Effectiveness of Nivolumab with ICE Protocol in Relapsed or Refractory Hodgkin Lymphoma: A Single-Center Experience from Riyadh, Saudi Arabia
Authors: Alsakkaf Abdullah , Yahia Alaa Eldein , Alharbi Asim A , Alrajhi Abdullah M. , Alhalouly Tahani , Albtoosh Bilal , Alzahrani Kamal , Alnoamani Mohammed S , Alhumaid Muhned , Alshehri Hassan , Alshehry Nawal F , Motabi Ibraheem H , Marei Mohammed , Tailor Imran K 
Published: December 2024

Introduction:
Approximately 10% to 30% of patients with classical Hodgkin lymphoma (cHL) are refractory to initial therapy or relapse after standard therapies (Advani et al. 2021). Nivolumab (Nivo), a monoclonal antibody targeting programmed cell death protein 1 (PD-1), disrupts its interaction with ligands overexpressed by Reed-Sternberg cells, thereby restoring an effective antitumor immune response. Nivo has demonstrated tolerability and efficacy in patients with relapsed/refractory (RR) Hodgkin lymphoma (HL). In clinical evaluations, patients with RR HL treated with Nivo exhibited an overall response rate (ORR) of 73% and a complete response rate (CR) of 28% (Younes et al., 2016). Nivo has shown efficacy in the interim results from a phase 2 trial evaluating PET-adapted nivo alone or nivo + ICE (ifosfamide, carboplatin, etoposide) chemotherapy as first salvage therapy and bridge to autologous hematopoietic cell transplantation (AHCT) in RR HL (Mei et al., 2022). There is no standard salvage regimen in RR HL. Here, we report our experience using Nivolumab with ICE (NICE) Protocol without prior Nivolumab monotherapy in RR HL as first salvage and further treatment lines.
Methods:
Fourteen patients with biopsy-proven RR HL were included in a large tertiary center in Riyadh, Saudi Arabia. Eleven patients received concurrent nivo and ICE (240 mg nivo day 1, standard doses of ICE, administered inpatient or outpatient) from cycle 1 and more, with only three patients initially receiving nivo alone, followed by NICE. PET-CT was performed after cycle 3. Patients in complete response (CR) proceeded to autologous stem cell transplantation (ASCT); those not in CR received additional NICE cycles. The primary endpoint was the complete response rate according to 2014 Lugano classification, with progression-free survival (PFS) and overall survival (OS) as secondary endpoints.
Results:
All 14 patients were evaluable for response, with a median age of 27 years (range 17-52). After 3 cycles of treatment, the overall response rate (ORR) was 78.5%, with 43% achieving CR and 35.5% achieving partial response (PR). Seven (50%) patients proceeded to ASCT, There were no stem cell mobilization/collection failures and no relapses reported post-ASCT. Common adverse events included nausea, fatigue, anemia, and thrombocytopenia. One patient received NICE as fifth salvage line and died from ARDS post chemotherapy. At a median follow-up of 32.4 months, the 1-year PFS was 85% and OS was 93%. Six (42%) patients who received NICE as their first salvage therapy, 100% achieved a complete response (CR). The median overall survival (OS) for this group was 12.3 months. The median progression-free survival (PFS) for those who underwent Auto-SCT was 12.1 months and there were no relapses reported post Auto-SCT in this group. Eight (57%) patients who received NICE after their first salvage therapy, 12.5% achieved a CR. The median OS for this group was 30.0 months and a median PFS similar to the first group. Similarly, no relapses were reported post Auto-SCT.
Conclusion:
Nivo plus ICE is a well-tolerated and effective salvage therapy in RR HL, achieving high CR rates and facilitating ASCT. Best results are seen when given as first salvage similar to other studies. This comprehensive analysis highlights the effectiveness of Nivolumab combined with ICE, with substantial CR rates, improved PFS and OS, and no reported relapses post-ASCT. Randomised trials needed to establish best salvage regimen for these group of patients and further follow-up is required to evaluate long-term outcomes.