{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:18:40Z","timestamp":1785403120391,"version":"3.56.0"},"reference-count":36,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001634","name":"Gateway for Cancer Research","doi-asserted-by":"publisher","award":["6703120565"],"award-info":[{"award-number":["6703120565"]}],"id":[{"id":"10.13039\/100001634","id-type":"DOI","asserted-by":"publisher"}]},{"award":["6703120565"],"award-info":[{"award-number":["6703120565"]}],"id":[{"id":"https:\/\/ror.org\/04221f920","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: High-dose melphalan 140\u2013200 mg\/m2 (HDM) with autologous stem cell transplant (ASCT) is standard first-line treatment in multiple myeloma (MM), yet standard BSA-based dosing results in wide variation in systemic exposure (AUC). We developed a pharmacokinetic (PK)-guided dosing strategy using a 100 mg\/m2 first dose, enabling real-time PK assessment and individualized adjustment for the second dose. We report final results of Phase A of our multi-center Phase 1 trial (NCT04483206, MyMel) evaluating feasibility and accuracy of this personalized approach. Methods: Patients received melphalan 100 mg\/m2 on Day \u22123, and seven PK samples were collected and shipped overnight for LC-MS\/MS analysis. Real-time AUC estimation using noncompartmental analysis (NCA) guided Day \u22121 dosing to achieve pre-specified AUC targets (13.5 or 14.5 mg \u00d7 h\/L). For comparison, post hoc Bayesian estimation using a nonlinear mixed effects (NLME) model was performed. Sparse sampling designs were evaluated using NONMEM. Results: All 20 patients successfully received PK-guided dosing, with Day \u22121 doses determined within 48 h. PK-guided dosing reduced AUC variability (CV 4.20\u20135.62%), with 19 of 20 achieving AUCs within \u00b110% of the target, compared to what would have been achieved by BSA dosing (CV 9.74\u201315.34%). NLME improved accuracy, particularly in patients with missing samples, and maintained performance using only four PK time points. Conclusions: This study demonstrates that PK-guided dosing is accurate and feasible with HDM-ASCT. NLME enhances accuracy and enables simplified sampling. Phase B will identify maximum tolerated systemic exposure of seven additional AUC cohorts using the NLME model and a four-sample design.<\/jats:p>","DOI":"10.3390\/pharmaceutics18080924","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T16:11:56Z","timestamp":1785168716000},"page":"924","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Accuracy of Real-Time PK-Guided Melphalan Dosing in Achieving Target Exposure in Myeloma Patients Undergoing Autologous Transplant"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8333-8001","authenticated-orcid":false,"given":"Kyeongmin","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Pharmacy Practice, University of Illinois Chicago, Chicago, IL 60607, USA"},{"name":"Division of Pharmaceutics and Pharmacology, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yizhen","family":"Guo","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutics and Pharmacology, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8675-8976","authenticated-orcid":false,"given":"Min","family":"Hai","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutics and Pharmacology, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kasey","family":"Hill","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Abbott","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matias Eugenio","family":"Sanchez","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, University of Illinois Chicago, Chicago, IL 60607, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chukwuemeka","family":"Uzoka","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, University of Illinois Chicago, Chicago, IL 60607, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Maria Avila","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, University of Illinois Chicago, Chicago, IL 60607, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3116-4545","authenticated-orcid":false,"given":"John G.","family":"Quigley","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, University of Illinois Chicago, Chicago, IL 60607, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadim","family":"Mahmud","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, University of Illinois Chicago, Chicago, IL 60607, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damiano","family":"Rondelli","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, University of Illinois Chicago, Chicago, IL 60607, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4268-2698","authenticated-orcid":false,"given":"Douglas W.","family":"Sborov","sequence":"additional","affiliation":[{"name":"Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald","family":"Harvey","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald J.","family":"Irby","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutics and Pharmacology, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajay K.","family":"Nooka","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhav V.","family":"Dhodapkar","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan L.","family":"Kaufman","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nisha S.","family":"Joseph","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sagar","family":"Lonial","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pritesh","family":"Patel","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, University of Illinois Chicago, Chicago, IL 60607, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1615-5280","authenticated-orcid":false,"given":"Mitch A.","family":"Phelps","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutics and Pharmacology, The Ohio State University, Columbus, OH 43210, USA"},{"name":"Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4816-1607","authenticated-orcid":false,"given":"Craig C.","family":"Hofmeister","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Sweiss","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, University of Illinois Chicago, Chicago, IL 60607, 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