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Treatment selection and sequencing become increasingly complex with the broad range of therapeutic options. In this review, the European Myeloma Network provides recommendations on how to best incorporate these novel therapies into the present treatment landscape using current evidence. The optimal treatment sequence depends on various patient\u2010 and tumor\u2010related features, but also reimbursement and availability issues. In addition, mechanisms underlying relapse (e.g., antigen loss, reduced T\u2010cell fitness, or outgrowth of T\u2010cell resistant clones) dictate the efficacy of sequential BCMA\u2010 or GPRC5D\u2010directed immunotherapy. BCMA\u2010targeting BsAbs and ADCs should preferably be avoided prior to CAR T\u2010cell therapy, as some studies have shown that these agents negatively influence clinical outcomes after CAR T\u2010cell therapy. Therefore, we recommend the selection of CAR T\u2010cell therapy first, and BsAbs and\/or belamaf later in the disease course, if patients are eligible for CAR T\u2010cell therapy and in case CAR T\u2010cell therapy is available within a short time frame. However, bridging therapy with GPRC5D\u2010directed BsAbs (initiation after apheresis) can be considered to significantly reduce tumor burden, because this was shown to improve the efficacy of consecutive BCMA\u2010directed CAR T\u2010cell therapy. Sequential treatment with agents targeting the same antigen, but with different modes of action, is feasible, but several studies have demonstrated that target switch is a more effective strategy. In addition, there is increasing evidence indicating that the efficacy of sequential use of BsAbs can be improved by creating a BsAb\u2010free interval.<\/jats:p>","DOI":"10.1002\/hem3.70260","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T14:25:22Z","timestamp":1764080722000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Sequencing BCMA\u2010 and GPRC5D\u2010targeting immunotherapies in multiple myeloma: Practical guidance from the European Myeloma Network"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7445-2603","authenticated-orcid":false,"given":"Niels W. C. 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