Recent advancements in the treatment of multiple myeloma have emerged with two promising trispecific antibodies displaying remarkable early clinical results. These innovative therapies aim to address significant unmet needs in the management of relapsed and refractory multiple myeloma (R/R MM), particularly for patients with ultrahigh-risk disease and those deemed frail.
The first candidate, a trispecific antibody targeting both the B-cell maturation antigen (BCMA) and GPRC5D, achieved a striking 100% overall response rate in BCMA-naive patients at the recommended phase 2 dosing. Most participants experienced deep responses, indicating the potential for effective treatment options. The second candidate, developed by Ichnos Sciences, targets BCMA and CD38 and has also demonstrated promising preliminary data.
Addressing Antigen Escape Risks and Frontline Strategies
These trispecific agents tackle the theoretical risk of antigen escape by simultaneously targeting multiple myeloma antigens within a single therapeutic construct. This approach may significantly enhance treatment efficacy and patient outcomes. Notably, frontline combination strategies are also under active development, particularly for transplant-ineligible patients. Data from the MAGNETISMM-6 trial, presented at the EHA 2025 congress, highlights the potential of bispecific antibodies in earlier treatment lines.
Innovative constructs featuring attenuated CD3 binding are being developed to reduce the incidence of cytokine release syndrome. This could potentially lead to improved safety profiles, making these treatments more suitable for older or frail patients who often struggle with current immunomodulatory drug-based regimens.
Meeting Critical Unmet Needs in Multiple Myeloma Care
Despite the advancements in therapy, two critical unmet needs remain in multiple myeloma care: addressing the needs of ultrahigh-risk disease patients and developing strategies for truly frail individuals. Patients classified as ultrahigh-risk, particularly those with extramedullary disease, require innovative combination approaches that incorporate the most effective immunotherapies alongside emerging agents like cellular modulators.
Even with improvements seen through combination bispecific therapy, the progression-free survival rates for these patients remain suboptimal when compared to standard-risk individuals. Additionally, frail patients—who often do not qualify for clinical trials—require better-defined treatment strategies. There is a pressing need for potentially novel therapeutic approaches that cater specifically to their unique needs and limitations.
The ongoing evolution in the development of trispecific antibodies and other targeted therapies offers hope to those affected by multiple myeloma, particularly for populations that have historically faced significant treatment challenges. As research progresses, these innovative therapies could reshape the landscape of care for countless patients around the world.