Efficacy and Safety Outcomes of CAR T-Cell Therapies in Patients with Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma Who Received Prior Treatment with Mosunetuzumab
Authors: Braun Adam , Schuster Stephen J. , Nastoupil Loretta , Bartlett Nancy L. , Shadman Mazyar , Kumar Anita , Tzachanis Dimitrios , Chihara Dai , Wu Mei , Wei Michael C. , Yin Shen , Hao Jing Qi , Zhu Qian , Mun Yong , Budde L. Elizabeth 
Published: December 2024

Background: Mosunetuzumab is a CD20xCD3 T-cell engaging bispecific antibody that is being evaluated in patients with select B-cell non-Hodgkin lymphoma (B-NHL) histologies in a Phase I/II clinical trial (NCT02500407). Mosunetuzumab is approved by the FDA and EMA for the treatment of patients with relapsed/refractory (R/R) follicular lymphoma (FL) after ≥2 prior lines of systemic therapy. A key emerging question is the optimal treatment sequence of mosunetuzumab and CD19-targeted chimeric antigen receptor (CAR) T-cell therapies, and whether CAR T-cell therapies remain clinically active post mosunetuzumab treatment. Previous data are limited but have shown that the efficacy of CAR T-cell therapies is preserved in patients with B-NHL who progressed following treatment with bispecific antibodies (Crochet et al. Blood 2022; Iacoboni et al. Blood 2023). Here, we present a US multicenter, retrospective, case series to explore the outcomes of patients with R/R B-NHL treated with CAR T-cell therapy after prior mosunetuzumab treatment.

Methods: Patients from a Phase I/II clinical trial (NCT02500407) were included in this analysis, including patients across dose-escalation cohorts. Efficacy and safety outcomes were investigated in patients with R/R B-NHL who received CAR T-cell therapy for the first time following mosunetuzumab treatment. Eligible patients were treated with CAR T-cell therapy between March 21, 2019 and June 7, 2021.

Results: At data cut-off (May 2, 2023), 26 patients with R/R B-NHL from seven institutions had received CAR T-cell therapy after mosunetuzumab treatment. Data for 11 patients from a single institution are presented here. Median age was 70 years (range: 53-81) and most patients were male (72.7%). Six patients had indolent B-NHL (all FL) and 5 patients had aggressive B-NHL (mantle cell lymphoma, n=3; diffuse large B-cell lymphoma, n=2). The median number of therapies prior to mosunetuzumab was 4 (range: 2-6). Best overall response (BOR; complete response [CR] or partial response [PR]) to mosunetuzumab by investigator assessment was 66.7% (4/6 patients; CR, n=1; PR, n=3) in patients with indolent B-NHL and 60.0% (3/5 patients; CR, n=1; PR, n=2) in those with aggressive B-NHL. The median duration of mosunetuzumab treatment was 4.4 months (range: 1.9-13.5).

Median time from mosunetuzumab initiation to CAR T-cell therapy initiation was 16.6 months (range: 2.3-30.5). Median number of therapies prior to CAR T-cell therapy was 5 (range: 2-8); mosunetuzumab was the last line of treatment before CAR T-cell therapy in 6 (54.5%) patients. Two (18.2%) patients received bendamustine within 12 months prior to administration of CAR T-cell therapy. Three (27.3%) patients received bridging therapy with radiation. All patients received CAR T-cell therapy in the inpatient setting, with 8 (72.7%) receiving it in a clinical trial. The CAR T-cell therapies received were an investigational CD19-targeted CAR T-cell therapy (n=4), axicabtagene ciloleucel (n=3), brexucabtagene autoleucel (n=2), and tisagenlecleucel (n=2).

As of July 12, 2024, in patients with indolent B-NHL, the BOR rate with CAR T-cell therapy was 100% (6/6), with 3 (50.0%) patients achieving a CR; duration of response (DOR) ranged from 3.4 to 59.3 months, with 4 responses ongoing. In patients with aggressive B-NHL, the BOR rate with CAR T-cell therapy was 80% (4/5), with all 4 patients achieving a CR; DOR ranged from 1.4 to 52.3 months.

During follow-up, in the overall cohort, 3 patients died due to disease progression, pneumonia, or sepsis (n=1 each). Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were observed in 54.5% (6/11) and 45.5% (5/11) of patients, respectively. All CRS and ICANS events were Grade (Gr) 1/2 (CRS: Gr 1, n=2; Gr 2, n=4; ICANS: Gr 1, n=1; Gr 2, n=4) and resolved by data cut-off.

Conclusions: This real-world analysis in patients with R/R B-NHL demonstrates that the clinical activity of CAR T-cell therapy is preserved following treatment with mosunetuzumab, and that the safety profile was consistent with that previously reported. These results suggest that CAR T-cell therapy is a good treatment option post mosunetuzumab for patients with R/R B-NHL; however, larger studies are needed to fully characterize the efficacy and safety of CAR T-cell therapy after mosunetuzumab. Additional patient data, including from other institutions, will be presented.