waldenstroms

Version 2.2011, 09/17/10 © National Comprehensive Cancer Network, Inc. 2010, 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 Index WM/LPL Table of Contents Discussion Continue NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines™) Waldenstrom’s Macroglobulinemia / Lymphoplasmacytic Lymphoma Version 2.2011 NCCN.org ¨ Version 2.2011, 09/17/10 © National Comprehensive Cancer Network, Inc. 2010, 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 Index WM/LPL Table of Contents Discussion * 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 Hospital 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 NCCN Guidelines Panel Disclosures 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 Steven P. Treon, MD, PhD Guido Tricot, MD, PhD ‡ Huntsman Cancer Institute at the University of Utah 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 † Dana-Farber/Brigham and Women's Cancer Center | Massachusetts General Hospital Edward A. Faber, Jr., DO UNMC Eppley Cancer Center at The Nebraska Medical Center Carol Ann Huff, MD † The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Adetola Kassim, MD ‡ Vanderbilt-Ingram Cancer Center Gwynn Long, MD Duke Comprehensive 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 � NCCN Guidelines™ Version 2.2011 Panel Members Waldenstrom’s Macroglobulinemia/ Lymphoplasmacytic Lymphoma NCCN Dorothy A. Shead, MS Rashmi Kumar, PhD * ¨ Printed by wei ou on 10/10/2010 2:03:48 AM. For personal use only. Not approved for distribution. Copyright © 2010 National Comprehensive Cancer Network, Inc., All Rights Reserved. Version 2.2011, 09/17/10 © National Comprehensive Cancer Network, Inc. 2010, 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 Index WM/LPL Table of Contents Discussion 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 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 be reproduced in any form without the express written permission of NCCN. ©2010. NCCN Guidelines™ Version 2.2011 Table of Contents Waldenstrom’s Macroglobulinemia/ Lymphoplasmacytic Lymphoma ¨ Panel Members Updates Diagnosis, Workup, Indications for Treatment (WMLPL-1) Primary Treatment, Relapse (WMLPL-2) WHO Criteria for Lymphoplasmacytic Lymphoma and Waldenstr ms Macroglobulinemia International Workshop Criteria (WMLPL-A) Suggested Treatment Regimens (WMLPL-B) Suggested References (WMLPL-C) Waldenstroms Macroglobulinemia o ¨ ¨ Printed by wei ou on 10/10/2010 2:03:48 AM. For personal use only. Not approved for distribution. Copyright © 2010 National Comprehensive Cancer Network, Inc., All Rights Reserved. Version 2.2011, 09/17/10 © National Comprehensive Cancer Network, Inc. 2010, 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 Index WM/LPL Table of Contents Discussion 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. UPDATES Updates in version 1.2011 NCCN Guidelines include: Waldenstroms Macroglobulinemia was originally included in the NCCN Multiple Myeloma Guidelines, it has been completely updated and reformatted as an additional Guideline to the NCCN Library of Clinical Practice Guidelines in Oncology. The name has been changed to Waldenstrom’s Macroglobulinemia/Lymphoplasmacytic Lymphoma Added a new diagnostic section. Hematopathology review of all slides with at least one paraffin block representative of the tumor. Rebiopsy if consult material is nondiagnostic. Adequate immunophenotyping to establish diagnosis Typical immunophenotype: CD19+, CD20+, sIgM+; CD5, CD10, CD23 may be positive in 10-20% of cases and does not exclude diagnosis The Workup section has been expanded to include essential tests and those that are considered useful in certain circumstances such as: Neurology consult Anti-MAG antibodies/anti-GM1 Electromyelogram Fat pad biopsy and/or congo red staining of bone marrow for amyloid Retinal exam (if IgM 3.0 gm/dL) A new page which includes the WHO Criteria for Lymphoplasmacytic Lymphoma and Waldenstrom’s Macroglobulinemia and International Workshop Criteria. A new page that lists suggested treatment regimens for primary therapy and salvage therapy. A new page of suggested reading. Waldenstrom’s Macroglobulinemia/Lymphoplasmacytic Lymphoma Waldenstrom’s Macroglobulinemia � � � � � � � � � � � � � � General: WMLPL-1 WMLPL-A WMLPL-B WMLPL-C NCCN Guidelines™ Version 2.2011 Updates Waldenstrom’s Macroglobulinemia/ Lymphoplasmacytic Lymphoma ¨ ¨ ¨ ¨ ¨ Updates in version 2.2011 NCCN Waldenstrom’s Macroglobulinemia/Lymphoplasmacytic Lymphoma Guidelines include: � The Discussion section has been updated to correspond with the revised algorithm. Discussion ¨ ¨ Printed by wei ou on 10/10/2010 2:03:48 AM. For personal use only. Not approved for distribution. Copyright © 2010 National Comprehensive Cancer Network, Inc., All Rights Reserved. Version 2.2011, 09/17/10 © National Comprehensive Cancer Network, Inc. 2010, 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 Index WM/LPL Table of Contents Discussion 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. See Primary Treatment (WMLPL-2) WMLPL-1 WORKUP Symptoms related to: � � � � � � � � Hyperviscosity Neuropathy Organomegaly Amyloidosis Cold agglutinin disease Cryoglobulinemia Cytopenias associated with disease Bulky adenopathy Essentiala � � Hematopathology review of all slides with at least one paraffin block representative of the tumor. Rebiopsy if consult material is nondiagnostic. Adequate immunophenotyping to establish diagnosis Typical immunophenotype: CD19+, CD20+, sIgM+; CD5, CD10, CD23 may be positive in 10-20% of cases and does not exclude diagnosis � DIAGNOSIS Essential Useful in certain circumstances � � � � � � � � � � � � � � � � � � � H&P CBC Comprehensive panel Quantitative immunoglobulins/Immunofixation Serum protein electrophoresis (SPEP) Beta-2 microglobulin Serum vicosity Unilateral aspirate and biopsy Hepatitis C testing Hepatitis B testing, if rituximab planned Cryocrit Cold agglutinins Neurology consult Anti-MAG antibodies/anti-GM1 Electromyelogram Fat pad biopsy and/or congo red staining of bone marrow for amyloid Retinal exam (if IgM 3.0 gm/dL) differential, platelets Chest/abdominal/pelvic CT b c c,d e e e e INDICATIONS FOR TREATMENT a c e . Most patients with serum viscosity of less than 4 cP will not have symptoms of hyperviscosity. Consider in patients with suspected cryoglobulinemia. If cryocrit positive, then repeat testing of initial serum IgM, and obtain all subsequent serum IgM levels under warm conditions. In patients presenting with suspected disease related peripheral neuropathy. b d See WHO Criteria for Lymphoplasmacytic Lymphoma and Waldenström’s Macroglobulinemia (WMLPL-A) NCCN Guidelines™ Version 2.2011 Waldenstrom’s Macroglobulinemia/ Lymphoplasmacytic Lymphoma ¨ Printed by wei ou on 10/10/2010 2:03:48 AM. For personal use only. Not approved for distribution. Copyright © 2010 National Comprehensive Cancer Network, Inc., All Rights Reserved. Version 2.2011, 09/17/10 © National Comprehensive Cancer Network, Inc. 2010, 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 Index WM/LPL Table of Contents Discussion 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. WMLPL-2 Plasmapheresis for symptomatic hyperviscosity and or or Clinical Trial f Primary therapy: � � Combination therapy Single agent (such as rituximab) g f,g PRIMARY TREATMENT Complete response No response/ Progressive disease Partial response Observe until progressive disease or Consider rituximab for maintenance therapy Asymptomatic: Observe until progressive disease or Consider rituximab for maintenance therapy Choose alternative therapyg If transformation, see NCCN for Non- Hodgkin’s Lymphoma’s, Follicular Lymphoma Guidelines � 12 mo Choose alternative therapyg < 12 mo RELAPSE f g Plasmapheresis should be performed for patients with symptomatic hyperviscosity, and before treatment with rituximab containing regimen in patients with IgM 5000 mg/dL. IgM should be monitored closely in these patients thereafter and plasmapheresis considered again if symptomatic hyperviscosity occurs or if IgM . � � 5000 mg/dL while on rituximab containing therapy. See Suggested Treatment Regimens (WMLPL-B) If persistent symptoms May use previous treatment or consider alternative therapyg Waldenstrom’s Macroglobulinemia/ Lymphoplasmacytic Lymphoma ¨ NCCN Guidelines™ Version 2.2011 Waldenstrom’s Macroglobulinemia/ Lymphoplasmacytic Lymphoma ¨ Printed by wei ou on 10/10/2010 2:03:48 AM. For personal use only. Not approved for distribution. Copyright © 2010 National Comprehensive Cancer Network, Inc., All Rights Reserved. Version 2.2011, 09/17/10 © National Comprehensive Cancer Network, Inc. 2010, 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 Index WM/LPL Table of Contents Discussion 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. WMLPL-A Proposed Criteria for the Diagnosis of Waldenström’s Macroglobulinemia � � � � IgM monoclonal gammopathy of any concentration Bone marrow infiltration by small lymphocytes, plasmacytoid cells, and plasma cells Diffuse, interstitial, or nodular pattern of bone marrow infiltration CD19+, CD20+, sIgM+;CD5, CD10, CD23 can be expressed in some cases of and does not exclude diagnosis. Waldenström’s Macroglobulinemia Reprinted .with permission from Elsevier. Owen RG. Developing diagnostic criteria in Waldenstrom's macroglobulinemia. Semin Oncol. 2003;30:196-200 � � Lymphoplamacytic lymphoma: Waldenström’s Macroglobulinemia: � � � � Neoplasm of small B lymohocytes, plasmacytoid lymphocytes, and plasma cells Usually involving bone marrow and sometimes lymph nodes and spleen Does not fulfill criteria of any other small B-cell lymphoid neoplasm that may also have plasmacytic differentiation Lymphoplasmacytic lymphoma with bone marrow involvement and IgM monoclonal gammopathy of any concentration From Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW (Eds): World Health Organization Classification of Tumours of the Haematopoietic and Lymphoid Tissues. IARC Press: Lyon 2008. WALDENSTRÖM’S MACROGLOBULINEMIA INTERNATIONAL WORKSHOP CRITERIA WHO CRITERIA FOR AND WLYMPHOPLASMACYTIC LYMPHOMA ALDENSTRÖM’S MACROGLOBULINEMIA NCCN Guidelines™ Version 2.2011 Waldenstrom’s Macroglobulinemia/ Lymphoplasmacytic Lymphoma ¨ Printed by wei ou on 10/10/2010 2:03:48 AM. For personal use only. Not approved for distribution. Copyright © 2010 National Comprehensive Cancer Network, Inc., All Rights Reserved. Version 2.2011, 09/17/10 © National Comprehensive Cancer Network, Inc. 2010, 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 Index WM/LPL Table of Contents Discussion 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. Primary Therapy: Non-stem cell toxic Possible stem cell toxicity and/or risk of transformation (or unknown) � � � � � � Bortezomib ± rituximab Bortezomib, dexamethasone, rituximab Cladribine ± rituximab Chlorambucil 1,2,3 1,2,3 1 1,4,5 4,5 � � � � Rituximab Rituximab/cyclophosphamide/prednisone Rituximab/cyclophosphamide/dexamethasone Thalidomide ± rituximab Bendamustine ± rituximab Fludarabine ± rituximab 1 1 1 1 1,4,5 SUGGESTED TREATMENT REGIMENS 1 2 4 5 6 In patients with symptomatic hyperviscosity plasmapheresis should first be performed; plasmapheresis should also be considered before treatment with rituximab for asymptomatic patients with an IgM 5,000 mg/dL to avoid aggravation of serum viscosity on the basis of rituximab related IgM flare. Rituximab may also be held in patients with elevated serum IgM levels for initial treatment cycles. Consider particularly for patients presenting with symptomatic hyperviscosity, or in whom rapid IgM reduction is required. May be associated with disease transformation and/or development of MDS/AML in patients. Avoid in patients who are potential autologous stem cell transplant candidates. Should ideally be undertaken in the context of a clinical trial. Waldenström’s Macroglobulinemia Consider herpes zoster prophylaxis for patients treated with bortezomib. Waldenström’s Macroglobulinemia � 3 Salvage Therapy: Non-stem cell toxic Possible stem cell toxicity and/or risk of transformation (or unknown) Stem cell transplant � � � � � � � � � � Alemtuzumab Bortezomib ± rituximab Bortezomib, dexamethasone, rituximab Cladribine ± rituximab Chlorambucil 1,2,3 1,2,3 1 1,4,5 4,5 � � � Everolimus Rituximab Rituximab/cyclophosphamide/prednisone Rituximab/cyclophosphamide/dexamethasone Thalidomide ± rituximab Bendamustine ± rituximab Fludarabine ± rituximab In selected cases stem cell transplantation may be appropriate with either: High dose therapy with stem cell rescue Allogeneic stem cell transplant (ablative or non-ablative) 1 1 1 1 1,4,5 6 � � WMLPL-B NCCN Guidelines™ Version 2.2011 Waldenstrom’s Macroglobulinemia/ Lymphoplasmacytic Lymphoma ¨ Printed by wei ou on 10/10/2010 2:03:48 AM. For personal use only. Not approved for distribution. Copyright © 2010 National Comprehensive Cancer Network, Inc., All Rights Reserved. Version 2.2011, 09/17/10 © National Comprehensive Cancer Network, Inc. 2010, 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 Index WM/LPL Table of Contents Discussion 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. SUGGESTED REFERENCES � � � � � � � � � Cheson BD, Rummel MJ. Bendamustine: rebirth of an old drug. J Clin Oncol. 2009;27:1492-1501. Dimopoulos MA, Anagnostopoulos A, Kyrtsonis MC, et al. Primary treatment of Waldenstrom macroglobulinemia with dexamethasone, rituximab, and cyclophosphamide. J Clin Oncol. 2007;25:3344-3349. Dimopoulos MA, Anagnostopoulos A, Zervas C, et al. Predictive factors for response to rituximab in Waldenstrom's macroglobulinemia. Clin Lymphoma. 2005;5:270-272. Dimopoulos MA, Gertz MA, Kastritis E, et al. Update on treatment recommendations from the Fourth International Workshop on Waldenstrom's Macroglobulinemia. J Clin Oncol. 2009;27:120-126. Dimopoulos MA, Zervas C, Zomas A, et al. Treatment of Waldenstrom's macroglobulinemia with rituximab. J Clin Oncol. 2002;20:2327-2333. Gertz MA, Rue M, Blood E, Kaminer LS, Vesole DH, Greipp PR. Multicenter phase 2 trial of rituximab for Waldenstrom macroglobulinemia (WM): an Eastern Cooperative Oncology Group Study (E3A98). Leuk Lymphoma. 2004;45:2047-2055. Ghobrial IM, Gertz M, Laplant B, et al. Phase II trial of the oral mammalian target of rapamycin inhibitor everolimus in relapsed or refractory Waldenstrom macroglobulinemia. J Clin Oncol. 2010;28:1408-1414. Ghobrial IM, Hong F, Padmanabhan S, et al. Phase II trial of weekly bortezomib in combination with rituximab in relapsed or relapsed and refractory Waldenstrom macroglobulinemia. J Clin Oncol. 2010;28:1422- 1428. Hunter ZR, Branagan AR, Manning R, et al. CD5, CD10, and CD23 expression in Waldenstrom's macroglobulinemia. Clin Lymphoma. 2005;5:246-249. � � � � � � � Ioakimidis L, Patterson CJ, Hunter ZR, et al. Comparative outcomes following CP-R, CVP-R, and CHOP-R in Waldenstrom's macroglobulinemia. Clin Lymphoma Myeloma. 2009;9:62-66. Leleu X, Soumerai J, Roccaro A, et al. I