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Four cycles of V\u2010IND with bortezomib\u2013cyclophosphamide\u2013dexamethasone or bortezomib\u2013lenalidomide\u2013dexamethasone are available via the Pharmaceutical Benefits Scheme prior to autologous stem cell transplantation (ASCT). Patients who demonstrate suboptimal response or who are refractory to V\u2010IND demonstrate inferior survival, representing a subgroup of MM where an unmet need persists. We evaluated an early, response\u2010adapted approach in these patients by switching to an intensive sequential therapeutic strategy incorporating daratumumab\u2013lenalidomide\u2013dexamethasone\u2010based (DRd) salvage, high\u2010dose melphalan ASCT followed by DRd consolidation and R maintenance. The overall response rate following four cycles of DRd salvage was 72% (95% credible interval: 57.9\u201382.4); prespecified, dual, Bayesian proof\u2010of\u2010concept criteria were met. Euro\u2010flow minimal residual disease (MRD) negativity was 46% in the intention\u2010to\u2010treat population and 79% in the evaluable population following 12 cycles of DRd consolidation. At the 24\u2010month follow\u2010up, median progression\u2010free survival and overall survival were not reached. DRd salvage was well tolerated with grade 3 and 4 events reported in 24% and 8% respectively. Response\u2010adapted DRd combined with ASCT achieves high rates of MRD negativity and durable disease control in this functional high\u2010risk group.<\/jats:p>","DOI":"10.1111\/bjh.19578","type":"journal-article","created":{"date-parts":[[2024,6,8]],"date-time":"2024-06-08T11:04:31Z","timestamp":1717844671000},"page":"900-914","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Response adaptive salvage treatment with daratumumab\u2013lenalidomide\u2013dexamethasone for newly diagnosed transplant\u2010eligible multiple myeloma patients failing front\u2010line bortezomib\u2010based induction therapy\u2014ALLG MM21"],"prefix":"10.1111","volume":"205","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6990-8832","authenticated-orcid":false,"given":"S.","family":"Lim","sequence":"first","affiliation":[{"name":"Alfred Health  Melbourne Victoria Australia"},{"name":"Australian Centre for Blood Diseases Monash University  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