Which Pediatric cHL Patients Should Receive Transplant-Free Salvage Therapy?

Fludeoxyglucose-18 positron emission tomography (FDG-PET) response-guided salvage therapy may identify which pediatric patients with relapsed or refractory classic Hodgkin lymphoma (cHL) achieve excellent outcomes with transplant-free salvage therapy, according to the phase 3, non-randomized, EuroNet-PHL-R1 trial published in JAMA Oncology.

According to lead author Stephen Daw, MD, and colleagues, the current standard-of-care salvage therapy for relapsed or refractory cHL consists of consolidation high-dose chemotherapy (HDCT) and autologous stem cell transplant (aSCT). However, they investigated whether presalvage risk factors and FDG-PET response to reinduction chemotherapy “can guide escalation or de-escalation between HDCT/aSCT or transplant-free consolidation with radiotherapy to minimize toxic effects while maintaining high cure rates.”

The study included 118 patients younger than 18 years (median age, 16.3) with relapsed or refractory cHL across 68 sites in 13 European countries. The primary endpoint was 5-year event-free survival (EFS), and secondary endpoints included overall survival (OS) and progression-free survival (PFS). As the PFS and EFS were identical, the researchers only reported PFS data in the study.

Patients received alternating ifosfamide, etoposide, prednisolone (IEP) with adriamycin, bleomycin, vinblastine, dacarbazine (ABVD) as reinduction chemotherapy. Patients with low-risk cHL (n=59) received a second cycle of IEP, ABVD, and radiotherapy, while patients with high-risk cHL (n=59) received a second cycle of IEP and ABVD plus HDCT and aHSCT with or without radiotherapy.

For the overall cohort, the 5-year PFS was 71.3% (95% CI, 63.5%-80.1%), and the 5-year OS was 82.7% (95% CI, 75.8%-90.1%). Forty-one low-risk patients who received non-transplant salvage therapy had a 5-year PFS of 89.7% (95% CI, 80.7%-99.8%) and a 5-year OS of 97.4% (95% CI, 92.6%-100%). Eighteen low-risk patients who received HDCT and aHSCT had a 5-year PFS of 88.9% (95% CI, 75.5%-100%) and a 5-year OS of 100%. All 59 high-risk patients received HDCT and aHSCT, with a 5-year PFS of 53.3% (95% CI, 41.8%-67.9%) and a 5-year OS of 66.5% (95% CI, 54.9%-80.5%).

“In patients with relapsed/refractory classic Hodgkin lymphoma, risk stratification by FDG-PET response can identify patients that may be cured by chemoradiotherapy only, avoiding toxic effects of HDCT/aSCT [autologous HSCT] and reserving HDCT/aSCT [autologous HSCT] for patients with high-risk disease,” wrote Dr. Daw and colleagues.

Reference

Daw S, Claviez A, Kurch L, et al. Transplant and Nontransplant Salvage Therapy in Pediatric Relapsed or Refractory Hodgkin Lymphoma: The EuroNet-PHL-R1 Phase 3 Nonrandomized Clinical Trial. JAMA Oncol. 2025;11(3):258-267. doi:10.1001/jamaoncol.2024.5636