Abstract 2656: Polatuzumab vedotin significantly enhances in vitro cell death and overall survival against CD79b+ Burkitt lymphoma (BL)/primary mediastinal large B-cell lymphoma (PMBL) NSG xenograft mice

Abstract

Abstract Background: Mature B-NHL, including Burkitt lymphoma and primary mediastinal large B cell lymphoma express CD79b+ and have an excellent prognosis with chemo-immunotherapy (Cairo et al Blood, 2007, Gerrard/Cairo et al. Blood, 2013). However, a subset of patients with relapsed/refractory mature B-NHL has chemoimmunotherapy resistant disease a dismal prognosis (≤ 10% 5 years, EFS) (Cairo et al. JCO, 2012). The antibody drug conjugates (Polatuzumab Vedotin, PV) has demonstrated significant preclinical activity against indolent CD79b+NHL (Polson et al.Can. Res. 2009). More recently PV has been safe and well tolerated in adult with CD79b refractory CLL (Palanca-Wessels et al. Lancet Oncol, 2014) but its preclinical activity against mature B-NHL (BL/PMBL) is unknown. Objective: To determine the efficacy of the PV against CD79b+ PMBL and rituximab (RTX) sensitive/resistant BL tumor cell lines in-vitro and in-vivo. Design/Methods: Raji/Raji4RH (BL, provided by M. Barth, Roswell Park Cancer Institute) and Karpas1106P and MedB-1(PMBL) were cultured in 10-20% RPMI. Tumor cells were incubated with hu anti-CD79b-vc-MMAE, and/or anti-CD79b, MMAE or huIgG1 (generously supplied by Genentech Inc.) for 24 hrs. Cell death was evaluated by staining with annexin V/7AAD and analyzed by flow cytometry, n=3. Six to 8 week old female NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ), were divided into 5 groups: PBS only (control), isotype control (IgG), PV (5mg/kg), anti-CD79b mAb (5 mg/kg) and MMAE (5 mg/kg). Mice were xenografted with intravenous injections of Luc+ Raji/Raji4RH and Karpas1106P cells as we have previously demonstrated (Awasthi/Cairo et al, BJH, 2015). Mice were treated twice a week for 6 weeks. Tumor burden was monitored by IVIS spectrum system. Results: Anti-CD79b-vc-MMAE compared to anti-CD79b Ab or IgG1 Ab alone (10µg/ml, 24hrs), significantly enhanced cell death in Raji, 47.2±1.3% vs 29.1±6.0% vs. 28.2±4.3%, (p=0.0008 and p=0.00006), Raji4RH, 29.8±9.1% vs 25.4±3.9% vs. 18.0±8.2% (p=NS and p=0.03), Karpas1106P, 46.8±5.3% vs 33.8±3.5% vs. 26.2±0.4% (p=0.02 and 0.006) and MedB-1, 47.4±2.2% vs 27.6±2.4% vs. 23.9±1.7% (p=0.002 and 0.0001), respectively. Further, median survival time in mice receiving 5 mg/kg of PV was significantly increased when compared to mice receiving 5 mg/kg of anti-CD79b Ab or isotype control in Raji, Raji4RH and Karpas1106P (35.5 vs.17 vs. 19.5 days, p=0.0001, 0.0003, 50 vs. 18 vs. 18.5 days and 150 vs 89 vs 64 days, p=0.03 ,0.003, respectively) Conclusions: Our preliminary data indicates that PV significantly enhances cell death in RTX sensitive/ resistant BL and PMBL compared to CD79b Ab or isotype control. Furthermore, PV significantly increased survival in BL and PMBL NSG xenografts Citation Format: Aradhana A. Tiwari, Janet Ayello, Christeen Azmy, Carmella van de Ven, Mitchell S. Cairo. Polatuzumab vedotin significantly enhances in vitro cell death and overall survival against CD79b+ Burkitt lymphoma (BL)/primary mediastinal large B-cell lymphoma (PMBL) NSG xenograft mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2656. doi:10.1158/1538-7445.AM2017-2656