Complete Remission After First-Line Radio Plus Chemotherapy Is Enough to Improve Survival in Extra Nodal NK/T Cell lymphoma
Authors: Chauchet Adrien , Michallet Anne-Sophie , Berger Francoise , Bedgedjian Isabelle , Deconinck Eric , Sebban Catherine , Antal Daciana , Orfeuvre Hubert , Corront Bernadette , Petrella Tony , Hacini Maya , Bouteloup Marie , Salles Gilles Andre , Coiffier Bertrand 
Published: October 2019

Abstract
Abstract 2679
Extranodal nasal type NK/T-cell lymphoma (ENKTL) is a rare and severe disease, more frequent in Asia and South America. Previous studies showed that the 5-year overall survival (OS) rate was less than 40%, with a progression occurrence within 2 years. The early use of radiotherapy sequentially may cure approximately half of the patients with localized disease. In most patients with advanced disease (stage III/IV), the clinical course is highly aggressive with frequent chemotherapy resistance and a poor prognosis. CHOP-based therapy is frequently used and was associated with poor outcome. Considering the rarity of this lymphoma in Europe, we conducted this retrospective study that represents one of the largest studies of NK/T cell lymphoma 'nasal type'. Between January 1989 and September 2010, 36 patients were recruited with a median age of 49 years (22 to 80). 80% the patients was classified as upper aerodigestive tract NK/T-cell lymphoma (UNKTL) and 20% as extra-upper aerodigestive tract NK/T-cell lymphoma (EUNKTL). 72% of UNKTL patients had a local invasiveness superior to T3. 10 (28%) patients were in stage I, 6 (17%) in stage II and 20 (55%) in stage IV. Most frequent symptoms at diagnosis were obstructive symptomatology, epistaxis or cervical lymphadenopathy. 19 (53%) were in low risk versus 17 (47%) in high risk according to the Korean prognostic index. Chemotherapy (CT) alone was the primary treatment for advanced stage (84% CT and 10% CT+ radiotherapy (RT)) with 82% of patients receiving anthracyclin-based regimen. For the early stage, 50% of patients have received the combination CT plus RT and 50% CT. In the CT group, there was no statistical difference (p=0.77) in the percentage of CR according to the type of regimen. Complete response (CR) was observed in 48% of patient while the other 52% were in less than partial response (PR) or in progressive disease (PD) at the end of treatment. The CR rate was improved with the combination CT+RT (90%) versus 33% with CT alone (p<0,0001). For patients with UNKTL, only 50% of CR was obtained with CT, the combination CT+RT improved it to 90%. For patients with EUNKTL, all patients received an anthracyclin-based regimen with 43% of CR rate. For patients with early stage (I-II), 37% of CR was observed with CT versus 100% with CT+RT For the stage III or IV, the combination CT+ RT statistically improved the CR rate when compare to the CT strategy (p=0,014). Five years OS and PFS rates were 39% and 33% respectively. Gender, B symptoms, disease stage, LDH, IPI, PIT, Korean T/NK lymphoma score, and quality of response (CR versus no CR) were found to be significant factors on OS and PFS in univariate analyses. Extended stage of disease, local invasiveness, high level of LDH and high IPI, PIT or Korean T/NK lymphoma prognostic index were associated with poor survival. The quality of response was significantly associated to survival with 80% of OS at 5 years for the patients in CR versus no survey for patients with progressive disease (p<0,01). The best treatment strategy was the combination of CT+RT with a statistically significant difference in terms of OS and PFS at 5 years (p=0,013). The PFS was significantly longer for patients treated with RT+CT (70% vs 20% for CT, p=0,022).
The early use of radiotherapy concomitantly or sequentially with chemotherapy improves the outcome of patients, especially in localized disease but still with aggressive forms in this study. We confirm than quality of initial response is the most important factor for the 5 years overall survival. We think Korean T/NK lymphoma prognostic index to be probably more interesting than IPI score to distinguish high risk group and could be the most appropriate prognostic score for NK/T lymphoma nasal type. Finally, the use of agent like asparaginase in first line should be considered for patients with disseminated disease; this has to be evaluated in prospective trials in order to improve the survival in this disease.

Disclosures:
Salles: Roche and/or Genetech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genzyme: Membership on an entity's Board of Directors or advisory committees; Calistoga/Gilead: Membership on an entity's Board of Directors or advisory committees.