Current use of bispecific antibodies to treat multiple myeloma

Targeted immunotherapy has significantly improved the outcome of patients with hematological malignancies by leverag ing the power of the immune sys tem to elim i nate tumor cells. In mul ti ple mye loma (MM), bispecifi c T - cell engagers (BsAb) targeting B - cell mat u ra tion anti gen (BCMA), G pro tein - cou pled recep tor, class C, group 5, mem ber D (GPRC5D), and Fc recep tor - like 5 (FcRL5) have already dem on strated remark able clin i cal activ ity in tri ple - class refrac tory patients. However, responses to BsAb are not uni ver sal, and resis tance often emerges while on ther apy. Mechanisms medi at ing resis tance are tumor intrin sic or immune depen dent. Reported tumor intrin sic fac tors include anti genic loss (biallelic or func tional) through dele tions or muta tions of tar get genes, increased sol u ble BCMA (for BCMA targeting BsAb), high tumor bur den, and extramedullary dis ease. Immune - medi ated resis tance are largely depen dent on T - cell fi t ness and toler ant immune envi ron ment. Understanding these mech a nisms will allow the design of opti mized BsAb ther apy and an informed approach to sequenc ing and com bin ing these mol e cules with other anti - MM agents and immune ther a pies.