Bispecific Antibodies and CAR T Redefine Early-Line Treatment in Multiple Myeloma
Key Points
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Early data from the 2025 ASH Annual Meeting (ASH 2025) suggest that bispecific antibodies and T-cell engagers may move into frontline and early-relapse settings in multiple myeloma, with high response rates and manageable toxicity.
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Improved management strategies have reduced the severity of cytokine release syndrome (CRS), which supports broader use of these agents in community practice.
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Chimeric antigen receptor (CAR) T-cell therapy remains an important early option for eligible patients.
At ASH 2025, Hamza Hashmi, MD, of Memorial Sloan Kettering Cancer Center, sat down with Robert Orlowski, MD, PhD, of MD Anderson Cancer Center, to discuss the latest in the multiple myeloma treatment landscape. Emerging data presented at the conference highlight a shift toward earlier use of bispecific antibodies and T-cell engagers, prompting discussion about how these agents may be integrated into frontline and early-relapse settings for both academic and community practices.
Results from the phase 1 LINKER-MM4 trial evaluating linvoseltamab in newly diagnosed multiple myeloma showed compelling efficacy, with an overall response rate of 86% and 43% of patients achieving a complete response. Those responses were expected to deepen with continued therapy, Dr. Orlowski said. He also expressed excitement about the use of daratumumab plus teclistamab in patients who are transplant-ineligible and frail, where significant progression-free survival and overall survival outcomes were seen, with dropping CRS rates.
While CRS rates are becoming more manageable, infection risk remains a concern. In LINKER-MM4, grade 3 infections were observed in approximately one-third of patients, which makes close monitoring important, he explained.
When considering bispecific antibodies versus CAR T-cell therapy at first relapse, Dr. Orlowski emphasized that CAR T remains a preferred option for eligible patients due to higher response rates, deeper remissions, and longer treatment-free intervals. Durable plateaus observed in the CARTITUDE trials suggest the possibility of long-term disease control or cure for some patients. However, bispecific antibodies are an effective and practical alternative for patients who cannot access CAR T or require immediate therapy.