RESUMO
ABSTRACT: Lymphodepletion (LD) is an integral component of chimeric antigen receptor T-cell (CART) immunotherapies. In this study, we compared the safety and efficacy of bendamustine (Benda) to standard fludarabine/cyclophosphamide (Flu/Cy) LD before CD19-directed, CD28-costimulated CART axicabtagene ciloleucel (axi-cel) for patients with large B-cell lymphoma (LBCL) and follicular lymphoma (FL). We analyzed 59 patients diagnosed with LBCL (n = 48) and FL (n = 11) consecutively treated with axi-cel at the University of Pennsylvania. We also analyzed serum samples for cytokine levels and metabolomic changes before and after LD. Flu/Cy and Benda demonstrated similar efficacy, with complete remission rates of 51.4% and 50.0% (P = .981), respectively, and similar progression-free and overall survivals. Any-grade cytokine-release syndrome occurred in 91.9% of patients receiving Flu/Cy vs 72.7% of patients receiving Benda (P = .048); any-grade neurotoxicity after Flu/Cy occurred in 45.9% of patients and after Benda in 18.2% of patients (P = .031). In addition, Flu/Cy was associated with a higher incidence of grade ≥3 neutropenia (100% vs 54.5%; P < .001), infections (78.4% vs 27.3%; P < .001), and neutropenic fever (78.4% vs 13.6%; P < .001). These results were confirmed both in patients with LBCL and those with FL. Mechanistically, patients with Flu/Cy had a greater increase in inflammatory cytokines associated with neurotoxicity and reduced levels of metabolites critical for redox balance and biosynthesis. This study suggests that Benda LD may be a safe alternative to Flu/Cy for CD28-based CART CD19-directed immunotherapy with similar efficacy and reduced toxicities. Benda is associated with reduced levels of inflammatory cytokines and increased anabolic metabolites.
Assuntos
Produtos Biológicos , Citocinas , Linfoma Folicular , Humanos , Cloridrato de Bendamustina/efeitos adversos , Antígenos CD28 , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , CiclofosfamidaRESUMO
OBJECTIVE: Primary extragonadal germ cell tumors are rare and their histogenetic origin is not clear. We describe two cases presenting as primary retroperitoneal germ cell tumors without clinical evidence of testicular tumor. METHODS: A 21 and 18 years-old patients presented retroperitoneal choriocarcinoma and yolk sac tumor, respectively. In both cases, testicular palpation was not suspicious for testicular cancer. Testicular ultrasound founded alterations in right testes. RESULTS: A right orchitectomy were performed and the final diagnostics were mature teratoma associated with intratubular malignant germ cell. CONCLUSION: Adult mature teratoma is infrequent and the retroperitoneal germ cell tumors should be considered to be metastases of a viable or burned-out testicular cancer.