PMID- 36151787 OWN - NLM STAT- MEDLINE DCOM- 20230224 LR - 20230615 IS - 2045-7634 (Electronic) IS - 2045-7634 (Linking) VI - 12 IP - 3 DP - 2023 Feb TI - Duration of frontline therapy and impact on clinical outcomes in newly diagnosed multiple myeloma patients not receiving frontline stem cell transplant. PG - 3145-3159 LID - 10.1002/cam4.5239 [doi] AB - BACKGROUND: Extended first-line therapy (1LT) has improved clinical outcomes in newly diagnosed multiple myeloma (NDMM). This retrospective study of NDMM patients evaluated the relationship between dose-attenuation of 1LT and duration of therapy (DOT) and DOT on outcomes. METHODS: Adults with NDMM not undergoing stem cell transplant (SCT) from January 1, 2012 toMarch 31, 2018 from the Integrated Oncology Network were included; 300 were randomly selected for chart review. 1LT DOT, time to next treatment (TTNT), progression-free survival (PFS), and overall survival (OS) were estimated using Kaplan-Meier analysis. Marginal structural models evaluated relationships between DOT and TTNT, PFS, and OS at 2 years accounting for confounders and survival bias from the time-dependent nature of DOT. RESULTS: Of 300 chart-reviewed patients, 93 were excluded for incomplete data or meeting exclusion criteria. Among 207 NDMM patients, median age was 74 years; 146 (70.5%) did not receive dose-attenuation during 1LT. Patients with short DOT were older, frailer, with a higher comorbidity burden, and a significantly lower proportion had an Eastern Cooperative Oncology Group PS = 0. As DOT increased, more patients underwent dose-attenuation (p < 0.0001). The median 1LT DOT was 20.9 (95% confidence interval [CI]: 13.9, 26.4) versus 4.2 months (95% CI: 3.2, 4.9) for patients receiving versus not receiving dose-attenuation, respectively (p < 0.0001). After accounting for survival bias, confounder-adjusted TTNT was prolonged with each additional month of 1LT (odds ratio [OR]: 0.76 [95% CI: 0.75, 0.78]); likelihoods of risks of disease progression (OR: 0.87 [95% CI: 0.86, 0.88]) and death at 2 years (OR: 0.72 [95% CI: 0.70, 0.74]) were reduced with each month of 1LT (p < 0.0001 for all outcomes). CONCLUSIONS: Dose-attenuated 1LT was associated with longer DOT among patients with non-SCT NDMM. Each additional month of 1LT was associated with a reduced adjusted likelihood of disease progression and death at 2 years. Dose-attenuation of 1LT can extend DOT; longer DOT may improve clinical outcomes. CI - (c) 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. FAU - Ailawadhi, Sikander AU - Ailawadhi S AUID- ORCID: 0000-0002-8377-8111 AD - Division of Hematology and Oncology, Mayo Clinic, Jacksonville, Florida, United States. FAU - Ogbonnaya, Augustina AU - Ogbonnaya A AD - Xcenda, LLC, Carrollton, Texas, United States. FAU - Murty, Sharanya AU - Murty S AD - Xcenda, LLC, Carrollton, Texas, United States. FAU - Cherepanov, Dasha AU - Cherepanov D AD - Takeda Development Center Americas, Inc (TDCA), Lexington, Massachusetts, United States. FAU - Schroader, Bridgette Kanz AU - Schroader BK AUID- ORCID: 0000-0002-5149-4464 AD - Xcenda, LLC, Carrollton, Texas, United States. FAU - Romanus, Dorothy AU - Romanus D AD - Takeda Development Center Americas, Inc (TDCA), Lexington, Massachusetts, United States. FAU - Farrelly, Eileen AU - Farrelly E AD - Xcenda, LLC, Carrollton, Texas, United States. FAU - Chari, Ajai AU - Chari A AUID- ORCID: 0000-0002-0405-7480 AD - Hematology and Oncology, Icahn School of Medicine at Mount Sinai, New York, New York, United States. LA - eng GR - P50 CA186781/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220924 PL - United States TA - Cancer Med JT - Cancer medicine JID - 101595310 RN - 69G8BD63PP (Bortezomib) SB - IM MH - Adult MH - Humans MH - Aged MH - *Multiple Myeloma/drug therapy MH - Retrospective Studies MH - Stem Cell Transplantation MH - Progression-Free Survival MH - Disease Progression MH - Antineoplastic Combined Chemotherapy Protocols/therapeutic use MH - Bortezomib/therapeutic use PMC - PMC9939178 OTO - NOTNLM OT - chemotherapy OT - clinical management OT - multiple myeloma OT - target therapy COIS- Sikander Ailawadhi reports consulting or advisory fees from Amgen, Celgene, Janssen Biotech, Sanofi, GSK, Beigene and Takeda, research funding from Cellectar (Inst), Janssen Biotech (Inst), Pharmacyclics (Inst), BMS (inst), Xencor (inst), and Phosplatin Therapeutics (Inst). Dasha Cherepanov and Dorothy Romanus are employees of Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. Augustina Ogbonnaya, Sharanya Murty, Bridgette Kanz Schroader, and Eileen Farrelly are employees of Xcenda, LLC. Ajai Chari reports grants and personal fees from Janssen, grants and personal fees from Celgene, grants and personal fees from Novartis Pharmaceuticals, grants and personal fees from Amgen, personal fees from Bristol Myers Squibb, grants from Pharmacyclics, personal fees from Karyopharm, personal fees from Sanofi, grants and personal fees from Seattle Genetics, personal fees from Oncopeptides, grants and personal fees from Millennium/Takeda, personal fees from Antengene, personal fees from GlaxoSmithKline, and personal fees from Secura Bio. EDAT- 2022/09/25 06:00 MHDA- 2023/02/25 06:00 PMCR- 2022/09/24 CRDT- 2022/09/24 03:32 PHST- 2022/08/06 00:00 [revised] PHST- 2022/04/20 00:00 [received] PHST- 2022/09/02 00:00 [accepted] PHST- 2022/09/25 06:00 [pubmed] PHST- 2023/02/25 06:00 [medline] PHST- 2022/09/24 03:32 [entrez] PHST- 2022/09/24 00:00 [pmc-release] AID - CAM45239 [pii] AID - 10.1002/cam4.5239 [doi] PST - ppublish SO - Cancer Med. 2023 Feb;12(3):3145-3159. doi: 10.1002/cam4.5239. Epub 2022 Sep 24.