title: Recommendations for Clinical Trial Development in Mantle Cell Lymphoma.
abstract: Mantle cell lymphoma (MCL) comprises around 6% of all non-Hodgkin's lymphoma (NHL) diagnoses. In younger patients, age less than 60 to 65 years, aggressive induction often followed by consolidation with autologous stem cell transplant has suggested improved outcomes in this population. Less intensive therapies in older patients often followed by maintenance have been studied or are under active investigation. However, despite recent advances, MCL remains incurable, with a median overall survival of around five years. Patients with high-risk disease have particularly poor outcomes. Treatment varies widely across institutions, and to date no randomized trials comparing intensive vs less intensive approaches have been reported. Although recent data have highlighted the heterogeneity of MCL outcomes, patient assessment for treatment selection has largely been driven by patient age with little regard to fitness, disease biology, or disease risk. One critical advance is the finding that minimal residual disease status (MRD) after induction correlates with long-term outcomes. As such, its use as a potential end point could inform clinical trial design. In order to more rapidly improve the outcomes of MCL patients, clinical trials are needed that prospectively stratify patients on the basis of MCL biology and disease risk, incorporate novel agents, and use MRD to guide the need for additional therapy.
authors.affiliation: Affiliations of authors: Division of Hematology and Medical Oncology, Oregon Health and Science (OHSU) University Knight Cancer Institute, Portland, OR (SES); Clinical Research Division, Fred Hutchinson Cancer Research Center/ Department of Medicine, Division of Medical Oncology, University of Washington, Seattle, WA (BGT, AKG); Department of Medicine, Weill Cornell Medicine, New York, NY (PM, JPL); John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ (AHG); Department of Medicine III, Klinikum der Universität München, Campus Grosshadern, Munich, Germany (MPD); Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (ML); Wilmot Cancer Center and Division of Hematology/Oncology, University of Rochester, Rochester, NY (JWF); Coordinating Center for Clinical Trials, National Cancer Institute, National Institutes of Health, Bethesda, MD (LB); HIV and AIDS Malignancy Branch, Center for Cancer Research, and Clinical Investigations Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD (RFL); Department of Medicine, Oncology Division, Washington University, St. Louis, MO (BSK); Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH (MRS).
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Spurgeon
authors.affiliation: Affiliations of authors: Division of Hematology and Medical Oncology, Oregon Health and Science (OHSU) University Knight Cancer Institute, Portland, OR (SES); Clinical Research Division, Fred Hutchinson Cancer Research Center/ Department of Medicine, Division of Medical Oncology, University of Washington, Seattle, WA (BGT, AKG); Department of Medicine, Weill Cornell Medicine, New York, NY (PM, JPL); John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ (AHG); Department of Medicine III, Klinikum der Universität München, Campus Grosshadern, Munich, Germany (MPD); Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (ML); Wilmot Cancer Center and Division of Hematology/Oncology, University of Rochester, Rochester, NY (JWF); Coordinating Center for Clinical Trials, National Cancer Institute, National Institutes of Health, Bethesda, MD (LB); HIV and AIDS Malignancy Branch, Center for Cancer Research, and Clinical Investigations Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD (RFL); Department of Medicine, Oncology Division, Washington University, St. Louis, MO (BSK); Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH (MRS).
authors.forename: Brian G
authors.initials: BG
authors.lastname: Till
authors.affiliation: Affiliations of authors: Division of Hematology and Medical Oncology, Oregon Health and Science (OHSU) University Knight Cancer Institute, Portland, OR (SES); Clinical Research Division, Fred Hutchinson Cancer Research Center/ Department of Medicine, Division of Medical Oncology, University of Washington, Seattle, WA (BGT, AKG); Department of Medicine, Weill Cornell Medicine, New York, NY (PM, JPL); John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ (AHG); Department of Medicine III, Klinikum der Universität München, Campus Grosshadern, Munich, Germany (MPD); Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (ML); Wilmot Cancer Center and Division of Hematology/Oncology, University of Rochester, Rochester, NY (JWF); Coordinating Center for Clinical Trials, National Cancer Institute, National Institutes of Health, Bethesda, MD (LB); HIV and AIDS Malignancy Branch, Center for Cancer Research, and Clinical Investigations Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD (RFL); Department of Medicine, Oncology Division, Washington University, St. Louis, MO (BSK); Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH (MRS).
authors.forename: Peter
authors.initials: P
authors.lastname: Martin
authors.affiliation: Affiliations of authors: Division of Hematology and Medical Oncology, Oregon Health and Science (OHSU) University Knight Cancer Institute, Portland, OR (SES); Clinical Research Division, Fred Hutchinson Cancer Research Center/ Department of Medicine, Division of Medical Oncology, University of Washington, Seattle, WA (BGT, AKG); Department of Medicine, Weill Cornell Medicine, New York, NY (PM, JPL); John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ (AHG); Department of Medicine III, Klinikum der Universität München, Campus Grosshadern, Munich, Germany (MPD); Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (ML); Wilmot Cancer Center and Division of Hematology/Oncology, University of Rochester, Rochester, NY (JWF); Coordinating Center for Clinical Trials, National Cancer Institute, National Institutes of Health, Bethesda, MD (LB); HIV and AIDS Malignancy Branch, Center for Cancer Research, and Clinical Investigations Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD (RFL); Department of Medicine, Oncology Division, Washington University, St. Louis, MO (BSK); Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH (MRS).
authors.forename: Andre H
authors.initials: AH
authors.lastname: Goy
authors.affiliation: Affiliations of authors: Division of Hematology and Medical Oncology, Oregon Health and Science (OHSU) University Knight Cancer Institute, Portland, OR (SES); Clinical Research Division, Fred Hutchinson Cancer Research Center/ Department of Medicine, Division of Medical Oncology, University of Washington, Seattle, WA (BGT, AKG); Department of Medicine, Weill Cornell Medicine, New York, NY (PM, JPL); John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ (AHG); Department of Medicine III, Klinikum der Universität München, Campus Grosshadern, Munich, Germany (MPD); Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (ML); Wilmot Cancer Center and Division of Hematology/Oncology, University of Rochester, Rochester, NY (JWF); Coordinating Center for Clinical Trials, National Cancer Institute, National Institutes of Health, Bethesda, MD (LB); HIV and AIDS Malignancy Branch, Center for Cancer Research, and Clinical Investigations Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD (RFL); Department of Medicine, Oncology Division, Washington University, St. Louis, MO (BSK); Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH (MRS).
authors.forename: Martin P
authors.initials: MP
authors.lastname: Dreyling
authors.affiliation: Affiliations of authors: Division of Hematology and Medical Oncology, Oregon Health and Science (OHSU) University Knight Cancer Institute, Portland, OR (SES); Clinical Research Division, Fred Hutchinson Cancer Research Center/ Department of Medicine, Division of Medical Oncology, University of Washington, Seattle, WA (BGT, AKG); Department of Medicine, Weill Cornell Medicine, New York, NY (PM, JPL); John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ (AHG); Department of Medicine III, Klinikum der Universität München, Campus Grosshadern, Munich, Germany (MPD); Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (ML); Wilmot Cancer Center and Division of Hematology/Oncology, University of Rochester, Rochester, NY (JWF); Coordinating Center for Clinical Trials, National Cancer Institute, National Institutes of Health, Bethesda, MD (LB); HIV and AIDS Malignancy Branch, Center for Cancer Research, and Clinical Investigations Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD (RFL); Department of Medicine, Oncology Division, Washington University, St. Louis, MO (BSK); Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH (MRS).
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Gopal
authors.affiliation: Affiliations of authors: Division of Hematology and Medical Oncology, Oregon Health and Science (OHSU) University Knight Cancer Institute, Portland, OR (SES); Clinical Research Division, Fred Hutchinson Cancer Research Center/ Department of Medicine, Division of Medical Oncology, University of Washington, Seattle, WA (BGT, AKG); Department of Medicine, Weill Cornell Medicine, New York, NY (PM, JPL); John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ (AHG); Department of Medicine III, Klinikum der Universität München, Campus Grosshadern, Munich, Germany (MPD); Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (ML); Wilmot Cancer Center and Division of Hematology/Oncology, University of Rochester, Rochester, NY (JWF); Coordinating Center for Clinical Trials, National Cancer Institute, National Institutes of Health, Bethesda, MD (LB); HIV and AIDS Malignancy Branch, Center for Cancer Research, and Clinical Investigations Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD (RFL); Department of Medicine, Oncology Division, Washington University, St. Louis, MO (BSK); Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH (MRS).
authors.forename: Michael
authors.initials: M
authors.lastname: LeBlanc
authors.affiliation: Affiliations of authors: Division of Hematology and Medical Oncology, Oregon Health and Science (OHSU) University Knight Cancer Institute, Portland, OR (SES); Clinical Research Division, Fred Hutchinson Cancer Research Center/ Department of Medicine, Division of Medical Oncology, University of Washington, Seattle, WA (BGT, AKG); Department of Medicine, Weill Cornell Medicine, New York, NY (PM, JPL); John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ (AHG); Department of Medicine III, Klinikum der Universität München, Campus Grosshadern, Munich, Germany (MPD); Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (ML); Wilmot Cancer Center and Division of Hematology/Oncology, University of Rochester, Rochester, NY (JWF); Coordinating Center for Clinical Trials, National Cancer Institute, National Institutes of Health, Bethesda, MD (LB); HIV and AIDS Malignancy Branch, Center for Cancer Research, and Clinical Investigations Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD (RFL); Department of Medicine, Oncology Division, Washington University, St. Louis, MO (BSK); Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH (MRS).
authors.forename: John P
authors.initials: JP
authors.lastname: Leonard
authors.affiliation: Affiliations of authors: Division of Hematology and Medical Oncology, Oregon Health and Science (OHSU) University Knight Cancer Institute, Portland, OR (SES); Clinical Research Division, Fred Hutchinson Cancer Research Center/ Department of Medicine, Division of Medical Oncology, University of Washington, Seattle, WA (BGT, AKG); Department of Medicine, Weill Cornell Medicine, New York, NY (PM, JPL); John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ (AHG); Department of Medicine III, Klinikum der Universität München, Campus Grosshadern, Munich, Germany (MPD); Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (ML); Wilmot Cancer Center and Division of Hematology/Oncology, University of Rochester, Rochester, NY (JWF); Coordinating Center for Clinical Trials, National Cancer Institute, National Institutes of Health, Bethesda, MD (LB); HIV and AIDS Malignancy Branch, Center for Cancer Research, and Clinical Investigations Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD (RFL); Department of Medicine, Oncology Division, Washington University, St. Louis, MO (BSK); Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH (MRS).
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Friedberg
authors.affiliation: Affiliations of authors: Division of Hematology and Medical Oncology, Oregon Health and Science (OHSU) University Knight Cancer Institute, Portland, OR (SES); Clinical Research Division, Fred Hutchinson Cancer Research Center/ Department of Medicine, Division of Medical Oncology, University of Washington, Seattle, WA (BGT, AKG); Department of Medicine, Weill Cornell Medicine, New York, NY (PM, JPL); John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ (AHG); Department of Medicine III, Klinikum der Universität München, Campus Grosshadern, Munich, Germany (MPD); Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (ML); Wilmot Cancer Center and Division of Hematology/Oncology, University of Rochester, Rochester, NY (JWF); Coordinating Center for Clinical Trials, National Cancer Institute, National Institutes of Health, Bethesda, MD (LB); HIV and AIDS Malignancy Branch, Center for Cancer Research, and Clinical Investigations Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD (RFL); Department of Medicine, Oncology Division, Washington University, St. Louis, MO (BSK); Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH (MRS).
authors.forename: Lawrence
authors.initials: L
authors.lastname: Baizer
authors.affiliation: Affiliations of authors: Division of Hematology and Medical Oncology, Oregon Health and Science (OHSU) University Knight Cancer Institute, Portland, OR (SES); Clinical Research Division, Fred Hutchinson Cancer Research Center/ Department of Medicine, Division of Medical Oncology, University of Washington, Seattle, WA (BGT, AKG); Department of Medicine, Weill Cornell Medicine, New York, NY (PM, JPL); John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ (AHG); Department of Medicine III, Klinikum der Universität München, Campus Grosshadern, Munich, Germany (MPD); Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (ML); Wilmot Cancer Center and Division of Hematology/Oncology, University of Rochester, Rochester, NY (JWF); Coordinating Center for Clinical Trials, National Cancer Institute, National Institutes of Health, Bethesda, MD (LB); HIV and AIDS Malignancy Branch, Center for Cancer Research, and Clinical Investigations Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD (RFL); Department of Medicine, Oncology Division, Washington University, St. Louis, MO (BSK); Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH (MRS).
authors.forename: Richard F
authors.initials: RF
authors.lastname: Little
authors.affiliation: Affiliations of authors: Division of Hematology and Medical Oncology, Oregon Health and Science (OHSU) University Knight Cancer Institute, Portland, OR (SES); Clinical Research Division, Fred Hutchinson Cancer Research Center/ Department of Medicine, Division of Medical Oncology, University of Washington, Seattle, WA (BGT, AKG); Department of Medicine, Weill Cornell Medicine, New York, NY (PM, JPL); John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ (AHG); Department of Medicine III, Klinikum der Universität München, Campus Grosshadern, Munich, Germany (MPD); Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (ML); Wilmot Cancer Center and Division of Hematology/Oncology, University of Rochester, Rochester, NY (JWF); Coordinating Center for Clinical Trials, National Cancer Institute, National Institutes of Health, Bethesda, MD (LB); HIV and AIDS Malignancy Branch, Center for Cancer Research, and Clinical Investigations Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD (RFL); Department of Medicine, Oncology Division, Washington University, St. Louis, MO (BSK); Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH (MRS).
authors.forename: Brad S
authors.initials: BS
authors.lastname: Kahl
authors.affiliation: Affiliations of authors: Division of Hematology and Medical Oncology, Oregon Health and Science (OHSU) University Knight Cancer Institute, Portland, OR (SES); Clinical Research Division, Fred Hutchinson Cancer Research Center/ Department of Medicine, Division of Medical Oncology, University of Washington, Seattle, WA (BGT, AKG); Department of Medicine, Weill Cornell Medicine, New York, NY (PM, JPL); John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ (AHG); Department of Medicine III, Klinikum der Universität München, Campus Grosshadern, Munich, Germany (MPD); Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (ML); Wilmot Cancer Center and Division of Hematology/Oncology, University of Rochester, Rochester, NY (JWF); Coordinating Center for Clinical Trials, National Cancer Institute, National Institutes of Health, Bethesda, MD (LB); HIV and AIDS Malignancy Branch, Center for Cancer Research, and Clinical Investigations Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD (RFL); Department of Medicine, Oncology Division, Washington University, St. Louis, MO (BSK); Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH (MRS).
authors.forename: Mitchell R
authors.initials: MR
authors.lastname: Smith
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D015415:Biomarkers; D002986:Clinical Trials as Topic; D060830:Consolidation Chemotherapy; D023381:Endpoint Determination; D006801:Humans; D060828:Induction Chemotherapy; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy*; D060046:Maintenance Chemotherapy; D018365:Neoplasm, Residual; D012107:Research Design
chemical_list: D015415:Biomarkers