Consensus opinion from an international group of experts on measurable residual disease in hairy cell leukemia

Farhad Ravandi¹, Robert J Kreitman², Enrico Tiacci³, Leslie Andritsos⁴, Versha Banerji^{5

6}, Jacqueline C Barrientos⁷, Seema A Bhat⁸, James S Blachly⁸, Alessandro Broccoli⁹, Timothy Call¹⁰, Dai Chihara¹¹, Claire Dearden¹², Judit Demeter¹³, Sasha Dietrich¹⁴, Monica Else¹⁵, Narendranath Epperla⁸, Brunangelo Falini³, Francesco Forconi^{16

17}, Douglas E Gladstone¹⁸, Alessandro Gozzetti¹⁹, Sunil Iyengar¹², James B Johnston²⁰, Jeffrey Jorgensen²¹, Gunnar Juliusson²², Francesco Lauria²³, Gerard Lozanski²⁴, Sameer A Parikh¹⁰, Jae H Park²⁵, Aaron Polliack²⁶, Graeme Quest²⁷, Tadeusz Robak²⁸, Kerry A Rogers⁸, Alan Saven²⁹, John F Seymour³⁰, Tamar Tadmor³¹, Martin S Tallman²⁵, Constantine S Tam³², Philip A Thompson³³, Xavier Troussard³⁴, Clive S Zent³⁵, Thorsten Zenz³⁶, Pier Luigi Zinzani⁹, Bernhard Wörmann³⁷, Kanti Rai⁷, Michael Grever⁸

Affiliations

¹ Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA. fravandi@mdanderson.org.
² Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, MD, USA.
³ Institute of Hematology, Department of Medicine and Surgery, University and Hospital of Perugia, Perugia, Italy.
⁴ University of New Mexico Comprehensive Cancer Center, Albuquerque, NM, USA.
⁵ Department of Internal Medicine & Biochemistry and Medical Genetics, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
⁶ CancerCare Manitoba Research Institute, CancerCare Manitoba, Winnipeg, MB, Canada.
⁷ Feinstein Institutes for Medical Research and Zucker School of Medicine at Hofstra/Northwell, New Hyde Park, NY, USA.
⁸ Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.
⁹ IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia "Seràgnoli"; and Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale Università di Bologna, Bologna, Italy.
¹⁰ Division of Hematology, Mayo Clinic, Rochester, MN, USA.
¹¹ Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
¹² The Royal Marsden NHS Foundation Trust, London, UK.
¹³ Department of Internal Medicine and Oncology, Semmelweis University, Budapest, Hungary.
¹⁴ Department of Hematology, University Hospital of Heidelberg, Heidelberg, Germany.
¹⁵ Division of Molecular Pathology, The Institute of Cancer Research, London, UK.
¹⁶ School of Cancer Sciences, Cancer Research UK Southampton Centre, Faculty of Medicine, University of Southampton, Southampton, UK.
¹⁷ Haematology Department, Cancer Care Directorate, University Hospital Southampton NHS Trust, Southampton, UK.
¹⁸ Johns Hopkins Kimmel Cancer Center Baltimore, Baltimore, MD, USA.
¹⁹ Dept. of Medicine, Surgery and Neurosciences, University of Siena, Policlinico S. Maria alle Scotte-, Siena, Italy.
²⁰ Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada.
²¹ Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
²² Lund University Stem Cell Center, Lund, Sweden.
²³ University of Siena, Siena, Italy.
²⁴ Department of Pathology, The Ohio State University Medical Center, Columbus, OH, USA.
²⁵ Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
²⁶ Hadassah University Hospital, Jerusalem, Israel.
²⁷ Kingston Health Sciences Centre, Canada, Canada.
²⁸ Department of Hematology, Medical University of Lodz, Lodz, Poland.
²⁹ Division of Hematology and Oncology, Scripps Clinic, La Jolla, CA, USA.
³⁰ Haematology Department, Peter MacCallum Cancer Centre & Royal Melbourne Hospital, University of Melbourne, Melbourne, VIC, Australia.
³¹ Hematology Unit, Bnai Zion Medical Center; and the Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel.
³² Department of Haematology, Alfred Hospital and Monash University, Melbourne, Victoria, Australia.
³³ Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
³⁴ Department of Hematology, Centre Hospitalier Universitaire Cote de Nacre, Caen, France.
³⁵ James P. Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA.
³⁶ Dept. of Medical Oncology and Haematology, University Hospital Zürich and University of Zurich (UZH), Zurich, Switzerland.
³⁷ The Charité - Universitätsmedizin Berlin, Berlin, Germany.

PMID: 36509740
PMCID: PMC9744664
DOI: 10.1038/s41408-022-00760-z

Review

Consensus opinion from an international group of experts on measurable residual disease in hairy cell leukemia

Farhad Ravandi et al. Blood Cancer J. 2022.

. 2022 Dec 13;12(12):165.

doi: 10.1038/s41408-022-00760-z.

Authors

Affiliations

¹ Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA. fravandi@mdanderson.org.
² Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, MD, USA.
³ Institute of Hematology, Department of Medicine and Surgery, University and Hospital of Perugia, Perugia, Italy.
⁴ University of New Mexico Comprehensive Cancer Center, Albuquerque, NM, USA.
⁵ Department of Internal Medicine & Biochemistry and Medical Genetics, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
⁶ CancerCare Manitoba Research Institute, CancerCare Manitoba, Winnipeg, MB, Canada.
⁷ Feinstein Institutes for Medical Research and Zucker School of Medicine at Hofstra/Northwell, New Hyde Park, NY, USA.
⁸ Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.
⁹ IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia "Seràgnoli"; and Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale Università di Bologna, Bologna, Italy.
¹⁰ Division of Hematology, Mayo Clinic, Rochester, MN, USA.
¹¹ Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
¹² The Royal Marsden NHS Foundation Trust, London, UK.
¹³ Department of Internal Medicine and Oncology, Semmelweis University, Budapest, Hungary.
¹⁴ Department of Hematology, University Hospital of Heidelberg, Heidelberg, Germany.
¹⁵ Division of Molecular Pathology, The Institute of Cancer Research, London, UK.
¹⁶ School of Cancer Sciences, Cancer Research UK Southampton Centre, Faculty of Medicine, University of Southampton, Southampton, UK.
¹⁷ Haematology Department, Cancer Care Directorate, University Hospital Southampton NHS Trust, Southampton, UK.
¹⁸ Johns Hopkins Kimmel Cancer Center Baltimore, Baltimore, MD, USA.
¹⁹ Dept. of Medicine, Surgery and Neurosciences, University of Siena, Policlinico S. Maria alle Scotte-, Siena, Italy.
²⁰ Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada.
²¹ Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
²² Lund University Stem Cell Center, Lund, Sweden.
²³ University of Siena, Siena, Italy.
²⁴ Department of Pathology, The Ohio State University Medical Center, Columbus, OH, USA.
²⁵ Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
²⁶ Hadassah University Hospital, Jerusalem, Israel.
²⁷ Kingston Health Sciences Centre, Canada, Canada.
²⁸ Department of Hematology, Medical University of Lodz, Lodz, Poland.
²⁹ Division of Hematology and Oncology, Scripps Clinic, La Jolla, CA, USA.
³⁰ Haematology Department, Peter MacCallum Cancer Centre & Royal Melbourne Hospital, University of Melbourne, Melbourne, VIC, Australia.
³¹ Hematology Unit, Bnai Zion Medical Center; and the Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel.
³² Department of Haematology, Alfred Hospital and Monash University, Melbourne, Victoria, Australia.
³³ Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
³⁴ Department of Hematology, Centre Hospitalier Universitaire Cote de Nacre, Caen, France.
³⁵ James P. Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA.
³⁶ Dept. of Medical Oncology and Haematology, University Hospital Zürich and University of Zurich (UZH), Zurich, Switzerland.
³⁷ The Charité - Universitätsmedizin Berlin, Berlin, Germany.

PMID: 36509740
PMCID: PMC9744664
DOI: 10.1038/s41408-022-00760-z

Abstract

A significant body of literature has been generated related to the detection of measurable residual disease (MRD) at the time of achieving complete remission (CR) in patients with hairy cell leukemia (HCL). However, due to the indolent nature of the disease as well as reports suggesting long-term survival in patients treated with a single course of a nucleoside analog albeit without evidence of cure, the merits of detection of MRD and attempts to eradicate it have been debated. Studies utilizing novel strategies in the relapse setting have demonstrated the utility of achieving CR with undetectable MRD (uMRD) in prolonging the duration of remission. Several assays including immunohistochemical analysis of bone marrow specimens, multi-parameter flow cytometry and molecular assays to detect the mutant BRAF V600E gene or the consensus primer for the immunoglobulin heavy chain gene (IGH) rearrangement have been utilized with few comparative studies. Here we provide a consensus report on the available data, the potential merits of MRD assessment in the front-line and relapse settings and recommendations on future role of MRD assessment in HCL.

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Conflict of interest statement

FR: Consultancy and Honoraria: Celgene, BMS, Amgen, Astellas, Xencor, Agios, AstraZeneca, Orsenix, Innate Pharma, Syros, Taiho, Novartis; Research Funding: BMS, Amgen, Xencor, Macrogenics, Orsenix, AbbVie, Taiho, Prelude, Astex. RK: Employment: National Institutes of Health and Regional Cancer Care Associates; Honoraria: PlatformQ, OncLive, Cure; Research Funding: Innate, AstraZeneca, Novartis, Genetech, Pfizer, Teva, Hairy Cell Leukemia Foundation; and Patents: Coinventor for NIH patent for Moxetumomab Pasudotox. EI: Consultant: Innate Pharma. Research funding: Roche. Travel cost: Shire. Holder of a patent on the use of mutant BRAF as HCL biomarker. Our research work in HCL is funded by the Hairy Cell Leukemia Foundation, the Leukemia and Lymphoma Society and the Associazione Italiana Ricerca sul Cancro (AIRC). LA: None. VB: VB serves on the advisory boards of Janssen, Astra Zeneca, AbbVie, and Beigene and has had research funding from CIHR, LLSC, CCMF, Roche, Janssen, and AbbVie. VB also received fees from BIOGEN for patented compounds unrelated to this study. JB: Research funding: AstraZeneca, Oncternal, TG therapeutics, Pharmacyclics/AbbVie; and Advisory Board: AstraZeneca, Pharmacyclics/AbbVie, Beigene, Genentech, Gilead, Innate. SB: Served on Advisory board for Pharmacyclics and Janssen, Beigene and AstraZeneca; Received honorarium from OncLive; and Received travel grant from Arqule. JB: Consulting and Advisory Board: AbbVie, AstraZeneca, INNATE Pharma, KITE Pharma; Research funding: MingSight Pharmaceuticals; and Patents and Intellectual Property: A leukemia diagnostic device (patent pending). AB: None reported. TC: None reported. DC: None reported. CD: Has been an advisor for Medimmune/ Innate Pharma (moxetumomab); Consulting/ Advisory board for AbbVie and Jansen. JD: Has participated in advisory committees in Hungary for Novartis, Bristol Myers Squibb, Amicus, Angelini, Pfizer, Amgen, Roche. SD: None reported. ME: None reported. BF: None reported. FF: Research Support/P.I.: CRUK, Blood Cancer UK; Consultancies: AstraZeneca, AbbVie, Janssen-Cilag, BC-Platform, Beigene; Speakers Bureau: AstraZeneca, AbbVie; and Honoraria: AstraZeneca, AbbVie. DG: None reported. AG: Honoraria: Jansenn and AbbVie. SI: Advisory and speaker fees: Gilead and Takeda; Advisory: Beigene; and Speaker fees: Janssen, Takeda and Gilead. JBJ: None reported. JJ: None reported. GJ: None reported. FL: None reported. GL: None reported. SP: Research funding to the institution from Pharmacyclics, Janssen, AstraZeneca, TG Therapeutics, Merck, AbbVie, and Ascentage Pharma for clinical studies in which Sameer A. Parikh is a principal investigator. Sameer A. Parikh has received honoraria for participation in consulting activities/advisory board meetings for Pharmacyclics, Merck, AstraZeneca, Genentech, GlaxoSmithKline, Adaptive Biotechnologies, and AbbVie (no personal compensation), and from DynaMed, Aptitude Health, Curio Science, and MedEd on the Go (with personal compensation). JP: Research funding from Genentech, Servier, Takeda, Fate Therapeutics and Amgen; Consulting fees from Servier, Amgen, AstraZeneca, Innate Pharma, Novartis, Kite Pharma, Takeda, Intellia, Kura Oncology, Pfizer, BMS, Curocel, Minerva, Autolus; serves on DSMB for Affyimmune and BrightPharma; serves on Scientific Advisory Board for Allogene and Artiva. AP: None reported. GQ: None reported. TR: Honoraria: Sandoz, BeiGene, AstraZeneca; Advisory/Consulting: Jannssen, AstraZeneca, Takeda, BeiGene; and Research Funding: AstraZeneca (ongoing), Acerta (ongoing), Janssen (ongoing). KAR: Research funding: Genentech, AbbVie, Novartis, and Janssen; Consulting: Acerta Pharma, AstraZeneca, Innate Pharma, Genentech, AbbVie, Pharmacyclics, and Beigene; and Travel funding: AstraZeneca. AS: None reported. JS: AbbVie: Advisory board, speakers’ bureau, research funding; Astra Zeneca: Advisory board; Celgene: Advisory board, speakers’ bureau, research funding, expert testimony; Genentech: Advisory board; Gilead: Advisory Board; Janssen: Advisory board, research funding; Mei Pharma: Advisory board; Morphosys, Advisory board; Roche, Advisory board, speakers’ bureau, research funding, expert testimony; Sunesis, Advisory board; Takeda, Advisory board. TT: Grant from Janssen; Advisory Board/Consulting: AbbVie, Janssen, Astra Zeneca, Roche, Novartis, Takeda, and Sanofi. MT: Research funding: AbbVie, Amgen, Biosight, Glycomimetics, Orsenix, Rafael; Advisory boards: Amgen, Daiichi-Sankyo, Innate pharmaceuticals, Jazz, Kahr, Kura, Novartis, Orsenix, Roche, Syros, Ipsen Biopharmaceuticals, and Oncolyze; and Royalties: UpToDate. CT: Honorarium: Beigene, Novartis, LOXO, AbbVie, Janssen; Research funding: Beigene, AbbVie, Janssen. PT: Research Funding: AbbVie, Pharmacyclics, Genentech, Adaptive Biotechnologies; Consultancy: Janssen, Genentech, Adaptive Biotechnologies, AbbVie; Lecture fees: Janssen. XT: Consultant for Innate Pharma, AstraZeneca and Beigene; Advisor for AbbVie. CZ: Research funding to University of Rochester from Acerta/AstraZeneca and TG Therapeutics. TZ: Roche, Innate, Incyte, AbbVie, Gilead, Janssen (honoraria). PLZ: Advisory Board Member: Secura Bio, Celltrion, Gilead, Janssen-Cilag, BMS, Servier, Sandoz, MSD, TG Therapeutics, Takeda, Roche, Eusapharma, Kyowa Kirin, Novartis, ADC Therapeutics, Incyte, Beigene; Speakers Bureau: Celltrion, Gilead, Janssen-Cilag, BMS, Servier, MSD, TG Therapeutics, Takeda, Roche, Eusapharma, Kyowa Kirin, Novartis, Incyte, Beigene; Consultant: MSD, Eusapharma, Novartis. BW: None reported. KR: None reported. MG: Consultant: Astra Zeneca, Pharmacyclics, Ascerta, Axio, Inc; Research Funding: Hairy Cell Leukemia Foundation for Patient Data Registry; Travel Expenses: Hairy Cell Leukemia Foundation; Scientific Board: Chair, Hairy Cell Leukemia Foundation Scientific Board (no reimbursement); and Scientific Honorarium: University of Pittsburgh.

Figures

**Fig. 1**
Achievement of MRD negative status by MFC after moxetumomab was associated with prolonged CR duration (Adapted from Kreitman R, et al, J Hematol Oncol, 2021). MRD negativity was associated with durable CR.

**Fig. 2**
Relapse-free survival by MRD status among patients treated with vemurafenib plus rituximab. (Adapted from Tiacci E, et al, NEJM, 2021).

See this image and copyright information in PMC

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Consensus opinion from an international group of experts on measurable residual disease in hairy cell leukemia

Affiliations

Consensus opinion from an international group of experts on measurable residual disease in hairy cell leukemia

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Research Materials