Optimal Sequencing of Bispecific Antibodies and CAR T Cells Remains Unclear

Sequencing bispecific antibodies and CAR T-cell therapy in multiple myeloma and lymphoma was among the unresolved questions discussed at the 2026 National ICE-T Congress in Orlando, Florida, particularly for anti-BCMA approaches that target the same antigen in multiple myeloma.

Megan Melody, MD, MS, a malignant hematologist specializing in lymphoma and cellular therapy and clinical director of Cellular Therapy at Tampa General Hospital, spoke with CancerNetwork^® about why this question remains open and what data are still needed.

Transcript:

CancerNetwork: What is an unresolved question from this year’s meeting, or this meeting’s agenda, that you personally still do not feel is well answered by the current data?

Melody: In both the multiple myeloma space and the lymphoma space, we are seeing a lot of bispecific antibodies, or T-cell-engaging therapies. Some target the same targets as CAR T-cell therapy, in the case of anti-BCMA bispecific antibodies and anti-BCMA CAR T-cell therapy, and some are simply T-cell-engaging therapies. There have been studies showing that sequencing anti-BCMA therapy before CAR T-cell therapy does impact the efficacy of CAR T-cell therapy. There are also suggestions and some real-world evidence presented at last year’s American Society of Hematology [ASH] meeting from the ABC consortium that patients treated with CAR T-cell therapy before bispecific antibodies had a better response to CAR T-cell therapy.

Regardless, we need to put our best foot forward in frontline therapy, and there are some novel clinical trials emerging that use bispecific antibodies in combination with chemoimmunotherapy in the frontline setting. Bispecific antibodies are going to end up being given prior to CAR T-cell therapy in a select patient population if the data read out correctly. Knowing exactly how to sequence these therapies, what the optimal treatment gap is before apheresis, and the optimal way to sequence bispecific antibodies before CAR T-cell therapy—or vice versa—[may] improve patient outcomes. It is going to be years before we have that data because we are going to need to see it play out in the real-world setting.

Reference

Wang JS, Ellsworth BL, Melody M, et al. Outcomes for CART as 2L vs 3L vs 4L or beyond in aggressive B-cell lymphoma: real-world evidence from the ABC Consortium. Blood Adv. 2025;10(3):725-732. Doi:10.1182/bloodadvances.2025017120