Contemporary outcomes of salvage high-dose chemotherapy in advanced germ cell tumors: an analysis of the cellular therapy and immunobiology working party of the EBMT registry

Background The optimal salvage therapy for relapsed germ cell tumors (GCTs) remains undefined and the optimal timing for high-dose chemotherapy (HD-CT) is unclear. We analyzed data from the European Society for Blood and Marrow Transplantation registry to evaluate contemporary outcomes in patients treated with HD-CT across salvage lines. Patients and methods We extracted data of adult males with GCTs (excluding mediastinal primary) who received one or more courses of HD-CT with carboplatin and etoposide between 2000 and 2022. Patients treated within 3 months from diagnosis were excluded, as this was considered upfront therapy. Time from diagnosis to first HD-CT (TT) was categorized in 3-6, 6-12, and >12 months. A Cox model with restricted cubic splines was used to evaluate the nonlinear effect of TT on survival. Results Data from a total of 2204 patients were analyzed. Histology was available for 1074, of whom 69% had nonseminoma. Among 969 patients with primary site information, 69% had testicular GCT. International Prognostic Factors Study Group (IPFSG) categories were available for 500 patients: 17% very high, 38% high, 31% intermediate, 10% low, and 3.6% very low risk. TT was 3-6 months for 280 (13%), 6-12 months for 831 (38%), and >12 months for 1093 (50%). Of the patients, 1118 (51%) received three cycles of HD-CT. Median overall survival (OS) and progression-free survival (PFS) were 36.4 [95% confidence interval (CI) 30.3-58.7] and 9.9 months (95% CI 8.5-12.4), respectively. Spline analysis showed increasing hazard of progression and death with longer TT. No interaction was observed between TT and IPFSG risk for PFS ( P = 0.62), whereas a significant interaction was found for OS ( P = 0.04) in non–high-risk patients. Conclusions In the largest contemporary series of salvage HD-carboplatin–etoposide in GCTs, HD-CT was effective regardless of TT as a surrogate of salvage line, with a significant interaction in non–high-risk patients, suggesting a nonlinear association between HD-CT timing and OS.