PMID- 38318126 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240207 IS - 2589-5370 (Electronic) IS - 2589-5370 (Linking) VI - 68 DP - 2024 Feb TI - Ixazomib-based frontline therapy followed by ixazomib maintenance in frail elderly newly diagnosed with multiple myeloma: a prospective multicenter study. PG - 102431 LID - 10.1016/j.eclinm.2024.102431 [doi] LID - 102431 AB - BACKGROUND: Frail elderly patients with newly diagnosed multiple myeloma (NDMM) have inferior survival and less benefit from high-dose therapies. This prospective study aimed to investigate the efficacy, safety, and quality of life (QoL) of induction treatment of ixazomib/lenalidomide/dexamethasone (IRd) and ixazomib/pegylated liposomal doxorubicin/dexamethasone (IDd) followed by ixazomib/dexamethasone (Id) maintenance therapy in frail, elderly patients with NDMM. METHODS: From July 2019 to December 2021, this non-randomized concurrent controlled clinical study enrolled 120 NDMM patients aged >/=65 years with frailty defined by the International Myeloma Working Group (IMWG) frailty score or Mayo geriatric scoring system. The enrolled patients received 6-8 cycles of IRd or IDd followed by Id maintenance therapy for a minimum of 2 years at the discretion of physicians based on patient's clinical characteristics (chiCTR1900024917). FINDINGS: The median age was 71 years and 55% of the patients were males. The overall response rate (ORR) was 82% and 77%, complete response (CR) rate was 25% and 12% for IRd and IDd groups, respectively. The difference in ORR of the Idd group minus the IRd group was -5.36% (95% CI: -18.9% to 8.19%), indicating that the ORR of the IDd group was neither inferior nor non-inferior to the IRd group. After a median follow-up of 34.3 months, the median progression-free survival (PFS) was 21.6 and 13.9 months, OS was not reached and 29.2 months in IRd and IDd groups, respectively. 28 and 33 patients discontinued induction therapy, 20 and 19 discontinued maintenance therapy in IRd and IDd groups, respectively. Cumulative Grade 3 or higher hematological adverse events (AEs) occurred in 10 of the 60 patients (17%) and non-hematological AEs occurred in 15 of the 60 patients (25%) in the IRd group, while 13 of the 60 patients (22%) and 21 of the 60 patients (35%) in the IDd group. Patients were observed with clinically significant improvement in QoL when compared with that at baseline in both IRd and IDd groups by evaluation per cycle (P < 0.0001). INTERPRETATION: The results demonstrated that compared with IRd regimen, IDd regimen showed no significant advantage, but the survival of the IDd group was shorter than that of the IRd group, indicating an all-oral outpatient triplet regimen with IRd, which has low toxicity and has improved QoL, could be the viable first-line treatment option for frail NDMM patients. FUNDING: The Young Elite Scientist sponsorship program by bast of Beijing Association for Science and Technology (No. BYESS2023116) and Beijing Medical Award Foundation (No. YXJL-2018-0539-0073). CI - (c) 2024 The Authors. FAU - Bao, Li AU - Bao L AD - Department of Hematology, Beijing Jishuitan Hospital, Capital Medical University, Beijing, 100035, China. FAU - Wang, Yu-Tong AU - Wang YT AD - Department of Hematology, Beijing Jishuitan Hospital, Capital Medical University, Beijing, 100035, China. FAU - Liu, Peng AU - Liu P AD - Department of Hematology, Zhongshan Hospital, Fudan University, Shanghai, China. FAU - Lu, Min-Qiu AU - Lu MQ AD - Department of Hematology, Beijing Jishuitan Hospital, Capital Medical University, Beijing, 100035, China. FAU - Zhuang, Jun-Ling AU - Zhuang JL AD - Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China. FAU - Zhang, Mei AU - Zhang M AD - Department of Hematology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi, China. FAU - Xia, Zhong-Jun AU - Xia ZJ AD - Department of Hematologic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China. FAU - Li, Zhen-Ling AU - Li ZL AD - Department of Hematology, China-Japan Friendship Hospital, Beijing, China. FAU - Yang, Ying AU - Yang Y AD - Department of Hematology, Shengjing Hospital of China Medical University, Shenyang, China. FAU - Yan, Zhen-Yu AU - Yan ZY AD - Department of Hematology, Affiliated Hospital of North China University of Science and Technology, Tangshan, China. FAU - Jing, Hong-Mei AU - Jing HM AD - Department of Hematology, Third Hospital of Peking University, Beijing, China. FAU - Dong, Fei AU - Dong F AD - Department of Hematology, Third Hospital of Peking University, Beijing, China. FAU - Chen, Wen-Ming AU - Chen WM AD - Department of Hematology, Beijing Chao Yang Hospital, Capital Medical University, Beijing, China. FAU - Wu, Yin AU - Wu Y AD - Department of Hematology, Beijing Chao Yang Hospital, Capital Medical University, Beijing, China. FAU - Zhou, He-Bing AU - Zhou HB AD - Department of Hematology, Beijing Luhe Hospital, Capital Medical University, Beijing, China. FAU - Fu, Rong AU - Fu R AD - Department of Hematology, Tianjin Medical University General Hospital, Tianjin, China. FAU - Gong, Yu-Ping AU - Gong YP AD - Department of Hematology, West China Hospital, Sichuan University, Chengdu, China. FAU - Huang, Wen-Rong AU - Huang WR AD - Department of Hematology, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, China. FAU - Zhang, Yong-Qing AU - Zhang YQ AD - Department of Hematology, The Eighth Medical Center of Chinese PLA General Hospital, Beijing, China. LA - eng PT - Journal Article DEP - 20240125 PL - England TA - EClinicalMedicine JT - EClinicalMedicine JID - 101733727 PMC - PMC10839574 OTO - NOTNLM OT - All oral regimen OT - Elderly OT - Frail OT - Multiple myeloma OT - Quality of life COIS- The authors have no conflict of interest. EDAT- 2024/02/06 06:43 MHDA- 2024/02/06 06:44 PMCR- 2024/01/25 CRDT- 2024/02/06 03:52 PHST- 2023/09/13 00:00 [received] PHST- 2023/12/23 00:00 [revised] PHST- 2024/01/09 00:00 [accepted] PHST- 2024/02/06 06:44 [medline] PHST- 2024/02/06 06:43 [pubmed] PHST- 2024/02/06 03:52 [entrez] PHST- 2024/01/25 00:00 [pmc-release] AID - S2589-5370(24)00010-5 [pii] AID - 102431 [pii] AID - 10.1016/j.eclinm.2024.102431 [doi] PST - epublish SO - EClinicalMedicine. 2024 Jan 25;68:102431. doi: 10.1016/j.eclinm.2024.102431. eCollection 2024 Feb.