NCCN Guidelines Index SLC Amyloidosis TOC Discussion NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines® ) Systemic Light Chain Amyloidosis Version 2.2014 NCCN.org Continue Version 2.2014, 10/04/13 © National Comprehensive Cancer Network, Inc. 2013, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®. NCCN Guidelines® Version 2.2014 NCCN Guidelines Index SLC Amyloidosis TOC Systemic Light Chain Amyloidosis- Panel Members Discussion * Kenneth C. Anderson, MD/Chair ‡ Cristina Gasparetto, MD † Seema Singhal, MD ‡ Dana-Farber/Brigham and Women's Duke Cancer Institute Robert H. Lurie Comprehensive Cancer Cancer Center | Massachusetts General Center of Northwestern University Hospital Cancer Center Francisco Hernandez-Ilizaliturri, MD † Roswell Park Cancer Institute George Somlo, MD † ‡ Þ * William Bensinger, MD/Vice-Chair † x City of Hope Comprehensive Cancer Center Fred Hutchinson Cancer Research Center/ Carol Ann Huff, MD † Seattle Cancer Care Alliance The Sidney Kimmel Comprehensive *Keith Stockerl-Goldstein, MD † x Cancer Center at Johns Hopkins Siteman Cancer Center at Barnes-Jewish Hospital Melissa Alsina, MD ‡ and Washington University School of Medicine Moffitt Cancer Center Adetola Kassim, MD, MS ‡ x Vanderbilt-Ingram Cancer Center Steven P. Treon, MD, PhD † J. Sybil Biermann, MD ¶ Dana-Farber/Brigham and Women's University of Michigan Amrita Y. Krishnan, MD ‡ Cancer Center | Massachusetts General Comprehensive Cancer Center City of Hope Comprehensive Cancer Center Hospital Cancer Center Jason C. Chandler, MD † Michaela Liedtke, MD ‡ Donna Weber, MD † ‡ Þ St. Jude Children’s Research Hospital/ Stanford Cancer Institute The University of Texas The University of Tennessee Health MD Anderson Cancer Center Science Center Matthew Lunning, MD † Fred & Pamela Buffet Cancer Center at The Joachim Yahalom, MD § Caitlin Costello, MD †‡x Nebraska Medical Center Memorial Sloan-Kettering Cancer Center UC San Diego Moores Cancer Center Ruby Meredith, MD, PhD § Steven Devine, MD † University of Alabama at Birmingham The Ohio State University Comprehensive Comprehensive Cancer Center Cancer Center - James Cancer Hospital and Solove Research Institute Noopur Raje, MD † ‡ Dana-Farber/Brigham and Women’s Benjamin Djulbegovic, MD, PhD † ‡ x Cancer Center | Massachusetts General Moffitt Cancer Center Hospital Cancer Center † Medical oncology ‡ Hematology x Bone marrow transplantation NCCN Staff ¶ Surgery/Surgical oncology Rashmi Kumar, PhD Continue § Radiotherapy/Radiation oncology Dorothy A. Shead, MS € Pediatric oncology Þ Internal medicine * Writing committee member NCCN Guidelines Panel Disclosures Version 2.2014, 10/04/13 © National Comprehensive Cancer Network, Inc. 2013, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®. NCCN Guidelines Version 2.2014 NCCN Guidelines Index SLC Amyloidosis TOC Systemic Light Chain Amyloidosis- Table of Contents Discussion NCCN Systemic Light Chain Amyloidosis Panel Members Clinical Trials: NCCN believes that the best management for any cancer Updates patient is in a clinical trial. Participation in clinical trials is especially encouraged. Initial Diagnostic Workup (AMYL-1) To find clinical trials online at NCCN Member Institutions, click here: Clinical Findings and Primary Treatment (AMYL-2) nccn.org/clinical_trials/physician.html. NCCN Categories of Evidence and Primary Treatment References (AMYL-A) Consensus: All recommendations are category 2A unless otherwise specified. Organ Involvement and Response to Treatment Based See NCCN Categories of Evidence and Consensus on Amyloidosis Consensus Criteria (AMYL-B) The NCCN 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 the NCCN 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®® (NCCN ) makes no representations or warranties of any kind regarding their content, use or application and disclaims any responsibility for their application or use in any way. The NCCN Guidelines are copyrighted by National Comprehensive Cancer Network® . All rights reserved. The NCCN Guidelines and the illustrations herein may not Versionbe reproduced 2.2014, 10/04/13 © Nationalin any Comprehensive form without Cancer Network, the Inc.express 2013, All rights written reserved. permission The NCCN Guidelines of® and NCCN. this illustration ©2013. may not be reproduced in any form without the express written permission of NCCN®. NCCN Guidelines Version 2.2014 NCCN Guidelines Index SLC Amyloidosis TOC Systemic Light Chain Amyloidosis - Updates Discussion Updates in Version 2.2014 of the NCCN Guidelines for Systemic Light Chain Amyloidosis from Version 1.2014 include: MS-1 · The addition of the discussion to reflect the changes in the algorithm. Updates in Version 1.2014 of the NCCN Guidelines for Systemic Light Chain Amyloidosis from Version 1.2013 include: AMYL-2 · Added the following regimens to the list of primary treatment options: > Lenalidomide/cyclophosphamide/dexamethasone > Pomalidomide/dexamethasone AMYL-A · Added a reference page for the primary treatment regimens listed on AMYL-2. AMYL-B · (page 2 of 2) Corrected very good partial response criteria from “dFLC <40 mg/dL” to “dFLC <40mg/L.” 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. Version 2.2014, 10/04/13 © National Comprehensive Cancer Network, Inc. 2013, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®. UPDATES NCCN Guidelines Version 2.2014 NCCN Guidelines Index SLC Amyloidosis TOC Systemic Light Chain Amyloidosis Discussion INITIAL DIAGNOSTIC WORKUP Clinical and amyloid-related assessment: Special testing based on organ system involvement: · Orthostatic vital signs · Cardiac · History and physical > EKG > Echocardiogram Laboratory evaluation (directed toward commonly affected > Cardiac MRI (in certain circumstances) > organ systems): Chest x-ray · · CBC with differential Liver and GI tract > · Prothrombin time (PT), Partial thromboplastin time (PTT), Stool guaiacs > Gastric emptying scan (if gastroparesis present) Factor X (if indicated) > Ultrasound or CT scan to document craniocaudal · Hereditary amyloid testing (for African-American and liver span peripheral neuropathy patients at minimum) · · Peripheral nervous system Electrophoresis of serum and urine > EMG (if clinically significant peripheral · See Clinical Immunoelectrophoresis of serum and urine neuropathy) Findings (AMYL-2) · Serum-free light chains > Nerve conduction studies · 24-hour urinary protein and creatinine clearance · Other · Blood urea nitrogen, creatinine > Endocrine testing: TSH, cortisol · Brain natriuretic peptide (BNP) or NT-proBNP, troponin > Pulmonary testing: Pulmonary function tests · Alkaline phosphatase, liver enzymes, bilirubin Pathologic evaluation:a,b · Bone marrow aspirate and biopsy with immunohistochemical staining for kappa and lambda and Congo red staining for amyloid · Abdominal fat pad aspirate or involved organ biopsy as clinically indicated · Mass spectrometry as clinically indicated aIt is essential to confirm that patients have primary systemic amyloidosis rather than hereditary amyloidosis, senile amyloidosis, or secondary amyloidosis. The amyloid deposits should be confirmed to be composed of light chains using immunohistochemistry or mass spectrometry. Immunohistochemistry for transthyretin or serum amyloid A component should be performed if kappa and lambda stains are negative. bIdentification of light chains in the serum or urine without confirmation of the amyloid composition in tissue is not adequate as patients with other forms of amyloidosis may have an unrelated MGUS. Lachmann HJ, Booth DR, Booth SE, et al. Misdiagnosis of hereditary amyloidosis as AL (primary) amyloidosis. N Engl J Med 2002;346:1786-1791. 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. Version 2.2014, 10/04/13 © National Comprehensive Cancer Network, Inc. 2013, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®. AMYL-1 NCCN Guidelines Version 2.2014 NCCN Guidelines Index SLC Amyloidosis TOC Systemic Light Chain Amyloidosis Discussion CLINICAL FINDINGS PRIMARY TREATMENTc There are insufficient data to indicate the optimal treatment of amyloidosis, therefore, all patients should be treated in the context of a clinical trial when possible. Options include: · Bortezomibd /cyclophosphamide/dexamethasone · Bortezomibd ± dexamethasone · Bortezomibd /melphalan/dexamethasone Organ involvement based on · Cyclophosphamide/thalidomide/dexamethasone amyloidosis consensus criteriac · Dexamethasone/alpha-interferon · High-dose melphalane with stem cell transplant · Lenalidomide/cyclophosphamide/dexamethasone · Lenalidomide/dexamethasone