Hultcrantz M, Hassoun H, Korde N, Maclachlan K, Mailankody S, Patel D, Shah U, Tan CR, Chung DJ, Lahoud O, Landau H, Scordo M, Shah GL, Giralt S, Pianko MJ, Burge M, Barnett K, Salcedo M, Caple J, Tran L, Blaslov J, Shekarkhand T, Hamid S, Nemikovski D, Derkach A, Arisa O, Peer CJ, Figg WD, Usmani SZ, Landgren O, and Lesokhin AM
Lenalidomide maintenance is associated with a significantly improved progression-free in patients with newly diagnosed multiple myeloma. Maintenance with lenalidomide is generally well tolerated; however, lenalidomide associated diarrhea is a common side effect and bile acid malabsorption has been suggested as an underlying mechanism. We conducted a single arm phase 2 trial of colesevelam, a bile acid binder, for lenalidomide-associated diarrhea in multiple myeloma. Patients were treated with colesevelam daily starting at 1250 mg (2 tablets 625 mg) for 12 weeks. The trial included 25 patients, 1 patient with grade 3 diarrhea, 14 with grade 2, and 10 with grade 1 diarrhea. All patients were on treatment with single agent lenalidomide maintenance and no patient progressed during the trial. Colesevelam treatment was highly effective for treatment of lenalidomide-associated diarrhea; 22 (88%) of the 25 patients responded where 17 patients (68%) had complete resolution of diarrhea, and 5 patients (20%) had improvement by 1 grade of diarrhea. The responses to colesevelam were seen within the first two weeks of treatment. These findings support the conclusion that lenalidomide-associated diarrhea is driven by bile acid malabsorption. Five patients reported mild gastrointestinal side effects including constipation. Importantly, the pharmacokinetics of lenalidomide were not affected by concomitant colesevelam treatment. The stool microbiome composition was not significantly different before and after colesevelam treatment. Patients reported improved diarrhea, fewer gastrointestinal symptoms, and less interference with their daily life after starting colesevelam. In summary, colesevelam was safe and highly effective for treatment of lenalidomide-associated diarrhea in multiple myeloma and does not reduce the clinical effect of lenalidomide., Competing Interests: Conflict of interest disclosure MH reports research funding from Daiichi Sankyo, Cosette Pharmaceuticals, GlaxoSmithKline, Abbvie, Beigene; has received honoraria for consultancy/participated in advisory boards for Curio Science LLC, Projects in Knowledge, Intellisphere LLC, Bristol Myers Squibb, Janssen, and GlaxoSmithKline. HH reports grants from Celgene, Takeda, and Janssen; NK reports research funding through Amgen and participates in advisory board with Medimmune. KM reports grant support from ASH, MMRF, and IMS. SM reports research funding from Allogene Therapeutics, Juno/Bristol Myers Squibb, Takeda Oncology, and Janssen Oncology; personal fees from Plexus communication, and Physician Education Resource. UAS reports personal fees from Physicians Educations Resources; grants and other from Celgene/Bristol Myers Squibb; other from Janssen; and grants from Parker Institute for Cancer Immunotherapy and HealthTree Foundation. CRT reports research funding from Janssen and personal fees from Physician Educations Resource; DJC receives research funding from Genentech; HL has served as a paid consultant for Takeda, Genzyme, Janssen, Karyopharm, Pfizer, Celgene, Caelum Biosciences, and has received research support from Takeda. MS served as a paid consultant for McKinsey & Company, Angiocrine Bioscience, Inc., and Omeros Corporation; received research funding from Angiocrine Bioscience, Inc., Omeros Corporation, and Amgen, Inc.; served on ad hoc advisory boards for Kite – A Gilead Company; and received honoraria from i3Health, Medscape, and CancerNetwork for CME-related activity. GLS reports research funding from Janssen, Amgen, BMS, Beyond Spring, and serves on the Data Safety Monitoring Board for ArcellX. SG reports personal fees and advisory role (scientific advisory board) from Actinium, Celgene, Bristol Myers Squibb, Sanofi, Amgen, Pfizer, GlaxoSmithKline, JAZZ, Janssen, Omeros, Takeda, and Kite. MP Research Funding: Celgene/BMS, Abbvie, Nektar, Sanofi, Pfizer, Regeneron Honoraria/Consultancy: Janssen, Sanofi, Oncopeptides, Karyopharm, GSK, Pfizer; OBL reports serving on Advisory Board for MorphoSys; SZU reports grants and personal fees from AbbVie, Amgen, BMS, Celgene, GSK, Janssen, Merck, MundiPharma, Oncopeptides, Pharmacyclics, Sanofi, Seattle Genetics, SkylineDX, and Takeda. OL acknowledges funding from: NCI/NIH, FDA, LLS, Rising Tide Foundation, MMRF, IMF, Paula and Rodger Riney Foundation, Perelman Family Foundation, Amgen, Celgene, Janssen, Takeda, Glenmark, Seattle Genetics, Karyopharm; has received honoraria for scientific talks/participated in advisory boards for Adaptive, Amgen, Binding Site, BMS, Celgene, Cellectis, Glenmark, Janssen, Juno, Pfizer; and served on Independent Data Monitoring Committees (IDMC) for international randomized trials by: Takeda, Merck, Janssen, Theradex. AML reports grants from Novartis, during the conduct of the study; grants from Bristol Myers Squibb; personal fees from Trillium Therapeutics; grants, personal fees and non-financial support from Pfizer; and grants and personal fees from Janssen. AML also has a patent US20150037346A1 with royalties paid; The remaining authors have no competing interest to disclose.