2010NCCN指南-多发性骨髓瘤

Continue NCCN Clinical Practice Guidelines in Oncology™ Multiple Myeloma V.2.2010 www.nccn.org Guidelines Index Multiple Myeloma TOC Discussion, References Practice Guidelines in Oncology – v.2.2010 Version 2.2010, 07/01/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. NCCN ® NCCN Multiple Myeloma Panel Members George Somlo, MD † ‡ Þ City of Hope Comprehensive Cancer Center Keith Stockerl-Goldstein, MD † Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine Guido Tricot, MD, PhD ‡ Huntsman Cancer Institute at the University of Utah Julie M. Vose, MD ‡ UNMC Eppley Cancer Center at the Nebraska Medical Center Donna Weber, MD † ‡ Þ The University of Texas M. D. Anderson Cancer Center Joachim Yahalom, MD § Memorial Sloan-Kettering Cancer Center Furhan Yunus, MD St. Jude Children’s Research Hospital/University of Tennessee Cancer Institute � � * Cristina Gasparetto, MD † Duke Comprehensive Cancer Center Carol Ann Huff, MD † The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Madan Jagasia, MD ‡ Vanderbilt-Ingram Cancer Center Bruno C. Medeiros, MD ‡ Stanford Comprehensive Cancer Center Ruby Meredith, MD, PhD § University of Alabama at Birmingham Comprehensive Cancer Center Noopur Raje, MD † ‡ Dana-Farber/Brigham and Women’s Cancer Center | Massachusetts General Hospital Cancer Center Jeffrey Schriber, MD ‡ City of Hope Comprehensive Cancer Center Seema Singhal, MD ‡ Robert H. Lurie Comprehensive Cancer Center of Northwestern University � � Continue Kenneth C. Anderson, MD/Chair ‡ Dana-Farber/Brigham and Women's Cancer Center | Massachusetts General Hospital Cancer Center Melissa Alsina, MD ‡ H. Lee Moffitt Cancer Center & Research Institute William Bensinger, MD † Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance J. Sybil Biermann, MD ¶ University of Michigan Comprehensive Cancer Center Asher Chanan-Khan, MD † Roswell Park Cancer Institute Adam D. Cohen, MD Fox Chase Cancer Center Steven Devine, MD The Ohio State University Comprehensive Cancer Center - James Cancer Center and Solove Research Institute Benjamin Djulbegovic, MD , PhD † ‡ H. Lee Moffitt Cancer Center & Research Institute � � † † Medical oncology ‡ Hematology Bone marrow transplantation ¶ Surgery/Surgical oncology § Radiotherapy/Radiation oncology € Pediatric oncology * Writing committee member � Þ Internal medicine Multiple Myeloma NCCN Guidelines Panel Disclosures Guidelines Index Multiple Myeloma TOC Discussion, References Practice Guidelines in Oncology – v.2.2010 Version 2.2010, 07/01/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. NCCN ® For help using these documents, please click here Discussion References Table of Contents Multiple Myeloma: Waldenström’s Macroglobulinemia: NCCN Multiple Myeloma Panel Members Guidelines Index Print the Multiple Myeloma Guidelines Summary of Guidelines Updates Osseous or Extraosseous Solitary Plasmacytoma: Primary Treatment (MYEL-2) Multiple Myeloma: Induction Therapy and Follow-up (MYEL-3) Definition of Multiple Myeloma (Smoldering and Active Myeloma) (MYEL-B) Systemic Light Chain Amyloidosis (AL-1) Workup and Primary Treatment (WALD-1) Surveillance and Follow-up (WALD-2) � � � � � � � � � � � � Diagnostic Workup and Clinical Presentations (MYEL-1) Follow-up and Surveilliance (MYEL-4) Active Disease: Additional Treatment for Progression (MYEL-6) Staging Systems for Multiple Myeloma (MYEL-A) Response Criteria for Multiple Myeloma (MYEL-C) Induction Therapy (MYEL-D) Adjunctive Treatment (MYEL-E) � These guidelines are a statement of evidence and consensus of the authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult these guidelines is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient's care or treatment. The National Comprehensive Cancer Network makes no representations nor warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way. These guidelines are copyrighted by National Comprehensive Cancer Network. All rights reserved. These guidelines and the illustrations herein may not be reproduced in any form without the express written permission of NCCN. ©2009. Clinical Trials: Categories of Evidence and Consensus: NCCN All recommendations are Category 2A unless otherwise specified. See The believes that the best management for any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. NCCN To find clinical trials online at NCCN member institutions, click here: nccn.org/clinical_trials/physician.html NCCN Categories of Evidence and Consensus Multiple Myeloma Guidelines Index Multiple Myeloma TOC Discussion, References Practice Guidelines in Oncology – v.2.2010 Version 2.2010, 07/01/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. NCCN ® Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. Summary of the Guidelines Updates UPDATES Multiple Myeloma Summary of major changes in the 1.2010 version of the NCCN Multiple Myeloma Guidelines from the 2.2009 version include : Initial Diagnostic Workup Unilateral bone marrow aspirate + biopsy, added “including bone marrow immunohistochemistry and /or bone marrow flow cytometry.” Deleted C-reactive protein from the “Useful under some circumstances” column. Footnote g: Added the IFM 99-03 trial where no overall survival or progression free survival advantage was seen with autologous transplant followed by mini allograft in high-risk myeloma patients (Garban et al, Blood 2006; 107:3474). NCCN Categories of Evidence and Consensus were revised on the following therapies: Primary induction therapy for transplant candidates: Bortezomib/dexamethasone category 1 previously category 2B Bortezomib/doxorubicin/dexamethasone category 1 previously category 2B Bortezomib/thalidomide/dexamethasone category 1 previously category 2B Dexamethasone category 2B previously category 2A Thalidomide/dexamethasone category 2B previously category 2A Primary induction therapy for non-transplant candidates: Dexamethasone category 2B previously category 2A Lenalidomide/low-dose dexamethasone category 1 previously category 2B Thalidomide/dexamethasone category 2B previously category 2A Vincristine/doxorubicin/dexamethasone (VAD) category 2B previously category 2A � � � � � � � � � � � MYEL-1 MYEL-4 MYEL-D � � � Lenalidomide/dexamethasone category 1 previously category 2B Liposomal doxorubicin/vincristine/dexamethasone (DVD) category 2B previously category 2A� � Summary of major changes in the 2.2010 version of the NCCN Multiple Myeloma Guidelines from the 1.2010 version include: The addition of the updated section.� Discussion Guidelines Index Multiple Myeloma TOC Discussion, References Practice Guidelines in Oncology – v.2.2010 Version 2.2010, 07/01/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. NCCN ® See Primary Treatment (MYEL-3) MYEL-1 Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. � � � � � � � � � � H&P CBC, differential, platelets BUN/creatinine, electrolytes Skeletal survey Unilateral bone marrow aspirate + biopsy, including bone marrow immunohistochemistry and/or bone marrow flow cytometry LDH Calcium/albumin microglobulin 24 h urine total protein Serum quantitative immunoglobulins, serum protein electrophoresis (SPEP), serum immunofixation electrophoresis (SIFE) 24 h urine for total protein, urine protein electrophoresis (UPEP), urine immunofixation electrophoresis (UIFE) � � � Beta-2 Cytogenetics FISH [del 13, del 17, t(4;14), t(11;14), t(14;16)] a b c d Includes Durie-Salmon Stage l myeloma. See Staging Systems for Multiple Myeloma (MYEL-A). Smoldering AsymptomaticSee Myeloma ( ) (MYEL-B). See Active Myeloma (Symptomatic) (MYEL-B). CLINICAL PRESENTATION Smoldering (a )symptomatic b,c Active (symptomatic)d Solitary plasmacytomaa See Osseous: Primary Treatment (MYEL-2) See Extraosseous: Primary Treatment (MYEL-2) Useful Under Some Circumstances � � � � � MRI for suspected compression CT scan (avoid contrast) Tissue biopsy to diagnose a solitary osseous or extraosseous plasmacytoma � � � � � PET/CT scan Bone densitometry Plasma cell labeling index Staining of marrow and fat pad for amyloid Serum free light chain assay Serum viscosity HLA typing vertebral INITIAL DIAGNOSTIC WORKUP Multiple Myeloma Guidelines Index Multiple Myeloma TOC Discussion, References Practice Guidelines in Oncology – v.2.2010 Version 2.2010, 07/01/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. NCCN ® MYEL-2 Solitary Osseous Solitary Extraosseous RT ( 45 Gy) to involved field � RT ( 45 Gy) to involved field and/or surgery � Restage with myeloma workup See Active (symptomatic) (MYEL-3) Primary progressivee or Response followed by progressione e .See Response Criteria for Multiple Myeloma (MYEL-C) Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. CLINICAL PRESENTATION PRIMARY TREATMENT FOLLOW-UP/SURVEILLANCE � � � � � � � � CBC Serum chemistry for creatinine, albumin, LDH, calcium, beta-2 microglobulin Consider serum free light chain assay 24 h urine for total protein, urine protein electrophoresis (UPEP), urine immunofixation electrophoresis (UIFE) Consider bone marrow biopsy as clinically indicated Consider bone survey as clinically indicated or annually Consider MRI and or CT and or PET/CT as clinically indicated or every 6-12 mo Serum quantitative immunoglobulins, serum protein electrophoresis (SPEP), serum immunofixation electrophoresis (SIFE) Multiple Myeloma Guidelines Index Multiple Myeloma TOC Discussion, References Practice Guidelines in Oncology – v.2.2010 Version 2.2010, 07/01/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. NCCN ® MYEL-3 Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. Observe at 3- 6 mo intervals (category 1) See Active (symptomatic) Myeloma below Progression to stage II or higher diseasee Induction therapy , bisphosphonates + adjunctive treatment as indicated f g g Response e No responsee Stem-cell harvest (adequate for 2 transplants), if candidate for transplantation (Refer for evaluation by stem cell transplant center) See Additional Treatment (MYEL-4) See Additional Treatment (MYEL-6) a b f g c d Includes Durie-Salmon Stage l myeloma. e See Staging Systems for Multiple Myeloma (MYEL-A Smoldering See Active (Symptomatic) Myeloma (MYEL-B) ). . See (Asymptomatic) Myeloma (MYEL-B See Response Criteria for Multiple Myeloma (MYEL-C See Myeloma Therapy (MYEL-D See Adjunctive Treatment (MYEL-E ). ). ). ). CLINICAL PRESENTATION INDUCTION THERAPY FOLLOW-UP/SURVEILLANCE Smoldering (a )symptomatic b,c Active (symptomatic)d � � � � � Quantitative immuno- globulins + quantitation of M protein CBC, differential, platelets BUN, creatinine, calcium Bone survey annually or for symptoms Bone marrow biopsy as clinically indicated Consider free light chain Consider MRI Consider PET/CT scan � � � (serum and urine) Multiple Myeloma Guidelines Index Multiple Myeloma TOC Discussion, References Practice Guidelines in Oncology – v.2.2010 Version 2.2010, 07/01/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. NCCN ® � � � � � Quantitative immunoglobulins + quantitation of M protein at least every 3 mo CBC, differential, platelets BUN, creatinine, calcium Bone survey annually or for symptoms Bone marrow biopsy as clinically indicated � � � Consider free light chain Consider MRI Consider PET/CT scan Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. Active (symptomatic) myeloma: Response after induction therapy h i A prospective trial by Bruno, et al. NEJM 356:1110-1120, found improved survival for patients receiving an autologous transplant followed by non-myeloablative allograft compared to patients who received tandem autologous grafts. The IFM trial (99-03) by Garban et al, Blood 2006; 107:3474, reported no overall survival or progression free survival with autologous transplant followed by mini allograft in high-risk myeloma patients. Allogeneic stem cell transplant may include nonmyeloablative (mini) following autologous stem cell transplant or fully myeloablative on a clinical trial (off-trial category 3). Single autologous transplantation: Category 1 evidence supports proceeding straight after induction therapy to high dose therapy and stem cell transplant versus saving the stem cell transplant for salvage therapy. Evidence suggests equivalent overall survival although progression free survival can be prolonged by an early transplant. Fermand JP, Katsahian S, Divine M, et al. High dose therapy and autologous blood stem cell transplantation compared with conventional treatment in myeloma patients aged 55 to 65 years: Long term results of a randomized control trial from the Group Myelome-Autogreffe. J Clin Oncol 2005;23:9227-9233. Barlogie B, Kyle RA, Anderson KC, et al. Comparable survival of patients with multiple myeloma treated with autotransplant-supported melphalan - TBI or standard VBMCP consolidation and no role of interferon maintenance: final results of US Intergroup Trial S9321. J Clin Oncol 2006;929-936. Renal dysfunction and advanced age are not contraindications to transplant. 2007; Current data do not support miniallografting alone. j Continue induction therapy to plateau Allogeneic stem cell transplant in clinical trial h Autologous stem cell transplant i,j OR OR Monitor as above and/or maintenance therapy (clinical trial preferred) MYEL-4 FOLLOW-UP/SURVEILLANCE Multiple Myeloma Post-allogeneic and Post-autologous stem cell transplant See Additional Treatment (MYEL-5) Post-induction therapy See Additional Treatment (MYEL-6) Guidelines Index Multiple Myeloma TOC Discussion, References Practice Guidelines in Oncology – v.2.2010 Version 2.2010, 07/01/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. NCCN ® Response or stable disease e Refractory diseasee Progressive diseasee Observe or maintenance therapyf Observe or Second tandem transplant or Maintenance therapyf Salvage therapy on or off clinical trial or Donor lymphocyte infusion f Salvage therapy on or off clinical trial or Allogeneic stem cell transplant on clinical trial or Additional autologous stem cell transplant on clinical trial (category 2B) f k Progressive diseasee Post-allogeneic stem cell transplant: Post-autologous stem cell transplant: e k . Allogeneic stem cell transplant may include nonmyeloablative (mini) following autologous stem cell transplant or fully myeloablative on a clinical trial (off-trial category 3). f Current data do not support miniallografting alone. See Response Criteria of Multiple Myeloma (MYEL-C See Myeloma Therapy (MYEL-D ) ). Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. Progressive diseasee MYEL-5 ADDITIONAL TREATMENT Salvage therapy on or off clinical trial or Allogeneic stem cell transplant on clinical trial (category 3 for conventional vs clinical trial) f k Stable diseasee Multiple Myeloma Guidelines Index Multiple Myeloma TOC Discussion, References Practice Guidelines in Oncology – v.2.2010 Version 2.2010, 07/01/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. NCCN ® ADDITIONAL TREATMENT MYEL-6 Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. Active (symptomatic) myeloma: Progressive diseasee Autologous stem cell transplant on or off clinical trial Salvage therapy on or off clinical trial or Allogeneic stem cell transplant on a clinical trial i f k or e k . Allogeneic stem cell transplant may include nonmyeloablative (mini) following autologous stem cell transplant or fully myeloablative on a clinical trial (off-trial category 3). . Single autologous transplantation: Category 1 evidence supports proceeding straight after induction therapy to high dose therapy and stem cell transplant versus saving the stem cell transplant for salvage therapy. Evidence suggests equivalent overall survival although progression free survival can be prolonged by an early transplant. Fermand JP, Katsahian S, Divine M, et al. High dose therapy and autologous blood stem cell transplantation compared with conventional treatment in myeloma patients aged 55 to 65 years: Long term results of a randomized control trial from the Group Myelome-Autogreffe. J Clin Oncol 2005;23:9227-9233. Barlogie B, Kyle RA, Anderson KC, et al. Comparable survival of patients with multiple myeloma treated with autotransplant-supported melphalan - TBI or standard VBMCP consolidation and no role of interferon maintenance: final results of US Intergroup Trial S9321. J Clin Oncol 2006;929-936. f i Current data do not support miniallografting alone See Response Criteria for Multiple Myeloma (MYEL-C See Myeloma Therapy (MYEL-D). ) Multiple Myeloma Relapse diseasee or progressive disease Transplant candidatei Autologous stem cell transplant (category 1) Post-induction therapy: Non-transplant candidate Salvage therapy on or off clinical trialf Progressive diseasee Palliative care (Se