Impressive Results of Trispecific Antibody in Myeloma Presented at EHA 2025 Congress

It is hard to think of other malignancies where more progress has been made over the last couple of decades than in multiple myeloma. From the chemotherapy era of the previous millennium to the modern era of targeted drugs, immunotherapies, and cellular therapy, the median survival of myeloma patients has approximately tripled. And the rich keep getting richer. For me, one of the most interesting and exciting presentations at the European Hematology Association (EHA) 2025 Congress in Milan, Italy, this June was a plenary session presentation of the results of an ongoing phase 1 study of the trispecific antibody JNJ-5322 in patients with relapsed or refractory myeloma.

It seems like only yesterday that we started using bispecific antibodies in myeloma. The FDA first approved the BCMA x CD3–targeting bispecific antibody teclistamab-cqyv (Tecvayli) in October 2022. Subsequently, the agency approved other BCMA x CD3 bispecific antibodies—elranatamab-bccm (Elrexfio) in August 2023 and, most recently, linvoseltamab-gcpt (Lynozyfic) in July. The GPRC5D x CD3–targeting bispecific antibody talquetamab-tgvs (Talvey) is also available.

Enter trispecific antibodies. JNJ-5322 is a trispecific antibody that simultaneously targets CD3, BCMA, and GPRC5D. Theoretical advantages of having 1 antibody target BCMA and GPRC5D simultaneously include increased sensitivity due to targeting of malignant plasma cells that express either BCMA or GPRC5D but not both, and increased specificity with a reduction in toxicities due to reduced binding to cells with expression of only 1 of the target antigens. In the phase 1 trial data presented at EHA, 147 patients were treated. Only 11% of patients had received a prior bispecific antibody, and 8% had received chimeric antigen receptor (CAR) T-cell therapy. The rates of cytokine release syndrome were 69% and 20% without and with prophylactic tocilizumab, respectively. The authors concluded that the overall response rate of JNJ-5322 is comparable to that of CAR T-cell therapy. These early results suggest that trispecific antibodies may offer real benefits, even over the incredible benefits already seen with the bispecific antibodies. Not many drugs in hematology and oncology achieve such high response rates, so there is cause for optimism that trispecific antibodies will improve outcomes for patients with myeloma even further.

Watch Dr Burke discuss his column in the latest installment of Chief Insights in Oncology.