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The upfront use of immunomodulatory drug and proteasome inhibitor combinations followed by maintenance has resulted in transformative clinical benefit. Four\u2010drug regimens incorporating monoclonal antibodies are reporting unprecedented rates of complete response and MRD negativity in the absence of intensification. In the context of these advances, the added value of high\u2010dose melphalan with autologous stem\u2010cell transplant (HDM\u2010ASCT) is a key question. From a safety standpoint, HDM\u2010ASCT is associated with both acute toxicities that reduce quality of life and long\u2010term toxicities that may limit life expectancy for some patients. The present review discusses the recent advances in induction therapy, the impact of these advances on HDM\u2010ASCT, the evolving role of MRD testing and the short\u2010 and long\u2010term risks of HDM\u2010ASCT. Recognising that prospective data remains limited, we suggest that HDM\u2010ASCT not be considered mandatory for eligible newly diagnosed patients who are treated with highly efficacious regimens and achieve deep responses, but rather be held in reserve without early exposure to the clinical and genomic toxicity inherent to this approach.<\/jats:p>","DOI":"10.1111\/bjh.16764","type":"journal-article","created":{"date-parts":[[2020,6,5]],"date-time":"2020-06-05T13:14:57Z","timestamp":1591362897000},"page":"692-703","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["The role of high\u2010dose melphalan with autologous stem\u2010cell transplant in multiple myeloma: is it time for a paradigm shift?"],"prefix":"10.1111","volume":"191","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6593-0917","authenticated-orcid":false,"given":"Dickran","family":"Kazandjian","sequence":"first","affiliation":[{"name":"Multiple Myeloma Program Lymphoid Malignancies Branch Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8190-2484","authenticated-orcid":false,"given":"Clifton C.","family":"Mo","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Dana\u2010Farber Cancer Institute Jerome Lipper Multiple Myeloma Center Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6485-4839","authenticated-orcid":false,"given":"Ola","family":"Landgren","sequence":"additional","affiliation":[{"name":"Myeloma Service Department of Medicine Memorial Sloan Kettering Cancer Center New York City NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7426-8865","authenticated-orcid":false,"given":"Paul G.","family":"Richardson","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Dana\u2010Farber Cancer Institute Jerome Lipper Multiple Myeloma Center Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,6,5]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21551"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)31240-1"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2019-123465"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2018.07.016"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2017.174573"},{"key":"e_1_2_11_7_1","unstructured":"National Comprehensive Cancer Network (NCCN).Multiple Myeloma Version 2.2020. 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