Dual-Targeted Antibody Offers Positive Outcomes for Non-Hodgkin Lymphoma

Non-Hodgkin Lymphoma: Non-Hodgkin LymphomaORLANDO—Treatment with the investigational drug called mosunetuzumab led to complete responses and durable remissions among patients with B-cell non-Hodgkin lymphoma (NHL) who had relapsed or failed to respond to a median of three prior therapies, according to data presented at the 2019 ASH Annual Meeting (Abstract 6). “When we approach unmet needs in medicine, we solve one and we create another,” noted lead author Stephen J. Schuster, MD, Director of the Lymphoma Program and Lymphoma Translational Research at Abramson Cancer Center, University of Pennsylvania. “CAR-T cells have been a major advance in the therapy of patients with refractory B-cell malignancies.Stephen J. Schuster, MD: Stephen J. Schuster, MD“We have had approval of two agents in the last 2 years,” he continued. “However, the two-thirds of patients who don't respond to CAR T-cell therapy are now our new unmet need.” To address this need, Schuster and his team are exploring the use of mosunetuzumab in these patients. “Mosunetuzumab is a bispecific antibody that binds to CD20 on B cells and malignant B cells, and CD3 on T cells,” he explained during a press conference. “In binding to the T cells, it is capable of inducing T-cell activation and, when engaged with the B cell, death of the target cell and eliminating those cells.” Methods & Results GO29781 is an open-label, multicenter, phase I/Ib, dose-escalation and expansion study of mosunetuzumab in relapsed/refractory B-cell NHL. Key objectives include best objective response rate (ORR) by revised International Working Group criteria, maximum tolerated dose, and tolerability. Data presented includes patients from Group B, who received the therapy with step-up dosing on days 1, 8, and 15 of cycle 1, and then as a fixed dose on day 1 of each subsequent 21-day cycle, according to the researchers. This data represents 270 patients with a median age of 62 from seven countries (U.S., Australia, Canada, Germany, South Korea, Spain, and United Kingdom). Study authors reported that 67 percent had fast-growing lymphomas. For 30 patients (11%), their cancer was resistant to or had returned after an initial response to CAR T-cell therapy. Disease progression occurred for 77 patients (29%) following a stem cell transplant. In terms of safety, 28.9 percent of patients treated with mosunetuzumab experienced cytokine-release syndrome (CRS), the majority of cases being grade 1 (20%). Among the patients who received prior CAR T-cell therapy, there was no significant difference in rates of CRS (26.7%), according to Schuster. Moderately severe neurologic events occurred in 4 percent of all patients. Among 124 patients with fast-growing lymphomas, 46 (37.1%) had objective responses and 24 (19.4%) reported complete remissions (CR). For patients with indolent lymphomas, 42 of 67 (62.7%) had objective responses while 29 of 67 (43.3%) had CRs. There was a 38.9 percent ORR (7 patients) and a 22.2 percent CR (4 patients) among patients who had prior CAR T-cell therapy. “What is important is that this is not an ongoing therapy forever,” Schuster said. “This is a therapy the patients receive until they're in remission then it's discontinued. Three-quarters of the patients that are in CR in this study are off therapy and being followed.” With a median follow-up of 6 months since first complete remission, researchers reported that 24 of 29 patients with slow-growing lymphomas who achieved CR remain free of disease. Comparatively, 17 of 24 patients (71%) with CRs in the fast-growing lymphoma group are still in remission. “Mosunetuzumab has favorable tolerability and durable efficacy in patients with heavily pre-treated R/R B-cell NHL, including CRs in patients with disease progression after CAR-T therapies. Preliminary data support the possibility for re-treatment with [this approach],” study authors concluded. ASH Abstract 6 Implications As a single agent, mosunetuzumab demonstrates a promising benefit-risk profile among patients with R/R B-cell lymphomas, Schuster said. “Unlike CAR T-cell therapy, mosunetuzumab is an off-the-shelf immunotherapy product that can be given to patients without having to genetically modify their T cells,” he noted, in a statement. “Mosunetuzumab generates long-lasting responses with a very tolerable safety profile in patients with B-cell non-Hodgkin lymphomas for whom multiple prior treatments have failed and whose prognosis is poor. Of particular interest, we are seeing durable complete remissions in patients whose lymphomas progressed after CAR-T. “Larger, randomized trials are needed to further confirm these promising data and determine whether the treatment benefit of mosunetuzumab is enhanced when it is used earlier in the course of lymphoma therapy or in combination with other agents.” Patients are now being enrolled to study a higher dose of mosunetuzumab. “There are a lot of studies going on and I think the future of this drug and this off-the-shelf approach to exploiting cellular therapy is the direction that we will be pursuing in the future,” Schuster concluded. Catlin Nalley is a contributing writer.

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