Efficacy of Standard-Dose Versus Low-Dose Nivolumab in Relapsed/Refractory Hodgkin Lymphoma-A Retrospective Analysis.

Abstract

As there is a paucity of data comparing outcomes with different dosing regimens of PD-1 inhibitors in relapsed/refractory Hodgkin lymphoma (R/R HL), this retrospective analysis was undertaken to compare the efficacy of low-dose nivolumab (fixed at 40 mg) with the standard dose of 3 mg/kg. Single-center retrospective analysis of patients with R/R HL who failed at least one salvage regimen and were treated with nivolumab between 2015 and 2023, at either 3 mg/kg (standard-dose nivolumab [SD-NIV]) or a flat dose of 40 mg (NIV40), both administered once in 2 weeks. Treatment response was assessed with ¹⁸F-labeled fluorodeoxyglucose-positron emission tomography-computed tomography after four doses of nivolumab. A total of 45 patients were included: 25 received 3 mg/kg (SD-NIV) and 20 received a flat dose of 40 mg (NIV40). The mean dose of nivolumab administered once in 2 weeks was 2.9 mg/kg (stable disease 0.31) in the SD-NIV group compared with 0.6 mg/kg (stable disease 0.10) in the NIV40 group (<i>P</i> < .001). Responses after four doses of nivolumab were similar in the SD-NIV versus NIV40 group: complete response (48% <i>v</i> 50%), partial response (12% <i>v</i> 10%), stable disease (20% <i>v</i> 20%), and progressive disease (20% <i>v</i> 20%; <i>P</i> = .997). Immune-related adverse effects were similar in the two groups (12% <i>v</i> 10%; <i>P</i> = .790). Two-year event-free survival (EFS) of the whole cohort treated with nivolumab with SD-NIV and NIV40 was 47% and 49.5%, respectively (<i>P</i> = .788). Twenty-two of the 45 patients underwent stem cell transplant (11 from each group), with a 2-year EFS of 90.1% versus 81.8% (<i>P</i> = .545) in the SD-NIV and NIV40 groups, respectively. Despite the inherent limitations of a retrospective analysis, the data suggests that nivolumab demonstrates biologic efficacy at doses as low as 0.6 mg/kg. Prospective trials comparing different dosing strategies are clearly warranted; such studies may facilitate approval of biologically active and cost-effective regimens, thereby broadening access to checkpoint inhibitors.