{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:46:13Z","timestamp":1760132773751,"version":"build-2065373602"},"reference-count":113,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,11,20]],"date-time":"2023-11-20T00:00:00Z","timestamp":1700438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>This review discusses immunomodulatory drug (IMiDs) sequencing and IMiD-free interval strategies for lenalidomide-refractory myeloma. IMiDs and proteasome inhibitors (PIs) improve clinical outcomes in patients with myeloma; however, refractoriness to lenalidomide, a category of IMiD, predicts poor outcomes. Next-generation IMiDs, such as pomalidomide, are effective even for lenalidomide-refractory myeloma. Therefore, an IMiD-sequencing strategy from lenalidomide to pomalidomide would be desirable. PIs are an antimyeloma therapeutic agent with another mode of action that might restore cereblon, a target of IMiDs; therefore, an IMiD-free interval via class switching from lenalidomide to PIs may be a promising alternative for lenalidomide-refractory myeloma. Additionally, the anti-CD38 monoclonal antibody is a key drug for salvage therapy in anti-CD38 monoclonal antibody-na\u00efve patients. In clinical practice, safety profiles and social convenience can play important roles in the choice of combination therapy. In the future, the selection of optimal treatments should be based on the status of the immunological environment and genetic alterations. This review aims to discuss IMiDs sequencing and IMiD-free interval strategies for lenalidomide- refractory myeloma.<\/jats:p>","DOI":"10.3390\/life13112229","type":"journal-article","created":{"date-parts":[[2023,11,20]],"date-time":"2023-11-20T01:54:12Z","timestamp":1700445252000},"page":"2229","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["IMiD-Free Interval and IMiDs Sequence: Which Strategy Is Better Suited for Lenalidomide-Refractory Myeloma?"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0300-378X","authenticated-orcid":false,"given":"Kazuhito","family":"Suzuki","sequence":"first","affiliation":[{"name":"Division of Clinical Oncology and Hematology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo 105-8461, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shingo","family":"Yano","sequence":"additional","affiliation":[{"name":"Division of Clinical Oncology and Hematology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo 105-8461, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/S0140-6736(19)32956-3","article-title":"Overall Survival with Daratumumab, Bortezomib, Melphalan, and Prednisone in Newly Diagnosed Multiple Myeloma (ALCYONE): A Randomised, Open-Label, Phase 3 Trial","volume":"395","author":"Mateos","year":"2020","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1016\/S1470-2045(21)00466-6","article-title":"Daratumumab, Lenalidomide, and Dexamethasone versus Lenalidomide and Dexamethasone Alone in Newly Diagnosed Multiple Myeloma (MAIA): Overall Survival Results from a Randomised, Open-Label, Phase 3 Trial","volume":"22","author":"Facon","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1016\/S1470-2045(21)00428-9","article-title":"Maintenance with Daratumumab or Observation Following Treatment with Bortezomib, Thalidomide, and Dexamethasone with or without Daratumumab and Autologous Stem-Cell Transplant in Patients with Newly Diagnosed Multiple Myeloma (CASSIOPEIA): An Open-Label, Randomised, Phase 3 Trial","volume":"22","author":"Moreau","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1182\/blood.2020005288","article-title":"Daratumumab, Lenalidomide, Bortezomib, and Dexamethasone for Transplant-Eligible Newly Diagnosed Multiple Myeloma: The GRIFFIN Trial","volume":"136","author":"Voorhees","year":"2020","journal-title":"Blood"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/S1470-2045(19)30152-4","article-title":"Pomalidomide, Bortezomib, and Dexamethasone for Patients with Relapsed or Refractory Multiple Myeloma Previously Treated with Lenalidomide (OPTIMISMM): A Randomised, Open-Label, Phase 3 Trial","volume":"20","author":"Richardson","year":"2019","journal-title":"Lancet Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S1470-2045(15)00464-7","article-title":"Carfilzomib and Dexamethasone versus Bortezomib and Dexamethasone for Patients with Relapsed or Refractory Multiple Myeloma (ENDEAVOR): A Randomised, Phase 3, Open-Label, Multicentre Study","volume":"17","author":"Dimopoulos","year":"2016","journal-title":"Lancet Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1056\/NEJMoa1606038","article-title":"Daratumumab, Bortezomib, and Dexamethasone for Multiple Myeloma","volume":"375","author":"Palumbo","year":"2016","journal-title":"N. 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