High-dose chemotherapy (HDCT) and peripheral-blood stem cell transplant (PBSCT) in patients age 40 or older with relapsed metastatic germ-cell tumors (mGCT).

Abstract

e17054 Background: HDCT plus PBSCT is effective salvage therapy for relapsed mGCT but has potential toxicity. Historically, age ≥ 40 years has been associated with greater toxicity and worse outcomes. Methods: 445 consecutive pts with relapsed mGCT were treated with HDCT and PBSCT with tandem cycles at Indiana University from between 2004-2017 per our institutional regimen ( N Engl J Med 2007; 357:340-8). Kaplan-Meier methods and log-rank tests were used for progression free survival (PFS) analysis. Results: 329 pts were age < 40 while 116 pts were age≥40 and HDCT was being used as 2nd line in 85% and 79%, respectively. Median follow-up time was 42.5 months (range 0.3-173.4). Pulmonary metastasis was more frequent in the age < 40 group (66% vs. 41%, P < 0.001). Patients age≥40 were more likely to have seminoma (45% vs. 14%, P < 0.001), were more likely not platinum refractory (80% vs. 63%, P = 0.0010), and were less likely to complete 2 planned tandem cycles of HDCT (86% vs. 93%, P = 0.03). Grade 3 or higher toxicities were similar between either cohort, except for greater pulmonary toxicity in age≥40 group (8% vs. 2%, P = 0.02). Treatment-related mortality was similar between both age groups: 10 patients (3%) in age < 40 and 4 patients (3.5%) in age≥40 group died from complications of HDCT. 2-year PFS for age < 40 vs. age ≥ 40 was 58.7% vs. 59.6% (P = 0.76) and 2-year OS was 63.9% vs. 61.5% (P = 0.93). When evaluating patients with pure seminoma: 2- year OS for age < 40 vs. 40-50 vs. ≥ 50 was 100% vs 90.3%, vs 81.4%, respectively (P = 0.09). For patients with non-seminoma: 2-year OS was 58.1% vs. 37.1% vs. 54.2%, respectively (P = 0.01). In multivariable analysis for PFS: significant factors predicting worse outcomes included platinum refractory disease (HR = 1.55, P = 0.03), primary mediastinal non-seminoma (HR = 2.41, P = 0.03), not completing 2 cycles of HDCT (HR = 2.47, P = 0.01), and hCG > 1000 at initiation of HDCT (HR = 1.92, P < 0.001). Age was not a significant factor predicting worse outcomes. Conclusions: HDCT plus PBSCT is effective salvage therapy in pts age≥40 with relapsed mGCT. Patients age > 40 experience similar rates of toxicity and treatment-related mortality as those < 40 years of age.