PMID- 32253827 OWN - NLM STAT- MEDLINE DCOM- 20210513 LR - 20220114 IS - 2045-7634 (Electronic) IS - 2045-7634 (Linking) VI - 9 IP - 11 DP - 2020 Jun TI - Optimal treatment strategy with nilotinib for patients with newly diagnosed chronic-phase chronic myeloid leukemia based on early achievement of deep molecular response (MR(4.5) ): The phase 2, multicenter N-Road study. PG - 3742-3751 LID - 10.1002/cam4.3034 [doi] AB - For patients who have chronic myeloid leukemia (CML), one of the primary treatment options is administration of nilotinib 300 mg twice daily (BID). In previous studies which compared outcomes associated with nilotinib or imatinib treatment, nilotinib achieved a higher rate of deep molecular response (MR). We conducted a phase II, open-label, multicenter study to investigate an intrapatient nilotinib dose-escalation strategy for patients with newly diagnosed chronic-phase (CP) CML based on early MR(4.5) achievement. The primary study endpoint was achievement of MR(4.5) by 24 months following the initiation of nilotinib 300 mg BID. Fifty-three patients were enrolled, 51 received nilotinib, and 37 completed the treatment. An increase in the nilotinib dose (to 400 mg BID) was allowed when patients satisfied our criteria for no optimal response at any time point. The median (range) dose intensity was 600 (207-736) mg/day. Of 46 evaluable patients, 18 achieved an optimal response and 28 did not. Of the latter, nine patients underwent dose escalation to 400 mg BID, and none achieved MR(4.5) . The remaining 19 patients could not undergo dose escalation, 12 (63%) because of adverse events (AEs), and 7 (37%) for non-AE related reasons. Four of these patients achieved MR(4.5) . The MR(4.5) rate by 24 months was 45.7%. The progression-free, overall and event-free survival were each 97.6%. No new safety concerns were observed. Our findings support the use of continuous nilotinib at a dose of 300 mg BID for newly diagnosed patients with CML-CP. CI - (c) 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. FAU - Nishiwaki, Kaichi AU - Nishiwaki K AUID- ORCID: 0000-0003-2188-1241 AD - Division of Oncology and Hematology, Jikei University Kashiwa Hospital, Kashiwa, Japan. FAU - Sugimoto, Kei-Ji AU - Sugimoto KJ AD - Division of Hematology, Juntendo University Urayasu Hospital, Chiba, Japan. FAU - Tamaki, Shigehisa AU - Tamaki S AD - Department of Hematology/Infectious Disease, Ise Red Cross Hospital, Ise, Japan. FAU - Hisatake, Junichi AU - Hisatake J AD - Department of Hematology, Omori Red Cross Hospital, Tokyo, Japan. FAU - Yokoyama, Hisayuki AU - Yokoyama H AD - Department of Hematology, National Hospital Organization, Sendai Medical Center, Sendai, Japan. FAU - Igarashi, Tadahiko AU - Igarashi T AD - Division of Hematology and Oncology, Gunma Cancer Center, Ohta, Japan. FAU - Shinagawa, Atsushi AU - Shinagawa A AD - Department of Internal Medicine, Hitachi General Hospital, Ibaraki, Japan. FAU - Sugawara, Takeaki AU - Sugawara T AD - Division of Hematology-Oncology, Chiba Cancer Center, Chiba, Japan. FAU - Hara, Satoru AU - Hara S AD - Department of Hematology, Chiba Rosai Hospital, Chiba, Japan. FAU - Fujikawa, Kazuhisa AU - Fujikawa K AD - Department of Hematology, Chibaken Saiseikai Narashino Hospital, Narashino, Japan. FAU - Shimizu, Seiichi AU - Shimizu S AD - Department of Hematology, Tsuchiura Kyodo General Hospital, Tsuchiura, Japan. FAU - Yujiri, Toshiaki AU - Yujiri T AD - Third Department of Internal Medicine, Yamaguchi University, Yamaguchi, Japan. FAU - Tojo, Arinobu AU - Tojo A AD - Division of Molecular Therapy, Institute of Medical Science, Tokyo University, Tokyo, Japan. FAU - Wakita, Hisashi AU - Wakita H AD - Division of Hematology and Oncology, Japanese Red Cross Society, Narita Red Cross Hospital, Narita, Japan. LA - eng SI - UMIN-CTR/UMIN000008565 PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20200406 PL - United States TA - Cancer Med JT - Cancer medicine JID - 101595310 RN - 0 (Pyrimidines) RN - F41401512X (nilotinib) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Female MH - Follow-Up Studies MH - Humans MH - Leukemia, Myeloid, Chronic-Phase/*drug therapy/pathology MH - Male MH - Middle Aged MH - Non-Randomized Controlled Trials as Topic MH - Prognosis MH - Pyrimidines/*standards/*therapeutic use MH - Survival Rate MH - Young Adult PMC - PMC7286457 OTO - NOTNLM OT - chronic myeloid leukemia OT - early deep molecular response OT - nilotinib COIS- KN received a grant for this work from Novartis Pharma KK; and reports grants from Zenyaku Kogyo Company, Ltd., Asahi Kasei Pharma, and Taiho Pharmaceutical Co., Ltd., grants and personal fees from Chugai Pharmaceutical, Kyowa Hakko Kirin Co., Ltd., Nippon Shinyaku Co., Ltd., Mochida Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Sumitomo Dainippon Pharma Co., Ltd., and personal fees from Pfizer, Otsuka Pharmaceutical Co., Ltd., Janssen Pharmaceutical KK, Eisai Co., Ltd., and Celgene KK, outside the submitted work. HY reports grants from Celgene KK and Astellas Pharma Inc, outside the submitted work. AT reports personal fees from Sysmex, Otsuka Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Bristol-Myers Squib, and Takeda Pharmaceutical Co., Ltd., and grants and personal fees from Daiichi Sankyo, Pfizer, and Chugai Pharmaceutical, outside the submitted work. KS, ST, JH, TI, AS, TS, SH, KF, SS, TY, and HW have nothing to disclose. EDAT- 2020/04/08 06:00 MHDA- 2021/05/14 06:00 PMCR- 2020/04/06 CRDT- 2020/04/08 06:00 PHST- 2019/08/21 00:00 [received] PHST- 2020/03/04 00:00 [revised] PHST- 2020/03/15 00:00 [accepted] PHST- 2020/04/08 06:00 [pubmed] PHST- 2021/05/14 06:00 [medline] PHST- 2020/04/08 06:00 [entrez] PHST- 2020/04/06 00:00 [pmc-release] AID - CAM43034 [pii] AID - 10.1002/cam4.3034 [doi] PST - ppublish SO - Cancer Med. 2020 Jun;9(11):3742-3751. doi: 10.1002/cam4.3034. Epub 2020 Apr 6.