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. 2025 Apr 30;9(5):e70126.
doi: 10.1002/hem3.70126. eCollection 2025 May.

Nivolumab plus ifosfamide, carboplatin, and etoposide are a highly effective first salvage regimen in high-risk relapsed/refractory Hodgkin lymphoma

Matthew Mei  1 , Joycelynne Palmer  2 , Hun Ju Lee  3 , Iris Isufi  4 , Robert Chen  5 , Ni-Chun Tsai  2 , Saro Armenian  6 , James Godfrey  1 , Joo Y Song  7 , John H Baird  1 , Swetha Thiruvengadam  1 , Yazeed Samara  8 , Jessica Flores  9 , Lacolle Peters  9 , Steven Rosen  1 , Larry Kwak  1 , Stephen J Forman  1 , Alex F Herrera  1
Affiliations

Nivolumab plus ifosfamide, carboplatin, and etoposide are a highly effective first salvage regimen in high-risk relapsed/refractory Hodgkin lymphoma

Matthew Mei et al. Hemasphere. .

Abstract

Nivolumab is an anti-PD-1 antibody that is effective in patients with relapsed/refractory (RR) classic Hodgkin lymphoma (cHL). We previously showed PET-adapted sequential nivolumab ± ifosfamide, carboplatin, and etoposide (ICE) chemotherapy as the first salvage in RR cHL was a safe and effective bridge to autologous stem cell transplant (ASCT) (cohort A). We then tested a non-PET-adapted schema where all patients received nivolumab + ICE (cohort B). In this study, we present results from cohort B. Patients with high-risk RR cHL after frontline treatment received 240 mg nivolumab followed by 2-3 cycles of NICE (240 mg nivolumab day 1, standard doses of ICE). High-risk disease was defined as having one of the following: primary refractory cHL, relapse within 1 year of completing frontline therapy, B symptoms at relapse, extranodal disease at relapse, or frontline brentuximab vedotin use. PET/CT was performed after nivolumab × 1 and NICE × 2. Responding patients (complete response [CR] or partial response) were intended to proceed to ASCT. The primary endpoint was CR rate per 2014 Lugano classification. A total of 35 patients were enrolled, all of whom were evaluable for safety and efficacy. Overall response rate and CR were 100% and 86%, respectively; 2-year progression-free survival (PFS) and overall survival (OS) were 88% and 100%, respectively. Thirty-two patients proceeded to ASCT directly after NICE; 2-year post-ASCT PFS and OS were 94% and 100%, respectively. Immune-related toxicities were all grades 1-2, and no patient discontinued treatment for toxicity. Nivolumab/NICE is a highly effective salvage regimen and bridges patients effectively to ASCT.

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Conflict of interest statement

A. F. H. reports research funding from BMS, Merck, Genentech, Inc/F. Hoffmann‐La Roche Ltd, Gilead Sciences, SeaGen, AstraZeneca, and ADC Therapeutics, and consultancy for BMS, Merck, Genentech, Inc/F. Hoffmann‐La Roche Ltd, Kite Pharma/Gilead, SeaGen, Karyopharm, Takeda, Tubulis, AstraZeneca, Genmab, ADC Therapeutics, and Regeneron. M. G. M. reports research funding from BMS, Genentech, BeiGene, and Incyte; consultancy for Novartis, SeaGen, CTI, ADC therapeutics, AstraZeneca, and Synthekine; and speakers' bureau with SeaGen and Incyte. S. K. reports research funding from Genentech, ADC Therapeutics, Genmab, AbbVie, and Ipsen, and cosnultancy for Ipsen, Kite, and AbbVie. The remaining authors declare no competing financial interests.

Figures

Figure 1
Figure 1
Survival outcomes. (A) PFS in patients who proceeded directly to ASCT after protocol therapy; (B) PFS in all evaluable patients; and (C) OS in all treated patients. ASCT, autologous hematopoietic cell transplantation; OS, overall survival; PFS, progression‐free survival.
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