Introduction: Bridging treatment prior to administration of chimeric antigen receptor (CAR) T-cells in patients with relapsed/refractory multiple myeloma (RRMM) is necessary for most patients to prevent disease progression or death during the manufacturing process. Selection of bridging therapy in heavily pretreated patients with RRMM is complex. The optimal regimen includes a medication the patient is not refractory to that will minimize disease burden, reduce risk of disease progression and subsequent end organ damage, and minimize toxicities. Talquetamab is a first in class GPRC5DxCD3 bispecific antibody that offers a novel target for most patients with high rates of response in clinical trials, which offers potential as bridging therapy.

Methods: We evaluated patients who received talquetamab bridging therapy with the intent to proceed to either idecabtagene vicleucel (ide-cel) or ciltacabtagene autoleucel (cilta-cel) at Emory University Hospital between 10/1/2023 and 6/30/2025. We evaluated efficacy and safety of talquetamab as well as CRS, ICANS and GPRC5D associated toxicities. Adverse effects including CRS and neurotoxicity were evaluated utilizing the American Society for Transplantation and Cellular Therapy Consensus Grading.

Results: Between October 2023 and June 2025, 25 patients received talquetamab bridging therapy with a median follow-up of 370 days from the start of bridging therapy. The median age of the patients was 66 years (range 38-80). 24% (6 patients) had received a prior BCMA directed therapy, including 3 that had received ide-cel. Patients received a median of 4 (range 3-8) prior lines of therapy, and all patients were refractory to IMiDs, proteasome inhibitors and anti-CD38 monoclonal antibodies. Due to various factors including rapid disease progression, 52% (13) received a dose of talquetamab prior to leukapheresis. All patients were intended to receive cilta-cel.

The overall response rate for talquetamab bridging therapy was 88% (22), with 56% achieving a VGPR or better. All patients received prophylactic tocilizumab prior to the first step-up dose of talquetamab per institutional protocol. CRS occurred in 36% (9), with 7 grade 1 events and 2 grade 2 events. ICANS occurred in 16% (4), including one grade 4 event. 24 patients were evaluable for GPRC5D associated toxicities. 100% (24) reported dysgeusia, ageusia or xerostomia, 67% (16) reported rash or non-rash skin changes, and 38% (9) reported nail changes or nail loss. All patients reported resolution of these toxicities by the last follow-up. Of the 25 patients who received talquetamab bridging, 2 died prior to T-cell infusion including 1 death from HLH during step-up dosing and 1 due to disease progression on talquetamab.

23 patients received cilta-cel at a median of 87 days (range 37-266) after talquetamab initiation. 100% (23) achieved a VGPR or better by day 100 restaging after cilta-cel infusion. CRS occurred in 35% (8) including 7 grade 1 events and 1 grade 2 event. Grade 1 ICANS occurred in 4.3% (1). Disease progression occurred in 22% (5) at a median of 209 days (range 106-335) after cilta-cel infusion, and 9% (2) died after disease progression.

Conclusion: Talquetamab is a efficacious and safe bridging therapy for patients with heavily pretreated RRMM. It was associated with high rates of response, and toxicities were manageable and resolved after discontinuation of therapy. Bridging therapy did not impact response rate to cilta-cel, though longer duration of follow-up is needed to assess the durability of the responses. Bridging with talquetamab may also reduce the incidence of CRS and ICANS with cilta-cel compared to those seen in clinical trials. Longer term follow up and details regarding the CAR T-cell products will be presented at the meeting.

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2025
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