Non-Hodgkin s Lymphomas Version

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1 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ) n-hodgkin s Lymphomas Version NCCN.g Continue Version , 03/03/15 National Comprehensive Cancer Netwk, Inc. 2015, All rights reserved. The NCCN Guidelines and this illustration may not be reproduced in any fm without the express written permission of NCCN.

2 Castleman's Disease

3 DIAGNOSIS a,b,c WORKUP f ESSENTIAL: Physical exam: attention to node-bearing areas, including ESSENTIAL: Waldeyer s ring, and to size of liver and spleen Hematopathology review of all slides with at Perfmance status least one paraffin block representative of the Assess f criteria f active diseaseg lymphoproliferative disder. Rebiopsy if CBC, differential, platelets consult material is nondiagnostic. Comprehensive metabolic panel An FNA ce needle biopsy alone is not LDH, CRP, ESR generally suitable f initial diagnosis of Beta-2-microglobulin, serum protein electrophesis and See Unicentric Castleman s disease. Excisional incisional urine electrophesis with immunofixation, serum light CD-2 biopsy are preferable. chains, quantitative immunoglobulins HIV ELISA, HHV-8 DNA titer by PCR, Hepatitis B testing, h Adequate immunophenotyping to establish EBV DNA titer by PCR diagnosisd PET-CT scan (preferred) chest/abdominal/pelvic CT IHC panel: kappa/lambda, CD20, CD3, CD5, with contrast of diagnostic quality CD138, HHV-8 LANA-1 Pregnancy testing in women of child-bearing age (if EBER-ISH chemotherapy planned) USEFUL UNDER CERTAIN CIRCUMSTANCES USEFUL UNDER CERTAIN CIRCUMSTANCES: If HHV-8/KSHV HIV positive, screening f concurrent See Molecular analysis ( PCR) to detect Kaposi's sarcoma is strongly recommended Multicentric CD-3 immunoglobulin and TCR gene rearragements Bone marrow biopsy + aspirate IHC: Ki-67 index; Ig heavy chains, e CD10, BCL2, Neck CT with contrast BCL6, cyclin D1, CD21, CD23, CD38, MUM-1, MUGA scan/echocardiogram if anthracycline PAX-5 anthracenedione-based regimen is indicated sil-6, sil10, VEGF, uric acid, ferritini Cell surface marker analysis by flow cytometry: kappa/lambda, CD19, CD20, CD5, CD23, CD10 Hepatitis C testing of fertility issues and sperm banking af AIDS-related Lymphoma associated with Castleman s disease, e In plasma cell variant HHV8+, plasmablasts are IgM lambda while nmal plasma cells are IgG A polytypic. see AIDS-1. F DLBCL-associated with CD in non-hiv patients, f see BCEL-1. If concurrent polyneuropathy and monoclonal plasma cell disder, a wkup f POEMS syndrome is recommended. bthere are 2 variants hyaline vascular (virtually always unicentric, gsee Criteria f Active Disease (CD-A). HHV8-) and plasma cell (may be multicentric, often HHV8+, +/- HIV+). h c Hepatitis B testing is indicated because of the risk of reactivation with immunotherapy + Two types of DLBCL are associated with the HHV8+ PC type: chemotherapy. Tests include hepatitis B surface antigen and ce antibody f a patient with plasmablastic (EBV-) and germinotropic (EBV+). no risk facts. F patients with risk facts previous histy of hepatitis B, add e- dsee Use of Immunophenotyping/Genetic Testing in Differential Diagnosis antigen. If positive, check viral load and consult with gastroenterologist. of Mature B-Cell and NK/T-Cell Neoplasms (NHODG-A). imeasurement of acute phase reactants maybe helpful in moniting therapy. te: All recommendations are categy 2A unless otherwise indicated. Version , 03/03/15 National Comprehensive Cancer Netwk, Inc. 2015, All rights reserved. The NCCN Guidelines and this illustration may not be reproduced in any fm without the express written permission of NCCN. CD-1

4 PRIMARY TREATMENT SECOND-LINE THERAPY Complete resection Recurrence resectable Unicentric CD Partial resection Asymptomatic Symptomatic See unresectable below Recurrence unresectable Radiation therapy Rituximab ± prednisone ± cyclophosphamide Consider embolization j resectable unresectable Complete resection Primary treatment option not previously given Relapsed/ refracty j Patients with non-bulky disease may be observed after RT. k Encourage biopsy to rule out transfmation to DLBCL concomitant development of other malignancies opptunistic infections. Consider local therapy with surgery RT embolization if amenable Systemic therapy with Rituximab ± prednisone ± cyclophosphamide Siltuximab/tocilizumab applies to HIV(-)HHV-8(-) patients te: All recommendations are categy 2A unless otherwise indicated. Version , 03/03/15 National Comprehensive Cancer Netwk, Inc. 2015, All rights reserved. The NCCN Guidelines and this illustration may not be reproduced in any fm without the express written permission of NCCN. CD-2

5 MCD (Criteria f active diseaseg present but no gan failure) HIV-1(-) HHV-8 (-) HIV-1(+)/HHV-8(+) i HIV-1(-)/HHV-8(+) PRIMARY TREATMENT Siltuximab Rituximab ± prednisone m Rituximab (preferred) ± liposomal doxubicinn ± prednisonem Zidovudine + ganciclovir/ valganciclovir If siltuximab, continue until progression If rituximab, observe and retreat at progression RELAPSED DISEASE Relapsed Relapsed Treat with alternate primary treatment befe moving onto treatment f refracty disease o Treat with alternate primary treatment befe moving onto treatment f refracty disease o Refracty Progressive Disease (CD-4) MCD (Fulminant HHV(+) ± gan failure) g See Criteria f Active Disease (CD-A). k l Combination therapy ± rituximab CHOP CVAD CVP Liposomal doxubicin Encourage biopsy to rule out transfmation to DLBCL concomitant development of other malignancies opptunistic infections. All HIV+ patients should be on combination antiretroviral therapy (cart). Relapsed m Concurrent Kaposi sarcoma therapy is required when rituximab prednisone is given f primary treatment. n Combination of rituximab and liposomal doxubicin is strongly recommended f patients with Kaposi sarcoma to avoid flare-up. o Rituximab ± prednisone may repeat without limit if progression 6 months of completion of rituximab. te: All recommendations are categy 2A unless otherwise indicated. Version , 03/03/15 National Comprehensive Cancer Netwk, Inc. 2015, All rights reserved. The NCCN Guidelines and this illustration may not be reproduced in any fm without the express written permission of NCCN. CD-3

6 REFRACTORY OR PROGRESSIVE DISEASE Refracty progressive disease Single-agent therapy (preferred) ± ganciclovir/valganciclovir if HHV-8(+) Etoposide [al IV] Vinblastine Liposomal doxubicin Combination therapy ± rituximab if not previously given CHOP CVAD CVP Liposomal doxubicin p Treat with alternate combination therapy ± rituximab not previously given Maintenance valganciclovir if HHV-8(+) Relapsed/ refracty Relapsed/ Refracty Consider alternative single agent combination therapy Btezomib ± rituximab Tocilizumab Anakinra Thalidomide ± rituximab Lenalidomide High-dose zidovudine + valganciclovir Autologous hematopoietic stem cell transplant p Single agent therapy is preferred f asymptomatic patients with no gan failure; combination therapy is preferred f patients with fulminant disease and gan failure. gsee Criteria f Active Disease (CD-A). kencourage biopsy to rule out transfmation to DLBCL concomitant development of other malignancies opptunistic infections. te: All recommendations are categy 2A unless otherwise indicated. Version , 03/03/15 National Comprehensive Cancer Netwk, Inc. 2015, All rights reserved. The NCCN Guidelines and this illustration may not be reproduced in any fm without the express written permission of NCCN. CD-4

7 CRITERIA FOR ACTIVE DISEASE a Fever Increased serum C-reactive protein level >20 mg/l in the absence of any other etiology At least three of the following other MCD-related symptoms Peripheral lymphadenopathy Enlarged spleen Edema Pleural effusion Ascitis Cough Nasal obstruction Xerostomia Rash Central neurologic symptoms Jaundice Autoimmune hemolytic anemia a Gérard L, Bérezné A, Galicier L, et al. Prospective study of rituximab in chemotherapy-dependent human immunodeficiency virus associated multicentric Castleman's disease: ANRS 117 CastlemaB Trial. J Clin Oncol 2007;25: te: All recommendations are categy 2A unless otherwise indicated. Version , 03/03/15 National Comprehensive Cancer Netwk, Inc. 2015, All rights reserved. The NCCN Guidelines and this illustration may not be reproduced in any fm without the express written permission of NCCN. CD-A