Antibody Drug Conjugates (Anti-Cd79b-Vc-Mmae, Polatuzumab Vedotin) Exhibit Enhanced Cell Death Targeted To Cd79b+Burkitt Lymphoma (Bl) And Primary Mediastinal Large B-Cell Lymphoma (Pmbl)

Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LABackground: Mature B-NHL, including Burkitt lymphoma (BL) and primary mediastinal large B cell lymphoma (PMBL) express CD79b+ and have an excellent prognosis with chemo-immunotherapy (Cairo et al Blood, 2007,Goldman/Cairo et al. Leukemia, 2013, 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, Miles/Cairo et al. BJH, 2012). The anti-CD79b-vc-MMAE antibody drug conjugates (Polatuzumab Vedotin, PV) has demonstrated significant preclinical activity against indolent CD79b+NHL (Polson et. al.Can. Res. 2009, Dornan et al. Blood, 2009). More recently PV has been safe and well tolerated in adult with CD79b refractory NHL (Palanca-Wessels et al. Lancet oncol, 2015) but its preclinical activity against mature BL/PMBL is unknown.Objective: To determine the efficacy of ADC (anti-CD79b-vc-MMAE) against RTX sensitive/resistant CD79+ BL and PMBL tumor cell lines in-vitro.Methods: BL: Raji/Raji4RH (provided by M. Barth, Roswell Park Cancer Institute) and PMBL: Karpas1106p and MedB-1 were cultured in RPMI with 10 or 20% FBS. 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 cell proliferation was analyzed by alamar blue by flow-cytometry, n = 3.Results: Hu- anti -CD79b-vc-MMAE compared to hu anti-CD79b Ab or control hu IgG1 Ab alone (10μg/ml, 24hrs), significantly enhanced cell death (apoptosis) 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. Hu anti- CD79b-vc-MMAE also significantly reduced cell proliferation compared to hu anti- CD79b Ab or control hu anti -IgG1 Ab alone (20μg/ml, 24hrs). Raji, 56.1±5.1% vs 38.1±0.7% vs. 14.8±0.4% (p = 0.001 and p = 0.0008), Raji4RH, 53.4±5.4% vs 23.4±5.51% vs. 11.3±0.8% (p = 0.004 and 0.006), Karpas1106p, 46.4±0.3%vs 29.0±1.5% vs. 15.9±0.6% (p = 0.005 and 0.00007) and MedB-1, 47.2±7.5% vs 27.7±8.5% vs. 12.3±0.5% (p = 0.01 and p = 0.0005), respectively.Conclusion: Our preliminary data indicates that hu anti- CD79b-vc-MMAE significantly enhances cell death and reduced cell proliferation in sensitive/ RTX resistant CD79b+ BL and PMBL compared to CD79b Ab or isotype control IgG1 Ab alone. Hu anti- CD79b-vc-MMAE may be a novel agent to investigate as immunotherapeutic agent in patients with relapsed refractory CD79b+ BL and/or PMBL.Citation Format: Aradhana Awasthi Tiwari, Janet Ayello, Carmella van de Ven, Lisa Kurien, Matthew J. Barth, Mitchell S. Cairo. Antibody drug conjugates (anti-CD79b-vc-MMAE, Polatuzumab Vedotin) exhibit enhanced cell death targeted to CD79b+ Burkitt lymphoma (BL) and primary mediastinal large B-cell lymphoma (PMBL). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 579.