Financial toxicity-associated nivolumab dose modifications in lymphoma patients: Real-world cohort from Armenia
Nivolumab is a standard-of-care treatment for relapsed/refractory (r/r) Hodgkin lymphoma (HL) and is approved for selected non-Hodgkin lymphoma (NHL) subtypes. However, high costs significantly restrict nivolumab accessibility, particularly in the developing world. This study aims to report treatment outcomes in patients with r/r HL and r/r NHL treated with standard or reduced doses of nivolumab in Armenia. A total of 16 patients diagnosed with HL and NHL between 2013 and 2023 (follow-up until March 2025) who received at least one nivolumab dose were included in the study. Primary endpoints: overall response rate (ORR), complete response (CR), partial response (PR), and disease progression (PD). Secondary endpoint: overall survival (OS) and safety description. Of the 16 patients, 9 (56.3%) were female. Median age at diagnosis: 37 years. Median follow-up duration: 37 months. Fifteen patients (93.8%) presented with advanced-stage disease. Seven patients (43.8%) were primary resistant. Thirteen (81.3%) experienced financial toxicity, receiving nivolumab at reduced doses. ORR: 9 patients (56.25%), CR: 4 patients (25%), PR: 5 (31.3%), PD: 7 (43.8%). Estimated OS at 12, 24, and 36 months was 91.7%, 81.5%, and 40.7%, respectively. Nivolumab ≥100 mg showed superior efficacy, with responses still seen at reduced doses and no severe adverse events. In conclusion, standard-dose nivolumab showed superior effectiveness in this cohort, though ORR was also observed with reduced doses. Approximately half of patients with r/r HL and NHL responded despite dose reduction. OS and safety were comparable to global data. Larger studies are needed to evaluate potential dose reduction in resource-limited settings.
- Cencini E, Bocchia M, Fabbri A. Nivolumab in relapsed/ refractory Hodgkin lymphoma: towards a new treatment strategy? Am J Blood Res. 2021;11(3):261-265.
- Ansell SM, Bröckelmann PJ, von Keudell G, et al. Nivolumab for relapsed/refractory classical Hodgkin lymphoma: 5-year survival from the pivotal phase 2 CheckMate 2025 study. Blood Adv. 2023;7(20):6266-6274. doi: 10.1182/bloodadvances.2023010334
- Younes A, Brody J, Carpio C, et al. Safety and efficacy of the combination of ibrutinib and nivolumab in patients with relapsed non-Hodgkin lymphoma or chronic lymphocytic leukemia. Blood. 2017;130:833-841. doi: 10.1182/blood.V130.Suppl_1.833.833
- Guo L, Zhang H, Chen B. Nivolumab as programmed death-1 (PD-1) inhibitor for targeted immunotherapy in tumor. J Cancer. 2017;8(3):410-416. doi: 10.7150/jca.17144
- Riaz N, Havel JJ, Makarov V, et al. Tumor and microenvironment evolution during immunotherapy with nivolumab. Cell. 2017;171(4):934-949. doi: 10.1016/j.cell.2017.09.028
- Harutyunyan L, Ter-Grigoryan A, Grigoryan H, et al. Treatment of relapsed and refractory lymphomas with nivolumab in a limited recourse country. J Immunother Cancer. 2022;10(Suppl 2):A445. doi: 10.1136/jitc-2022-SITC2022.0423
- Lepik KV, Fedorova LV, Kondakova EV, 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):e403. doi: 10.1097/HS9.0000000000000480
- Colunga-Pedraza PR, Vaquera-Alfaro HA, Guzmán- Martínez Z, et al. Optimizing resources: low-dose nivolumab combinations in the management of relapsed/refractory Hodgkin lymphoma. Ann Hematol. 2024;103(12):5607- 5614. doi: 10.1007/s00277-024-06098-9
- Jiménez-Labaig P, Mohamed F, Tan NJ, et al. Expanding access to cancer immunotherapy: a systematic review of low-dose PD-(L)1 inhibitor strategies. Eur J Cancer. 2025;225:115564. doi: 10.1016/j.ejca.2025.115564
- Patil VM, Noronha V, Menon N, et al. Low-dose immunotherapy in head and neck cancer: a randomized study. J Clin Oncol. 2023;41(2):222-232. doi: 10.1200/JCO.22.01015
- Unger JM, Shulman LN, Facktor MA, Nelson H, Fleury ME. National estimates of the participation of patients with cancer in clinical research studies based on Commission on Cancer accreditation data. J Clin Oncol. 2024;42(18):2139- 2148. doi: 10.1200/JCO.23.01030
- Yoo SH, Keam B, Kim M, et al. Low-dose nivolumab can be effective in non-small cell lung cancer: alternative option for financial toxicity. ESMO Open. 2018;3(5):e000332. doi: 10.1136/esmoopen-2018-000332
- Dee EC. Family and caregiver financial toxicity associated with cancer—A global, inequitable, and urgent consideration. JAMA Netw Open. 2023;6(6):e2319317. doi: 10.1001/jamanetworkopen.2023.19317
- Movsisyan A, Hambardzumyan L, Ghahramanyan N, et al. The experience of hematologic oncology in Armenia. OncoDaily Med J. 2024. doi: 10.69690/odmj-001-1124-250
- Trivedi C, John J, Karumathil S, et al. Efficacy of standard-dose versus low-dose nivolumab in relapsed/refractory Hodgkin lymphoma—A retrospective analysis. JCO Glob Oncol. 2026;12(2):e2500424. doi: 10.1200/GO-25-00424
- Gandhi KA, Shirsat A, Sharat Kumar HJ, et al. Pharmacokinetics and clinical outcomes of low-dose nivolumab relative to conventional dose in patients with advanced cancer. Cancer Chemother Pharmacol. 2024;94(5):659-668. doi: 10.1007/s00280-024-04697-x
