Abstract 1537: Polatuzumab Vedotin alone or in-combination with anti-CD20 antibody significantly enhanced overall survival in xenografted NSG mice against rituximab sensitive and resistant Burkitt Lymphoma (BL) and Primary Mediastinal B-cell Lymphoma (PMBL)
Authors: Tiwari Aradhana Awasthi , Edani Dina , Ayello Janet , Klein Christian , Cairo Mitchell S. 
Published: August 2019

Background: Patients with relapsed or refractory B-cell Non-Hodgkin Lymphoma (B-NHL) have an unfavorable prognosis with few treatment options (Goldman/Cairo et al. Leukemia, 2013). It is therefore critical to investigate and to develop targeted translational strategies in BL/PMBL in order to reduce acute morbidities, decrease late effects, and provide new options for those with recurrent disease. Polatuzumab Vedotin (PV) has been demonstrated to possess significant preclinical activity against indolent CD79b+NHL (Polson et. al. Can. Res. 2009). We previously observed that obinutuzumab vs. rituximab (anti-CD20 mAb) significantly increased overall survival against xenografted NSG mice in BL (Awasthi/Cairo et al., BJH 2015). However, synergistic effects of PV with obinutuzumab against mature PMBL/BL are unknown.

Objective: To determine the efficacy of the PV alone or in-combination with rituximab/obinutuzumab against rituximab-sensitive/resistant BL (Raji & Raji4RH) and PMBL (Karpas1106P) cell lines.

Methods: Six to 8 week old female NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ), were xenografted with intravenous injections of Luc+ BL and PMBL cells. Mice were divided into following groups: PBS, isotype control, PV, anti-CD79B and MMAE (5mg/kg) and or/with obinutuzumab/RTX (20mg/kg) for 8 weeks with 106 ex.PBNK cells. Animals were monitored for tumor burden progression/regression and survival for up to 12-30 weeks via BLI using the IVIS spectrum system as previously described (Awasthi/Cairo et al BJH, 2015).

Results: The probability of OS in B-NHL xenografts NSG mice receiving PV alone was significantly increased compared to anti-CD79b or isotype control in Raji (35.5 vs.17 vs.19.5 days, p=0.0001, 0.0003), Raji4RH (50 vs.18 vs.18.5 days, p=0.0001, 0.0001) and Karpas1106P (150 vs 89 vs 64 days, p=0.03, 0.003), respectively. Furthermore, The probability of OS of B-NHL xenogrfats NSG mice receiving PV+obinutuzumab+NK significantly increased compared to PV+rituximab+NK in Raji (95.5 vs. 50.4 days, p=0.03 ) and Raji4RH (185 vs.47 days, p=0.05). Moreover, obinutuzumab+NK vs. rituximab+NK also significantly increased over all survival both in Raji (92.5 vs. 52 days, p=0.05) and Raji4RH (80.5 vs. 40.0 days, p=0.04) respectively.

Conclusion: Our preliminary data indicates that PV significantly increased overall survival in BL and PMBL NSG xenografts compared to anti-CD79b Ab alone. Furthermore, PV in combination with obinutuzumab+NK-cells significantly enhance improved OS in BL and PMBL NSG xenografts compared to obinutuzumab or PV alone.

Citation Format: Aradhana Awasthi Tiwari, Dina Edani, Janet Ayello, Christian Klein, Mitchell S. Cairo. Polatuzumab Vedotin alone or in-combination with anti-CD20 antibody significantly enhanced overall survival in xenografted NSG mice 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 1537.