Novel Antibody Elicits Complete Remissions in NHL After CAR Relapses

Anita Shaffer
Published: Saturday, Dec 07, 2019

Stephen J. Schuster, MD, director of the lymphoma program at Abramson Cancer Center at the University of Pennsylvania

Stephen J. Schuster, MD

Mosunetuzumab, a novel bispecific antibody, generated durable responses in patients with highly refractory non-Hodgkin lymphomas (NHLs), including complete remissions (CRs) in 22.2% of those who had previously received chimeric antigen receptor (CAR) T-cell therapy, according to study results presented at the 2019 American Society of Hematology Annual Meeting.1

The agent represents a promising therapy for patients whose disease has recurred after receiving CAR therapy or is progressing too rapidly to be treated with personalized gene therapy, said lead investigator Stephen J. Schuster, MD.

“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,” Schuster, director of the lymphoma program at Abramson Cancer Center at the University of Pennsylvania (UPenn) in Philadelphia, said in a statement.

The therapy exhibited a tolerable safety profile, with mostly low-grade occurrences of cytokine release syndrome (CRS) and neurological adverse events (AEs), said Schuster, who is also the Robert and Margarita Louis-Dreyfus Professor in Chronic Lymphocytic Leukemia and Lymphoma Clinical Care and Research at UPenn.

Mosunetuzumab is a humanized antibody that contains 2 antigen-recognition sites: CD3, a T-cell surface antigen, and CD20, a tumor-associated antigen exclusively expressed on B cells.2 “In binding to the T cells, it’s capable of inducing T-cell activation and, when engaged with a B cell, it will cause a death of the target cell and eliminate those cells,” Schuster said at a press briefing.

The 2 FDA-approved CAR therapies, tisagenlecleucel (Kymriah) and axicabtagene ciloleucel (Yescarta), are CD19-directed genetically modified autologous T-cell immunotherapies. Although CAR agents represent a significant advance in treating refractory B-cell malignancies, Schuster said, two-thirds of patients with lymphomas do not respond.

He also said the process of producing and obtaining insurance approval for CAR therapy delays treatment by several weeks. “A month or 2 months doesn’t sound long but it’s an eternity when you have a patient with a very fast-paced disease,” he said.

“To be able to use the cellular immunotherapeutic approach [with mosunetuzumab] rapidly in patients who need this approach because traditional immunochemotherapy is no longer working is, I think, a very important aspect,” Schuster added. An off-the-shelf product that has alternative B-cell targets to CD19, which the approved CAR T cell products address, is necessary.”

Study Findings Detailed

At the briefing, Schuster reported efficacy results for 191 evaluable patients treated with mosunetuzumab monotherapy during the ongoing phase I/Ib dose-escalation GO29781 study (NCT02500407) in late-line relapsed/refractory B-cell NHLs. The data are from Group B of the study, in which patients received mosunetuzumab intravenously with stepped-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 (maximum 17 cycles).

Among 124 patients with aggressive NHL, the objective response rate (ORR) was 37.1% (n = 46), including 19.4% (n = 24) with a CR, according to pooled data from participants who received mosunetuzumab at doses ranging from 2.8 mg to 40.5 mg. After a median follow-up of 6 months, 17 patients remain in CR.

In 67 participants with indolent NHL, the ORR was 62.7% (n = 42), including 43.3% (n = 29) with a CR, for dosing cohorts ranging from 2.8 mg to 13.5 mg. Twenty-four patients remain in CR up to 26 months after initial treatment.

Notably, patients who previously received CAR T-cell therapy also responded to mosunetuzumab. Among 18 evaluable patients in this cohort, the ORR was 38.9% (n = 7), including a 22.2% CR rate (n = 4). Investigators also observed an expansion of lymphocytes, including residual CAR T cells in 2 of 8 patients, and CRs with and without CAR T-cell expansions.

Schuster described a 58-year-old woman with relapsed/refractory follicular lymphoma (FL) who had 8 prior lines of systemic treatment that included CD19-directed CAR T-cell therapy. The patient achieved a CR after 3 cycles of mosunetuzumab therapy and remains in CR after more than 8 months.

“This not an ongoing therapy forever,” Schuster said. “This is a therapy that patients receive until they’re in remission and then it’s discontinued. Three-quarters of the remission patients are off therapy.”

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