Blood. 2022;140(25):2663-2671.
Long-term outcomes in patients with relapsed or refractory hairy cell leukemia treated with vemurafenib monotherapy.
제1저자 Shivani Handa, 이정옥 · 교신저자 Jae H Park
소속 (13)
- Division of Hematology-Oncology, Icahn School of Medicine at Mount Sinai, New York, NY.
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
- Department of Biostatistics and Epidemiology, Memorial Sloan-Kettering Cancer Center, New York, NY.
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
- Division of Hematology and Oncology, Scripps Clinic, La Jolla, CA.
- Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL.
- Comprehensive Cancer Center, Ohio State University, Columbus, OH.
- Cancer Institute at Zucker School of Medicine Hofstra-Northwell, New Hyde Park, NY.
- Memorial Sloan-Kettering Cancer Center, New York, NY.
- Department of Medicine, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL.
- Department of Medicine, Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY.
- Department of Medicine, Weill Cornell Medical College, New York, NY.
- Leukemia Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY.
Abstract
Vemurafenib, an oral BRAF inhibitor, has demonstrated high response rates in relapsed/refractory (R/R) hairy cell leukemia (HCL). However, little is known about long-term outcomes and response to retreatment. Herein, we report the results of 36 patients with R/R HCL treated with vemurafenib from the United States arm of the phase 2 clinical trial (NCT01711632). The best overall response rate was 86%, including 33% complete response (CR) and 53% partial response (PR). After a median follow-up of 40 months, 21 of 31 responders (68%) experienced relapse with a median relapse-free survival (RFS) of 19 months (range, 12.5-53.9 months). There was no significant difference in the RFS for patients with CR vs PR. Fourteen of 21 (67%) relapsed patients were retreated with vemurafenib, with 86% achieving complete hematologic response. Two patients acquired resistance to vemurafenib with the emergence of new KRAS and CDKN2A mutations, respectively. Six of 12 (50%) responders to vemurafenib retreatment experienced another relapse with a median RFS of 12.7 months. Overall survival (OS) was 82% at 4 years, with a significantly shorter OS in patients who relapsed within 1 year of initial treatment with vemurafenib. Higher cumulative doses or a longer duration of treatment did not lengthen the durability of response. All adverse events in the retreatment cohort were grade 1/2 except for 1 case of a grade 3 rash and 1 grade 3 fever/pneumonia. Our data suggest that vemurafenib retreatment is a safe and effective option for patients with R/R HCL.
© 2022 by The American Society of Hematology.
Comment · 정정
Conflict of interest statement
Conflict-of-interest disclosure: R.M.S. has received advisory or consulting fees from AbbVie, Actinium, Agios, Arog, Astellas, Biolinerx, Celgene, Daiichi-Sankyo, Elevate, Gemoab, Janssen, Jazz, Macrogenics, Novartis, OncoNova, Syndax, Syntrix, Syros, Takeda, Trovagene, BergenBio, Foghorn Therapeutics, GSK, Aprea, Innate, Amgen, CTI Pharmaceuticals, BMS, and Boston Pharmaceuticals. A.S. serves as a consultant for AstraZeneca and Innate Pharmaceuticals. J.K.A. has received advisory or consulting fees from AbbVie, Amgen, Astellas, Daiichi Sankyo, Kura Oncology, Stemline, Syros, and Theradex; research funding at an institutional level for the conduct of trials from ALX Oncology, Amgen, Aptos, Astellas, Aprea, BioSight, BMS, Boehringer Ingelheim, Celgene, FujiFilm, Immunogen, Kartos, Kura Oncology, Loxo, and Takeda; reimbursement for travel from BioSight; and serves on a data monitoring committee for Glycomimetics. M.R.G. has received advisory or consulting fees from Pharmacyclics, AstraZeneca, and Sereno/Merck and serves on a data safety monitoring committee for Ascerta. J.T. has received honorarium from Karyopharm Therapeutics. O.A.-W. has served as a consultant for H3B Biomedicine, Foundation Medicine Inc, Merck, Prelude Therapeutics, and Janssen, and is on the Scientific Advisory Board of Envisagenics Inc., AIChemy, Harmonic Discovery Inc., and Pfizer Boulder and has received prior research funding from H3B Biomedicine, LOXO Oncology, and Nurix Therapeutics unrelated to the current manuscript. M.S.T. has received research funding from Abbvie, Cllerant, Orsenix, ADC Therapeutics, Biosight, Glycomimetics, Rafael Pharmaceuticals, and Amgen; has received advisory fees from AbbVie, BioLineRx, Daiichi-Sankyo, Orsenix, KAHR, Rigel, Nohla, Δ Fly Pharma, Tetraphase, Oncolyze, Jazz Pharma, Roche, Biosight, Novartis, Innate Pharmaceuticals, Kura, and Syros Pharmaceuticals; has consulted for Innate Phamaceuticals; and receives royalties from UpToDate. J.H.P. has received advisory or consulting fees from Allogene, Amgen, Artiva, Autolus, BMS, Curocel, Incyte, InnatePharma, Kite Pharma, Kura Oncology, Minerva, Novartis, Pfizer, PrecisionBio, and Servier and serves on a data monitoring committee for Affyimmune, BrightPharma, and Intellia. M.R.G. received research funding from Hairy Cell Leukemia Foundation and serves as Chair of Scientific Review Committee for Hairy Cell Leukemia Foundation (uncompensated). The remaining authors declare no competing financial interests.
그 밖의 정보
- 출판 형태
- Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
- 저널
- Blood · eISSN 1528-0020
- MeSH
- Humans · Vemurafenib / therapeutic use · Leukemia, Hairy Cell* / drug therapy / genetics · Proto-Oncogene Proteins B-raf / genetics · Protein Kinase Inhibitors / therapeutic use · Remission Induction · Antineoplastic Agents* / adverse effects
- Substances
- Vemurafenib · Proto-Oncogene Proteins B-raf · Protein Kinase Inhibitors · Antineoplastic Agents
- 연구비
- NCI NIH HHS P30 CA008748
- 데이터
- ClinicalTrials.gov: NCT01711632
- 참고문헌
- 30편