Outcomes of CAR T-cell therapies after prior treatment with fixed-duration mosunetuzumab in patients with relapsed/refractory B-cell non-Hodgkin lymphoma

Abstract

Abstract Background: Mosunetuzumab (Mosun) is a CD20xCD3 bispecific antibody (BsAb) evaluated in patients (pts) with B-cell non-Hodgkin lymphoma (B-NHL) in a Phase I/II clinical trial (NCT02500407). Based on this study, intravenous (IV) Mosun is approved for the treatment of pts with relapsed/refractory (R/R) follicular lymphoma (FL) after ≥2 prior lines of systemic therapy. The optimal sequencing of available therapies and whether prior exposure to BsAbs impacts the effectiveness of subsequent CD19-targeted chimeric antigen receptor (CAR) T-cell therapies remain unclear. Limited data suggest that the efficacy of CAR T-cell therapies is preserved in pts with large B-cell lymphoma (LBCL) who received prior BsAbs (Crochet et al. Blood 2024). Here, we present a US multicenter, retrospective, case series to evaluate the outcomes of pts with R/R B-NHL treated with CAR T-cell therapy after Mosun. Methods: Pts from all dose-escalation and expansion cohorts in a Phase I/II clinical trial (NCT02500407) were included in this analysis. Efficacy and safety outcomes were investigated in pts with R/R B-NHL who received CAR T-cell therapy for the first time following Mosun treatment. Eligible pts were treated with autologous CAR T-cell therapy between December 8, 2015 and August 9, 2021. Results: At data cut-off (May 13, 2024), 48 pts with R/R B-NHL had received CAR T-cell therapy following Mosun treatment; available data from 22 pts are presented here. Median age was 67 years (range: 52–81) and 72.7% of pts were male. Thirteen pts had aggressive B-NHL (LBCL, n=6; mantle cell lymphoma [MCL], n=5; transformed FL [trFL], n=2) and 9 pts had indolent B-NHL (all FL). Pts had a median of 4 prior therapies (range: 2–7) before Mosun. Twenty-one pts received Mosun IV and 1 received a subcutaneous formulation. Investigator-assessed best overall response (BOR; complete response [CR] or partial response) to Mosun was 50.0% (4/8 pts; CR, n=0) in pts with LBCL/trFL, 60.0% (3/5 pts; CR, n=2) in pts with MCL, and 66.7% (6/9 pts; CR, n=2) in pts with FL. The median duration of Mosun treatment was 3.0 months (mo; range: 1.4–5.7), 4.8 mo (range: 1.9–7.7), and 5.1 mo (range: 1.4–13.5) in pts with LBCL/trFL, MCL, and FL, respectively. Median time from the initiation of Mosun to the administration of CAR T-cell therapy was 11.8 mo (range: 2.3–30.5). Median number of therapies prior to CAR T-cell therapy was 5 (range: 2–11); Mosun was the last line of treatment before CAR T-cell therapy in 12 (54.5%) pts. Two (9.1%) pts received bendamustine within 12 mo prior to leukapheresis and 3 (13.6%) pts received bridging therapy (radiation [RT], n=2; RT and venetoclax, n=1). The CAR T-cell therapies received were axicabtagene ciloleucel (n=12), brexucabtagene autoleucel (n=3), tisagenlecleucel (n=2), lisocabtagene maraleucel (n=1), and an investigational CD19-targeted CAR T-cell therapy (n=4). Twelve (54.5%) pts received CAR T-cell therapy in a clinical trial. At the site-specific data cut-off (City of Hope: July 12, 2024; MD Anderson: February 11, 2025; Fred Hutchinson: February 26, 2025; and Washington University: May 30, 2025), in pts with LBCL/trFL the BOR rate with CAR T-cell therapy was 87.5% (7/8; CR, n=6); duration of response (DOR) ranged from 1.4 to 52.3 mo, with 2 responses ongoing. In pts with MCL, the BOR rate was 40.0% (2/5; CR, n=2); DOR ranged from 22.8 to 36.3 mo, with 1 response ongoing. In pts with FL, the BOR rate was 100% (9/9; CR, n=6); DOR ranged from 3.4 to 61.1 mo, with 5 responses ongoing. During follow-up, 9 pts in the overall cohort died: 5 due to lymphoma and 1 each due to acute renal failure, infection, pneumonia, and sepsis. Cytokine release syndrome (CRS) after CAR T-cell therapy was observed in 68.2% (15/22) of pts, all cases were low grade (Gr; Gr 1, n=8; Gr 2, n=7). Immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in 36.4% (8/22) of pts (Gr 1, n=2; Gr 2, n=4; Gr 3, n=1; Gr 4, n=1). By data cut-off, CRS was resolved in all pts and ICANS in 7/8 pts. Conclusions: This real-world multicenter analysis suggests that prior Mosun treatment does not impair the efficacy of subsequent CAR T-cell therapy in pts with R/R B-NHL, with the safety profile consistent with previously published data. These results support CAR T-cell therapy as a viable treatment option following BsAb treatment. Further studies are needed to fully characterize and validate the efficacy and safety of CAR T-cell therapy after BsAbs such as Mosun.