarova Y., Zvonkov E., et al. Personalized nivolumab-based de-escalated strategy as frontline therapy for high-risk patients with classical Hodgkin lymphoma. HemaSphere. 2025;9(S1):1576–7. DOI: 10.1002/hem3.70153.

3. Fastova E.A., Mangasarova J.K., Gostiunina E.A., et al. Nivolumab as maintenance therapy for relapsed and refractory classical Hodgkin lymphoma. Gematologiya I Transfusiologiya. 2025;70(4):429–40 (In Russian). DOI: 10.35754/0234-5730-2025-70-4-429-440.

4. Pinnix C.C., Osborne E.M., Chihara D., et al. Maternal and Fetal Outcomes After Therapy for Hodgkin or Non-Hodgkin Lymphoma Diagnosed During Pregnancy. JAMA Oncol. 2016;2(8):1065–9. DOI: 10.1001/jamaoncol.2016.1396.

5. Wolters V., Heimovaara J., Maggen C., et al. Management of pregnancy in women with cancer. Int J Gynecol Cancer. 2021;31(3):314–22. DOI: 10.1136/ijgc-2020-001776.

6. U.S. Food and Drug Administration. OPDIVO (nivolumab) injection, for intravenous use. Prescribing information. 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/125554s132lbl.pdf

7. U.S. Food and Drug Administration. KEYTRUDA (pembrolizumab) injection, for intravenous use. Prescribing information. 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/125514s096lbl.pdf

8. Saji F., Samejima Y., Kamiura S., Koyama M. Dynamics of immunoglobulins at the feto-maternal interface. Rev Reprod. 1999;4(2):81–9. DOI: 10.1530/ror.0.0040081.

9. Guleria I, Khosroshahi A., Ansari M.J., et al. A critical role for the programmed death ligand 1 in fetomaternal tolerance. J Exp Med. 2005;202(2):231–7. DOI: 10.1084/jem.20050019.

10. Meggyes M., Miko E., Szigeti B., et al. The importance of the PD-1/PD-L1 pathway at the maternal-fetal interface. BMC Pregnancy Childbirth. 2019;19(1):74. DOI: 10.1186/s12884-019-2218-6.

11. Guo C., Cai P., Jin L., et al. Single-cell profiling of the human decidual immune microenvironment in patients with recurrent pregnancy loss. Cell Discov. 2021;7(1):1. DOI: 10.1038/s41421-020-00236-z.

12. Guo R., Jiang S., Zhang J., et al. PD-1 mediates decidual γδ T cells cytotoxicity during recurrent pregnancy loss. Am J Reprod Immunol. 2022;88(3):e13562. DOI: 10.1111/aji.13562.

13. Evens A.M., Brandt J.S., Peer C.J., et al. Checkpoint inhibitor immunotherapy during pregnancy for relapsed-refractory Hodgkin lymphoma. Am J Hematol. 2022;97(6):833–8. DOI: 10.1002/ajh.26527

14. Mastricci A.L., Sorrentino F., Giansiracusa E., et al. Successful Pregnancy Outcome in a Patient Treated with Pembrolizumab and Exposed to Fluoro-Deoxyglucose (18F-FDG) PET/CT: Case Report and Review of Literature. Biomedicines. 2025;13(1):140. DOI: 10.3390/biomedicines13010140.

15. Hutson J.R., Eastabrook G., Garcia-Bournissen F. Pregnancy outcome after early exposure to nivolumab, a PD-1 checkpoint inhibitor for relapsed Hodgkin’s lymphoma. Clin Toxicol. 2022;60(4):535–6. DOI: 10.1080/15563650.2021.1981361.

16. Anami Y., Minami S., Kumegawa A., et al. Malignant melanoma treated with pembrolizumab during pregnancy: A case report and review of the literature. Mol Clin Oncol. 2021;15(5):242. DOI: 10.3892/mco.2021.2404.

17. Schneider C., Pozsgai M., Nemeth C., et al. A Healthy Pregnancy During Treatment of Metastatic Melanoma with Immune Checkpoint Inhibitors: A Case Report. J Clin Med. 2025;14(23):8591. DOI: 10.3390/jcm14238591.

18. Haiduk J., Ziemer M., Pregnancy in a patient with metastatic uveal melanoma treated with nivolumab. J Dtsch Dermatol Ges. 2021;19(5):762–5. DOI: 10.1111/ddg.14463.

19. Gougis P., Hamy A.S., Jochum F., et al. Immune Checkpoint Inhibitor Use During Pregnancy and Outcomes in Pregnant Individuals and Newborns. JAMA Netw Open. 2024;7(4):e245625. DOI: 10.1001/jamanetworkopen.2024.5625.

20. Baarslag M.A., Heimovaara J.H., Borgers J.S.W., et al. Severe Immune-Related Enteritis after In Utero Exposure to Pembrolizumab. N Engl J Med. 2023;389(19):1790–6. DOI: 10.1056/NEJMoa2308135.

21. Hasenclever D., Diehl V. A prognostic score for advanced Hodgkin’s disease. International Prognostic Factors Project on Advanced Hodgkin’s Disease. N Engl J Med. 1998;339(21):1506–14. DOI: 10.1056/NEJM199811193392104.

22. Meignan M., Gallamini A., Meignan M., et al. Report on the First International Workshop on Interim-PET-Scan in Lymphoma. Leuk Lymphoma. 2009;50(8):1257–60. DOI: 10.1080/10428190903040048.

23. Xu W., Moor R.J., Walpole E.T., Atkinson V.G. Pregnancy with successful foetal and maternal outcome in a melanoma patient treated with nivolumab in the first trimester: case report and review of the literature. Melanoma Res. 2019;29(3):333–7. DOI: 10.1097/CMR.0000000000000586.

24. Piemonti L., Vettor L., Contro E. A Case Report of Metastatic Gastric Cancer Treated with Pembrolizumab during Pregnancy. Fetal Diagn Ther. 2024;51(5):493–9. DOI: 10.1159/000540000.

25. Gambichler T., Susok L. Uncomplicated pregnancy and delivery under ongoing nivolumab therapy for metastatic melanoma. Melanoma Res. 2022;32(2):131–2. DOI: 10.1097/CMR.0000000000000801.

26. Rajczykowski M., Olbryt M., Galwas K., et al. Sustained Immunotherapy Response in Metastatic Brain Melanoma Through 2 Pregnancies. Am J Case Rep. 2025;26:e945533. DOI: 10.12659/AJCR.945533.

27. Lepik K.V., Fedorova L.V., Kondakova E.V., et al. A Phase 2 Study of Nivolumab Using a Fixed Dose of 40 mg (Nivo40) in Patients With Relapsed/Refractory Hodgkin Lymphoma. Hemasphere. 2020;4(5):e480. DOI: 10.1097/HS9.0000000000000480.