Immunotherapy with Antibodies in Multiple Myeloma: Monoclonals, Bispecifics, and Immunoconjugates

Abstract

In the 2010s, immunotherapy revolutionized the treatment landscape of multiple myeloma. CD38-targeting antibodies were initially applied as monotherapy in end-stage patients, but are now also approved by EMA/FDA in combination with standards-of-care in newly diagnosed disease or in patients with early relapse. The approved SLAMF7-targeting antibody can also be successfully combined with lenalidomide or pomalidomide in relapsed/refractory myeloma. Although this has resulted in improved clinical outcomes, there remains a high unmet need in patients who become refractory to immunomodulatory drugs, proteasome inhibitors and CD38-targeting antibodies. Several new antibody formats, such as antibody–drug conjugates (e.g., belantamab mafodotin, which was approved in 2020 and targets BCMA) and T cell redirecting bispecific antibodies (e.g., teclistamab, talquetamab, cevostamab, AMG-420, and CC-93269) are active in these triple-class refractory patients. Based on their promising efficacy, it is expected that these new antibody formats will also be combined with other agents in earlier disease settings.