Exploring the Data From LINKER-MM

EP: 1.Setting the Stage and New Milestones in Talquetamab Data

EP: 2.Diving Deeper: Long-Term Safety With Talquetamab

EP: 3.Prophylactic Tocilizumab and Sequencing Strategies in the Bispecific Era

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EP: 4.Exploring the Data From LINKER-MM

Recent clinical trials have explored combining a B-cell maturation antigen (BCMA)–targeting bispecific antibody, linvoseltamab, with proteasome inhibitors like carfilzomib and bortezomib in relapsed/refractory multiple myeloma. Linvoseltamab as a single agent has demonstrated promising activity with around a 70% response rate, but there is room to improve efficacy. Combining it with proteasome inhibitors aims to enhance antimyeloma activity while managing toxicity. Early-phase studies involving small patient groups showed encouraging overall response rates of 91% with carfilzomib and 79% with bortezomib, suggesting additive benefits in heavily pretreated patients.

The rationale for combining proteasome inhibitors with BCMA bispecific antibodies lies in their complementary mechanisms and tolerability. Unlike combinations with immunomodulatory drugs such as lenalidomide or pomalidomide, which can cause significant cytopenias, proteasome inhibitors tend to have a more manageable safety profile. These trials reported that the addition of carfilzomib or bortezomib did not substantially increase cytopenias or infection rates beyond what is expected from linvoseltamab alone. Grade 3 and 4 infections remained common but were comparable to single-agent treatment, indicating that the combination’s toxicity is manageable.

While these initial results are promising, longer follow-up is needed to assess durability of response and progression-free survival. The median duration of response has not yet been reached, highlighting the need for ongoing data maturation. These early findings support the potential of proteasome inhibitor combinations to improve outcomes without substantially increasing adverse events. Future larger studies will help define the optimal use of these combinations and whether they should become a standard part of treatment sequencing for patients with relapsed or refractory multiple myeloma.