RESUMO
Given the limited treatment options for relapsed lymphoma post-allogeneic hematopoietic cell transplantation (post-allo-HCT) and the success of programmed death 1 (PD-1) blockade in classical Hodgkin lymphoma (cHL) patients, anti-PD-1 monoclonal antibodies (mAbs) are increasingly being used off-label after allo-HCT. To characterize the safety and efficacy of PD-1 blockade in this setting, we conducted a multicenter retrospective analysis of 31 lymphoma patients receiving anti-PD-1 mAbs for relapse post-allo-HCT. Twenty-nine (94%) patients had cHL and 27 had ≥1 salvage therapy post-allo-HCT and prior to anti-PD-1 treatment. Median follow-up was 428 days (range, 133-833) after the first dose of anti-PD-1. Overall response rate was 77% (15 complete responses and 8 partial responses) in 30 evaluable patients. At last follow-up, 11 of 31 patients progressed and 21 of 31 (68%) remain alive, with 8 (26%) deaths related to new-onset graft-versus-host disease (GVHD) after anti-PD-1. Seventeen (55%) patients developed treatment-emergent GVHD after initiation of anti-PD-1 (6 acute, 4 overlap, and 7 chronic), with onset after a median of 1, 2, and 2 doses, respectively. GVHD severity was grade III-IV acute or severe chronic in 9 patients. Only 2 of these 17 patients achieved complete response to GVHD treatment, and 14 of 17 required ≥2 systemic therapies. In conclusion, PD-1 blockade in relapsed cHL allo-HCT patients appears to be highly efficacious but frequently complicated by rapid onset of severe and treatment-refractory GVHD. PD-1 blockade post-allo-HCT should be studied further but cannot be recommended for routine use outside of a clinical trial.
Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Doença Enxerto-Hospedeiro/induzido quimicamente , Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/terapia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos/uso terapêutico , Feminino , Expressão Gênica , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/patologia , Doença de Hodgkin/imunologia , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Nivolumabe , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/imunologia , Indução de Remissão , Estudos Retrospectivos , Terapia de Salvação/métodos , Análise de Sobrevida , Condicionamento Pré-Transplante , Transplante Homólogo , Resultado do TratamentoRESUMO
Epstein-Barr virus (EBV)-encoded RNAs (EBER) in tumor tissue and cell-free plasma EBV-DNA (pEBVd) are detected in EBV-associated lymphomas. Studies have suggested that EBER+ peripheral T-cell lymphomas (PTCL) have worse prognosis but the role of EBV in these neoplasms remains unclear. pEBVd is quantitative and more easily amenable to standardization than EBER, but frequency of pEBVd detection, clinical impact and agreement with EBER status in PTCL are unknown. We retrospectively assessed frequency of detectable pre-treatment pEBVd, presence of EBER in tumor tissue, and outcomes in 61 of 135 EBV-assessable PTCL patients. Fifteen of 61 patients (24.5%, 95% CI: 14-37%) were pre-treatment pEBVd+, with no significant differences in baseline characteristics or treatment between pEBVd+ and pEBVd- patients. EBER-ISH was performed on 10 pEBVd+ and 35 pEBVd- tumors. All 10 pEBVd+ patients were EBER+, but 9 pEBVd- patients were also EBER+. With median follow up of 24 months (range 1-96), overall survival (OS) was shorter in pEBVd+ compared to pEBVd- patients (13 vs. 72 months; p = 0.04). In our retrospective study, pre-treatment pEBVd was elevated in 25% of PTCL patients, was highly specific for EBER+ tumors, and was associated with shorter survival. pEBVd should be further explored as a prognostic variable and tumor biomarker in PTCL.