Clinical characteristics and outcomes of adult lymphoma-associated hemophagocytic lymphohistiocytosis (HLH).

Abstract

e19526 Background: Lymphoma is a major cause of secondary HLH, a life-threatening hyperinflammatory syndrome due to immune dysregulation. This study examines the clinical and biological characteristics, management, and outcomes of patients with lymphoma and HLH. Methods: We retrospectively reviewed 44 adult patients with combined diagnoses of lymphoma and HLH at Memorial Sloan Kettering Cancer Center between June 2012 and September 2020. Overall survival (OS) was measured from the date of HLH diagnosis to the date of death or last follow-up. We evaluated the association of demographic, clinical, laboratory, and treatment variables on survival using log-rank tests and Cox proportional hazards model. Results: Of the 44 patients, 30 (68%) had T and NK-cell lymphoma, 12 (27%) had B-cell lymphoma, and 2 (5%) had Hodgkin lymphoma. All but one patient received HLH therapy including corticosteroids (95%), etoposide (68%), and intravenous immunoglobulin (18%), which was initiated within 1 day of diagnosis in 84% of cases. Twenty-five patients (57%) received lymphoma-directed therapy with etoposide (n = 17) or without etoposide (n = 8). Five of the 15 patients who underwent targeted tumor-sequencing of 400 genes harbored a TP53 mutation and all were refractory to frontline therapy, while 7 of 10 patients without TP53 mutation demonstrated initial treatment response ( p= 0.03). The median OS (mOS) of the entire cohort was 1.4 months, with a 30-day cumulative mortality incidence of 36.4%. Most deaths were attributed to relapsed or refractory HLH (n = 25/36, 69%) and lymphoma progression (n = 6/36, 17%). Patients with T/NK-cell lymphoma-associated HLH had a mOS of 1.4 months compared to 9.2 months in B-cell lymphomas ( p= 0.09). Ten patients (23%) were diagnosed with HLH within 60 days of their initial lymphoma diagnosis and had an improved prognosis (mOS 12.8 vs 1.3 months, p= 0.006). Treatment with etoposide, either alone or as part of a lymphoma-directed regimen, was associated with significantly improved survival (HR 0.48, 95% CI 0.24-0.96) whereas lymphoma-directed therapy with or without etoposide was not (HR 0.66, 95% CI 0.34-1.29). Significant predictors of mortality included age ≥60 years, non-white race, and concurrent infection during the hospitalization. Conclusions: In this large cohort from a single U.S. institution, there was a wide range of lymphoma subtypes associated with HLH. Despite increased disease recognition and prompt initiation of standard HLH and lymphoma-directed therapies, the prognosis remains very poor. Patients treated with etoposide had improved survival, highlighting the importance of controlling hyperinflammation during initial management. Notably, TP53 mutation was associated with primary refractory HLH. Future studies will aim to elucidate the pathophysiology of lymphoma-associated HLH in order to inform novel therapeutic approaches.