CAR T-Cell Therapy Tops Bispecific Antibodies in Relapsed MCL

Chimeric antigen receptor (CAR) T-cell therapy produced complete responses more often than bispecific antibodies in heavily pretreated patients with relapsed or refractory mantle cell lymphoma (MCL), according to a systematic review and meta-analysis published in Frontiers in Oncology.¹

No Head-to-Head Trial Has Compared the 2 Cell-Engaging Approaches

Over the past several years, the FDA has approved multiple cell-engaging therapies for patients with MCL whose disease progressed after a Bruton tyrosine kinase inhibitor (BTKi), including the CD19-directed CAR T-cell therapy brexucabtagene autoleucel (Tecartus; Kite Pharma), which received traditional FDA approval for this indication, including in BTKi-naive patients, after a confirmatory analysis of the ZUMA-2 trial. CD20×CD3 bispecific antibodies such as mosunetuzumab and glofitamab have also moved into this space, but no randomized trial has directly compared the 2 drug classes, and the researchers noted that such a trial would be difficult to run given how heavily pretreated this population is.² To fill that gap, the researchers of the present analysis searched PubMed, Embase, and the Cochrane Library through October 2024 and pooled data from 5 studies, 2 evaluating bispecific antibodies and 3 evaluating CAR T-cell therapy, in patients with MCL who had relapsed or become refractory after at least 2 prior lines of therapy, most of whom had already received a BTKi.¹

The analysis followed PRISMA 2020 guidelines and was registered in PROSPERO. It pooled data from 237 patients across the 5 studies: 2 evaluating the CD20×CD3 bispecific antibodies mosunetuzumab and glofitamab, and 3 evaluating CAR T-cell products, including brexucabtagene autoleucel and lisocabtagene maraleucel (Breyanzi; Bristol Myers Squibb). Median patient age across the studies ranged from 65 to 68.5 years, and most patients had received at least 1 prior BTKi.

Nearly all included studies were single-arm trials rather than randomized comparisons, and outcomes were pooled using random-effects models. The researchers tested whether results differed by baseline risk score, the tumor proliferation marker Ki-67, TP53 mutation status, study size, or patient age, and found no significant interaction for any of these factors.

CAR T-Cell Therapy Produced More Complete Responses

Pooled complete response (CR) rates were 70% with CAR T-cell therapy vs 63% with bispecific antibodies (P < .05), with an overall pooled CR rate of 68% (95% CI, 62%-74%) across all 5 studies. Pooled overall response rates were 88% with CAR T-cell therapy and 75% with bispecific antibodies.

Rates of grade 3 or higher cytokine release syndrome (CRS) were low and similar between the 2 approaches, at 6% for bispecific antibodies and CAR T-cell therapy (P > .05). Grade 3 or higher neurotoxicity occurred in 21% of patients who received CAR T-cell therapy; comparable data for bispecific antibodies could not be pooled because of incomplete reporting.

“CAR T-cell therapy demonstrated higher CR rates versus bispecific antibodies,” the researchers wrote. They cautioned, however, that “randomized trials are needed to confirm these findings.”

Small, Indirect Comparison Limits How Findings Should Be Used

The researchers cautioned that their analysis compared outcomes across separate single-arm studies rather than within a randomized trial, so differences between regimens could reflect differences in patient populations rather than the treatments themselves. Without access to individual patient data, they could not adjust for age, performance status, or comorbidities across studies.

Pooled survival data were also unavailable: progression-free survival and overall survival were missing or inadequately reported in several of the included studies, so the analysis could not compare how long responses lasted between the 2 approaches. The researchers characterized their findings as hypothesis-generating rather than definitive, a caution that matters given how small and heterogeneous the underlying studies were.

For clinicians choosing among an expanding menu of cell-engaging therapies in relapsed or refractory MCL, the findings offer an early signal that CAR T-cell therapy may produce deeper responses than bispecific antibodies, without yet showing whether those responses last longer or whether the safety trade-offs favor one approach for a particular patient. For payers, the absence of durability data means site-of-care and sequencing decisions for this growing drug class will likely remain reliant on individual trial data until a prospective, head-to-head comparison is available.

References

1. Li M, Qiu L, Chen D, et al. CAR T-cell vs bispecific antibodies in relapsed/refractory mantle cell lymphoma: a systematic review and meta-analysis. Front Oncol. 2026;16:1860307. doi:10.3389/fonc.2026.1860307
2. The ASCO Post Staff. FDA grants traditional approval to brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma. The ASCO Post. April 3, 2026. Accessed October 12, 2026. https://ascopost.com/news/april-2026/fda-grants-traditional-approval-to-brexucabtagene-autoleucel-for-relapsed-or-refractory-mantle-cell-lymphoma/