Mosunetuzumab Induces Complete Remissions in NHL After CAR T-Cell Therapy Relapse

A novel, off-the-shelf bispecific antibody could serve as a new treatment option for patients with non-Hodgkin lymphoma who don’t respond to CAR T-cell therapy.

A novel bispecific antibody demonstrated durable complete responses in patients with relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL), including those who had relapsed after chimeric antigen receptor (CAR) T-cell therapy, according to data presented at the American Society of Hematology (ASH) Annual Meeting and Exposition.

Mosunetuzumab, a fully humanized immunoglobulin G1 (IgG1) bispecific antibody targeting both CD3 and CD20, was evaluated in patients with R/R NHL, including those who previously received CAR T-cell therapy.

“When we approach unmet needs in medicine, we solve one and we create another,” lead author Stephen J Schuster, MD, said in a press briefing about the findings. CAR T cells have been a major advance in the therapy of patients with refractory B-cell malignancies, successfully treating one-third of patients. However, the other two-thirds of patients who don’t respond to CAR T-cell therapy represent a new unmet need. In addition, new treatment options are needed for patients whose disease is progressing quickly and cannot wait for CAR T cell manufacturing.

In a media preview prior to the meeting, Robert A. Brodsky, MD, secretary of ASH, emphasized the importance of the findings, noting that mosunetuzumab addresses these obstacles.

“It is an off-the-shelf product,” Brodsky explained in the briefing. “It completely gets around the problem of time to generate the CAR T-cell product.”

At the meeting, study results were presented from the ongoing phase 1/1b dose escalation study. Data was presented from Group B, in which mosunetuzumab is administered 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. The updated results include data from 270 patients with R/R NHL, which includes 30 patients with prior CAR T-cell therapy.

Overall, mosunetuzumab demonstrated durable complete response (CR) in both aggressive and indolent NHL, as well as promising CR rates in late-line diffuse large B-cell lymphoma/transformed follicular lymphoma (FL) and FL and in high-risk subsets. Pooled data from 2.8 mg to 40 mg cohorts showed an ORR of 37.1% and CR rate of 19.4% in patients with aggressive lymphoma. In those with indolent NHL, data from the 2.8 mg to 13.5 mg cohorts showed an ORR of 62.7% and a CR rate of 43.3%.

In patients with prior CAR T-cell therapy, objective responses without unexpected toxicities were observed. Mosunetuzumab demonstrated a 38.9% ORR and a 22.2% CR rate in these patients, according to the data.

With a median follow-up of 6 months since first complete remission, 83% of patients who achieved complete remissions of their slow-growing lymphomas and 71% of patients who achieved complete remissions of their fast-growing lymphomas remain free of disease.

“What I think is important is that this is not an ongoing therapy forever,” Schuster said. “This is a therapy patients receive until they’re in remission and it’s discontinued.”

Three-quarters of the patients in complete remission in this study are currently off therapy and being followed, according to Schuster.

Additionally, 4 patients in the study have been re-treated with mosunetuzumab. Three out of 4 of them responded to re-treatment, with 1 demonstrating a complete response.

Twenty-nine percent of patients in the study treated with mosunetuzumab experienced cytokine-release syndrome that was mostly mild. Four percent of patients experienced moderately severe neurologic adverse effects.

The results indicate that, as a single agent, mosunetuzumab exhibits a promising efficacy potential with acceptable risks, Schuster said. A study of higher dose mosunetuzumab is now enrolling patients. Schuster noted that long-term follow-up will help to better evaluate the durability of response data.

“There’s a lot of studies going on and I think the future for this drug and this approach, this off-the-shelf approach to exploiting cellular therapy, is the direction that we’ll be pursuing in the future,” Schuster concluded.

References

  • Schuster SJ, Bartlett NL, Assouline S, et al. Mosunetuzumab induces complete remissions in poor prognosis non-Hodgkin lymphoma patients, including those who are resistant to or relapsing after chimeric antigen receptor T-cell (CAR-T) therapies, and is active in treatment through lines [abstract 6]. Presented at: ASH Annual Meeting and Exposition. December 7-10, 2019. Orlando, Florida.