Abstract 2381: Blinatumomab enhanced anti-tumor activity against rituximab sensitive and resistant Burkitt Lymphoma (BL) and Primary Mediastinal B-cell Lymphoma (PMBL)
Authors: Tiwari Aradhana Awasthi , Edani Dina , Ayello Janet , Cairo Mitchell S. 
Published: August 2019

Background: Childhood, Adolescent and Young Adult (CAYA) B-NHL represents the third most common malignancies in children under the age of 15yrs (Hochberg/Cairo et al, BJH 2009; Miles/Cairo, BJH. 2012).The prognosis of mature-B-NHL (which include BL/PMBL) has significantly improved over the last 40 years through the use of short and intense multi-agent chemo-immunotherapy, however; a subset of patients with relapsed/refractory disease has chemoimmunotherapy resistant disease and a dismal prognosis (≤ 20% 5 yr. EFS, Cairo et al.Blood. 2007; Cairo et al. JCO.2012, Goldman/Cairo et al. Leukemia, 2013, Gerrard/Cairo et al. Blood. 2013). It is therefore critical to investigate and develop targeted translational strategies in BL/PMBL to reduce acute morbidities, decrease late effects, and provide new options for those with recurrent disease. Blinatumomab, targeting CD19, has demonstrated encouraging clinical activity against pre-B-ALL (Topp et al, Leukemia, 2018) and highly expressed in BL/PMBL.

Objectives: To determine in-vitro activity of blinatumomab against rituximab sensitive/resistant BL and PMBL cell lines.

Methods: BL; Raji, Raji-4RH, and PMBL: Karpas1106p/MedB-1 were cultured in RPMI with 10 or 20% FBS. Tumor cells were incubated with/without blinatumomab (generously supplied by Amgen) for 4 hr. with T-cells. CD3+ isolated and expanded T-cells were used for cytotoxicity assay. Cytotoxicity was determined by DELFIA®cytotoxicity assay at 10:1 E: T ratio and cytokines secretion was measured by multiples ELISA kit. CD3+/CD107a+, granzyme b and perforin T-cell expression level were measured by flow-cytometry.

Results: Blinatumomab+T-cells compared to T-cells only elicited a significant increased cytotoxicity against, Raji 58.18±7.6% vs 27.3.81±11.2% (p=0.007), Raji-4RH 67.4±8.0% vs 27.6±2.5%, (p=0.004), Karpas1106p, 75.7±3.06 % vs. 17.86± 4.82% (p=0.003) and MedB1, 65.17±13.3% vs18.1±2.03%, respectively (p=0.05). Blinatumomab treated T-cells also increased IFN-γ secretion compared to IL2-T cells, Raji 1 (p=0.002) and Raji-4RH (p=0.02) respectively.

Furthermore, CD107a, granzyme b and perforin expression were significantly enhanced with blinatumomab treated/activated T-cells against; Raji (p=0.03, p=0.003 & p=0.009), Raji-4RH (p=0.03, p=0.02 & p=0.03) and Karpas1106p (p=0.006, p=0.03 & p=0.02) respectively.

Conclusion: Blinatumomab significantly enhances T-mediated in-vitro cytotoxicity and cytokine secretion against BL/PMBL. Further, blinatumomab treated and activated T-cells significantly enhanced CD107a, granzyme b and perforin expression. These preliminary studies demonstrate that BiTE (CD3/CD19) would be a novel agent to investigate as immunotherapy therapy in patients with relapse refectory BL/PMBL.

Citation Format: Aradhana Awasthi Tiwari, Dina Edani, Janet Ayello, Mitchell S. Cairo. Blinatumomab enhanced anti-tumor activity against rituximab sensitive and resistant Burkitt Lymphoma (BL) and Primary Mediastinal B-cell Lymphoma (PMBL) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2381.