Year: 2019
Type: article
Abstract: Introduction: Extranodal Natural killer/T-cell lymphoma, nasal type (ENKTCL) is a rare and aggressive subtype of peripheral T cell lymphoma strongly associated with Epstein-Barr virus. The use of Asparaginase in the last ten years has significantly improved the prognosis of this lymphoma. Although 60% of these patients are now cured with this regimen even while relapsing, some are however primary refractory or relapse early. NK/T lymphomagenesis is characterized by immune resistance with inefficient immune response directed against EBV-positive tumor cells. The PD-1 (programmed cell death protein 1) / PD-L1 (programmed cell death protein ligand 1) axis is thought to play a role in this process by averting effector T-cell targeting. PD-1/PD-L1 blockade represents therefore a relevant therapeutic strategy in relapsed/ refractory ENKTCL patients and has already demonstrated efficacy in very few cases. Methods: We report here the outcome of 13 ENKTCL patients treated with PD-1 inhibitors between March 2017 and August 2018. All patients presented with relapsed or refractory lymphoma failing Asparaginase regimens. Four out of these patients have been treated in the frame of the AcSé Pembrolizumab UNICANCER Immunotherapy Group protocol. Results: Median age was 44 years (range, 20-73) and sex ratio (M/F) was 1.6. Five patients presented at diagnosis with localized disease and 8 had advanced-stage disease. PINK score was low in 2, intermediate in 7 and high in 4 patients. All patients have been previously treated by at least one line of chemotherapy containing Asparaginase. In most cases (12/13), patients have received pembroluzimab as PD-1 inhibitor and a median of 5 (range, 1-14) cycles were administered. Four patients (31%) have responded to pembroluzimab durably (3 complete response and one partial response) with a median follow up of 12.5 months (range, 7.7-19). One patient achieved partial response but relapsed, 7 patients (53%) progressed and one was unevaluable. Progression-free survival and overall survival at 12 months were 39% and 46% respectively. Treatment-related adverse events of grade ≥3 were observed in 3 patients (cytopenia in 2 cases and cytokine release syndrome in one case). PD-L1 immunohistochemical data are currently available in 4 patients (1 complete response, 1 partial response and 2 progressions). In all patients, no PD-L1 expression was detected in ENKTCL cells, suggesting that response to anti-PD1 antibodies is not correlated to PD-L1 expression in the tumor. Conclusions: To our knowledge, this is the largest reported series of ENKTCL patients treated with PD-1 inhibitors. Our findings indicate that PD-1 blockade represents a potent strategy for a subset of relapsed/refractory ENKTCL patients failing Asparaginase regimens. However, further immunohistochemical and molecular studies are warranted to identify predictive biomarkers of response to immune checkpoints inhibitors in order to improve patient selection. Keywords: non-Hodgkin lymphoma (NHL); PD-1; Pembrolizumab. Disclosures: Salles, G: Honoraria: from BMS and Merck to participate to advisory boards and symposiums.
Source: Hematological Oncology
DOI: 10.1002/hon.83_2630
Institutions: Institut des Maladies Génétiques Imagine, Centre Hospitalier Universitaire de Limoges, Hôpital Necker-Enfants Malades, Assistance Publique – Hôpitaux de Paris, The Lymphoma Academic Research Organisation, Centre Hospitalier Universitaire de Rennes, Centre Hospitalier Universitaire d'Angers, Hôpital Saint-Antoine, Centre hospitalier universitaire d'Orléans, Centre Hospitalier Universitaire Henri-Mondor, Hôpitaux Universitaires Henri-Mondor, Institut Paoli-Calmettes, Centre Hospitalier Annecy Genevois, Kyoto University, Hôpital Lyon Sud
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2953135272