Optimizing Patient Outcomes in Non Hodgkin Lymphoma PowerPoint Presentation

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Optimizing Patient Outcomes in Non-Hodgkin Lymphoma: An Update for Oncology Nurses Barbara Barnes Rogers, CRNP, MN, AOCN, ANP-BC Adult Hematology-Oncology Nurse Practitioner Fox Chase Cancer Center

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Disclosure of Conflicts of Interest Barbara B. Rogers has an affiliation with Celgene (Advisory Board) and Allos, Cephalon, Seattle Genetics, and Millennium (Speaker’s Bureaus).

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Learning Objectives After completing this activity, the participant should be better able to: Discuss the classification, presentation, and diagnosis of NHL Explain the prognosis of NHL using established prognostic models Identify the different classes and mechanisms of therapeutic agents for treating NHL Recognize the signs and symptoms of side effects and complications associated with chemotherapy Manage chemotherapy side effects and complications in patients with NHL

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Non-Hodgkin Lymphoma A heterogeneous group of lymphoid tumors that have distinct clinical and biologic behaviors Accurate diagnosis of specific NHL subtype important to understand management Biological and clinical heterogeneity can be noted within each subtype

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Incidence of NHL Incidence rising: Faster than that of all other malignancies except lung cancer in women, melanoma and prostate cancer Age-adjusted incidence in US increased from 11.1 per 100,000 in 1975 to 19.8 per 100,000 in 2008 Reason for rising incidence: NHL in patients with acquired immunodeficiency syndrome (AIDS) Improvements in diagnosis Other reasons (most likely primary cause) Estimated new cases in the US in 2011 is 66,360 Race: 30% higher in whites than blacks Blacks > whites age less than 50 Whites > blacks age over 55 Greer J, Williams M. Wintrobe’s Clinical Hematology (12th Ed). Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins, 2009. American Cancer Society: Cancer facts and figures 2011.

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Epidemiology Variable world-wide distribution More common in males than females Represent ~10% of all childhood cancers in developed countries More common in adults than children Steady increase in incidence from childhood through age 80 years Seventh most common malignancy in US Represent 4% of all cancers

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Risk Factors Abnormality of immune function: HIV infection Iatrogenic immune suppression Autoimmune diseases Congenital immune deficiencies Wiskott-Aldrich X-linked lymphoproliferative disorder Infectious agents: Gamma herpes viruses Epstein-Barr virus - associated with African Burkitt lymphoma, AIDS-related DLBCL, NK/T-cell nasal type lymphoma Kaposi’s sarcoma-associated herpes virus (human herpes virus 8) - linked to primary effusion lymphomas and multicentric Castleman’s disease Human T-lymphotropic virus I (HTLVI) - adult T-cell leukemia/lymphoma Helicobacter pylori - gastric malt Hepatitis C virus - spenic marginal zone lymphoma; other B-cell lymphomas Campylobacter jejuni - immunoproliferative small intestinal disease Borrelia burgdorferi - primary cutaneous B-cell lymphoma Chlamydia psittaci - ocular adnexal lymphoma Greer J, Williams M. Wintrobe’s Clinical Hematology (12th Ed). Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins, 2009.

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Environmental Factors Associated with NHL Environmental and occupational exposures Organic compounds (organophosphate insecticides) Drug exposure Phenytoin Carbamazepine Methotrexate TNF-α inhibitors - etanercept, infliximab, adalimumab Toxic chemical exposure Greer J, Williams M. Wintrobe’s Clinical Hematology (12th Ed). Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins, 2009.

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Clinical Features of NHL Painless adenopathy - more common in cervical, axilla, or groin B symptoms - fevers, night sweats, weight loss Extranodal disease can be detected in up to 40% of patients GI tract most common site Skin CNS involvement Ocular Significant cytopenias rare Hepatosplenomegaly - common feature of advanced disease manifested by upper abdominal pain

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Where Do B-Cell Lymphomas Originate? Jaffe E, et al. Blood. 2008;112:4384-4399.

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Classifications of NHL B-cell vs T-cell B-cell NHL - 88% of all NHLs T-cell NHL - 12% of all NHLs Indolent vs Aggressive WHO classification includes: Immunophenotypic Molecular Genetic Clinical elements

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Diagnostic Work-Up

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Indications for Lumbar Puncture Small non-cleaved cell NHL Lymphoblastic lymphomas NHL of certain sites: Nasopharynx Epidural space Testes Large cell with marrow involvement HIV + Greer J, Williams M. Wintrobe’s Clinical Hematology (12th Ed). Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins, 2009.

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Subtypes of NHL MALT-type marginal-zone B cell (7.5%) Lichtman MA. Williams Hematology. (7th Ed). New York, NY: McGraw Hill, 2006;1408. Mantle cell (6%)

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Antigen Expression Associated with B-Cell NHL Bone Marrow Periphery (Spleen, Lymph Node) Pro-B Pre-B Immature B Mature B GC B Mature B Memory B Plasma Cell Activated B-cells Plasmablast WM MM ALL CLL, PLL Burkitt’s, FL, DLBCL, HCL ALL = acute lymphoblastic leukemia FL = follicular lymphoma HCL = hairy cell leukemia CLL = chronic lymphocytic leukemia DLBCL = diffuse large B-cell lymphoma MM = multiple myeloma PLL = prolymphocytic leukemia WM = Waldenström’s macroglobulinemia Jaffe ES, et al, eds. World Health Organization Classification of Tumours. 2001. Hale G, et al. Tissue Antigens. 1990;35:118-127. Freeman GJ, et al. J Immunol. 1989;143:2714-2722.

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Molecular Indices in Lymphocytic Malignancies Kurtin S. Oncology Nurse. 2008;1(5):1-2.

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Differences Between Childhood and Adult Non-Hodgkin Lymphomas Greer J, Williams M. Wintrobe’s Clinical Hematology (12th Ed). Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins, 2009.

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Indolent NHL Long median survival Slow but continuous decline in survival Usually advanced stage at presentation Respond to therapy but relapse May transform to aggressive lymphoma Rarely, can spontaneously regress

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Indolent Lymphoma Subtypes Follicular lymphoma Small lymphocytic lymphoma Lymphoplasmacytic lymphoma (Waldenström macroglobulinemia) Marginal zone lymphoma Splenic marginal zone lymphoma Primary cutaneous anaplastic large cell lymphoma Mycosis fungoides (Sézary syndrome) National Cancer Institute: Adult Non-Hodgkin Lymphoma Treatment (PDOR), cellular classification of adult NHL.

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Aggressive Lymphomas Present acutely or sub-acutely with: A rapidly growing mass Systemic B symptoms: Fever Night sweats Weight loss Elevated serum LDH (lactate dehydrogenase) Elevated uric acid Examples: Diffuse large B cell lymphoma Burkitt lymphoma Adult T cell leukemia/lymphoma Precursor B and T lymphoblastic leukemia/lymphoma Mantle cell lymphoma Greer J, Williams M. Wintrobe’s Clinical Hematology (12th Ed). Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins, 2009.

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Peripheral T-cell Lymphoma Subtypes O’Leary. Curr Opin Hematol. 2009;16:292. International T-Cell Lymphoma Project. J Clin Oncol. 2008;26:4124. de Leval. Hematology Am Soc Hematol Educ Program. 2008;272. ALCL = anaplastic large-cell lymphoma ALK = anaplastic lymphoma kinase PTCL = peripheral T-cell lymphoma.

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Ann Arbor Staging System

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Prognostic Indexes IPI = International Prognostic Index AA-IPI = Age Adjusted IPI FLIPI = Follicular Lymphoma IPI MIPI = Mantle Cell IPI PIT = Peripheral T cell NHL IPI The International Non-Hodgkin’s Lymphoma Prognostic Factor Project. N Engl Med. 1993;329:987-994. Solal-Celigny, et al. Blood. 2004;104:1258-1265. Gallamini A, et al. Blood. 2004;103:2474-2479. Geisler C, et al. Blood. 2010;115:1530-1533.

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Progression-Free Survival Based on IPI Sehn L, et al. Blood. 2007;109:1857-1861.

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Overall Survival of Patients with PTCL Based on Prognostic Index for PTCL (PIT) Group 1 - 0 risk factors Group 2 - 1 risk factor Group 3 - 2 risk factors Group 4 - 3-4 risk factors Gallamini A, et al. Blood. 2004;103:2474-2479.

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Treatment Related Issues Ability of patient to tolerate treatment dependent on: Age Performance status Immunodeficiency from pre-lymphomatous condition Higher mortality in elderly Increased treatment related toxicities Death from unrelated causes are increased Greater lymphoma related mortality

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Management of Indolent Lymphoma: Treatment Options Watchful waiting Local radiation for limited stage disease Chemotherapy: Alkylating agent Nucleoside analog Combination chemotherapy Immunotherapy: Unconjugated monoclonal antibody Radioimmunotherapy Interferons Interleukins Vaccines Combined modality therapy: Chemotherapy and radiation therapy Chemotherapy and immunotherapy Transplantation: Autologous Allogeneic: Myeloablative Non-myeloablative Selective therapies: Antibiotics in selected maltomas Splenectomy Greer J, Williams M. Wintrobe’s Clinical Hematology (12th Ed). Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins, 2009.

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Management of Diffuse Large B-Cell Lymphoma (DLBCL) Initial: R-CHOP =/- IFRT Management of aggressive (high Ki67) DLBCL Relapsed: +/- autologous transplant RICE R-DHAP R-ESHAP R-GemOx R-MINE R-GDP NCCN. Non-Hodgkin’s Lymphoma. Version 2.2012.

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NCCN. Non-Hodgkin’s Lymphoma. Version 2.2012.

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Foss F, et al. Blood. 2011;117:6756-6767.

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Role of Transplant in the Management of NHL Outcomes dependent on: Disease State: Type of lymphoma Remission status - best outcome in patients in first CR or have minimal disease before transplant Patients with disease that is responsive to therapy have 30-60% salvage rate Patients with resistant relapse have 0-15% salvage rate Patient factors: Age Performance Status Source of stem cells Autologous Allogeneic - higher mortality rate No superior preparative regimen

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Overall Survival in PTCL The International PTCL and NK/T-Cell Lymphoma Study ATLL = adult T-cell leukemia/lymphoma; OS = overall survival. International T-Cell Lymphoma Project, 2008. Vose J, et al. J Clin Oncol. 2008;26:4124-4130.

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Side Effects of Agents Used in the Treatment of B-Cell Lymphomas- CHOP Wilkes G, Barton-Burke M. Oncology Nursing Drug Handbook (2011 Ed). Sudbury, MA: Jones and Bartlett Publishers, 2011.

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Side Effects of Agents Used in the Management of NHL Wilkes G, Barton-Burke M. Oncology Nursing Drug Handbook (2011 Ed). Sudbury, MA: Jones and Bartlett Publishers, 2011.

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Side Effects of Agents Used in the Treatment of B-Cell Lymphomas-Radioimmunotherapy Wilkes G, Barton-Burke M. Oncology Nursing Drug Handbook (2011 Ed). Sudbury, MA: Jones and Bartlett Publishers, 2011.

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Side Effects of Agents Used in the Management of T-Cell NHL Wilkes G, Barton-Burke M. Oncology Nursing Drug Handbook (2011 Ed). Sudbury, MA: Jones and Bartlett Publishers, 2011.

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Wilkes G, Barton-Burke M. Oncology Nursing Drug Handbook (2011 Ed). Sudbury, MA: Jones and Bartlett Publishers, 2011. Management of Side Effects of Agents Used in the Management of NHL

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Management of Side Effects of Agents Used in the Management of NHL Wilkes G, Barton-Burke M. Oncology Nursing Drug Handbook (2011 Ed). Sudbury, MA: Jones and Bartlett Publishers, 2011.

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Wilkes G, Barton-Burke M. Oncology Nursing Drug Handbook (2011 Ed). Sudbury, MA: Jones and Bartlett Publishers, 2011. Management of Side Effects of Agents Used in the Management of NHL

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Management of NHL in the Elderly Over half of new cases occur in those over the age of 60 years Prognosis poor in the elderly Poor performance status Reduced vital organ reserve Comorbid diseases Biologic features of lymphoma

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Management of NHL in Pregnancy Lymphoma during pregnancy is rare (about 100 reported cases) Therapy is based on histologic type and the point of gestation at diagnosis Most women who develop NHL during pregnancy have aggressive histologies and advanced-stage disease Unusually high incidence of breast, ovarian, uterine and cervix involvement - most likely due to hormonal influenced and increased blood flow to these organs Placental involvement rare Transmission to fetus uncommon Staging studies are limited due to concerns about radiation exposure during pregnancy CXR can be done MRI can be used but to be avoided during first trimester Ultrasound and echocardiograms can be useful PET can be performed after delivery but since FDG is concentrated in breast tissue, patients should avoid breast feeding for 72 hours after the scan Prognosis for mother relatively poor: EFS 40-45% Due to aggressive nature of disease and advanced stage Brenner B, et al. Lancet. 2012;379:580-587.

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Management of NHL During Pregnancy Abortion should be considered when aggressive lymphoma is diagnosed during first trimester unless localized above diaphragm In that situation, can use involved field radiation therapy (with abdominal shielding) Radiation should be avoided until third trimester Combination chemotherapy can be given in second or third trimester Anthracyclines have been given without untoward effects to mother or fetus but should be avoided if possible Rituximab plus chemotherapy has been given without evidence of harm Early delivery should be considered: Avoid myelosuppression To initiate intensive chemotherapy Complete staging after delivery Low-grade lymphomas can be observed until after delivery Brenner B, et al. Lancet. 2012;379:580-587.

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Long-term Effect of Therapy Not as well defined as in HL Appear to be similar to HL and depend on: Therapy used Age of patient Comorbid illnesses Long-term effect: Endocrine - infertility, hypothyroid, panhypopituitarism, growth retardation Psychosocial issues Transfusion - induced viral infections Second neoplasms Radiation is main cause of endocrine and neurologic toxicities and secondary solitary neoplasms Cardiotoxicity from anthracyclines is manifested as CHF Cumulative incidence of cardiovascular disease in NHL treated with anthracycline was: 12% at 5 years 22% at 10 years

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Secondary Malignancies Increased risk over time for: AML Bladder cancer Kidney cancer Lung cancer Malignant melanoma HL Up to 10% of patients with NHL treated with chemotherapy or autologous transplant may develop MDS or AML within 10 years of their initial therapy Greer J, Williams M. Wintrobe’s Clinical Hematology (12th Ed). Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins, 2009.

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Key Takeaways NHL is a heterogeneous group of malignancies that have distinct morphologic and molecular differences The distinct subtypes of NHL require specific management There are multiple prognostic indexes that can be used to calculate the level of risk of the patient’s lymphoma The prognosis is poorer in the elderly diagnosed with NHL than in younger patients Nursing interventions can assist patients in managing side effects from their treatment