Ublituximab plus TGR-1202 in Heavily Pretreated and High-Risk CLL
Ublituximab is a chimeric anti-CD20 monoclonal antibody that has been glycoengineered to enhance affinity and demonstrate significantly greater antibody-dependent cellular cytotoxicity than rituximab (Le Garff-Tavernier M, et al. Leukemia. 2014;28:230-233). Monotherapy with ublituximab in patients with rituximab–relapsed/refractory CLL has been reported to result in a 43% ORR (O’Connor OA, et al. J Clin Oncol. 2014;32[15 suppl]. Abstract 8524). TGR-1202 is an oral PI3Kd inhibitor that is active in patients with relapsed/refractory hematologic malignancies (Burris HA, et al. Presented at the 19th Congress of the European Hematology Association. Abstract P250). Ublituximab and TGR-1201 have shown synergistic activity in vitro, which prompted Lunning and colleagues to conduct a phase 1 trial to evaluate the safety and efficacy of this combination in patients with heavily pretreated relapsed/refractory CLL. They reported their results at ASH 2014 (Blood. 2014;124. Abstract 801).
As of the time of this report, 8 patients with relapsed/refractory CLL and with a median of 3 previous therapies had been accrued and evaluable for safety; 5 patients were evaluable for efficacy. The AEs have been manageable, with day-1 infusion reactions being the most common treatment-related event, followed by neutropenia, diarrhea, and nausea. Of the 5 patients with relapsed/refractory CLL who were evaluable for efficacy, 4 (80%) had a partial remission (PR), including 2 patients with del17p/del11q. These preliminary data suggest that the combination of ublituximab and TGR-1202 is well-tolerated with early signs of clinical activity in this heavily pretreated, high-risk patient population. Further testing of this regimen is warranted.