lymphoma and its treatment and nursing management.pptx

lymphoma

1. The lime green ribbon cancer milestones and the management guidelines

2. Outline Hodgkin Lymphoma Definition Epidemiology Risk factors Signs & Symptoms Diagnosis Classification Treatment Non- Hodgkin Lymphoma Overview Epidemiology Etiology Classification Follicular Lymphoma DLBCL Burkett lymphoma Cutaneous cell lymphoma Peripheral T cell lymphoma

3. L ymphoma Lymphoma is a broad term for cancer that begins in cells of the lymph system . The two main types are: 1- Hodgkin lymphoma 2- Non-Hodgkin lymphoma (NHL).

4. L ymphoma

5. Hodgkin Lymphoma(HL)

6. Hodgkin Lymphoma(HL) HL most frequently presents in lymph node groups above the diaphragm and/or in mediastinal lymph nodes .

7. Epidemiology Uncommon malignancy in adults. Estimated new cases and deaths from HL in the United States in 2019 : New cases: 8,110. Deaths: 1,000 .

8. Risk Factors Early adulthood (aged 20–39 years) (most often) or late adulthood (aged 65 years and older) (less often). Male Gender. Having a previous infection with the Epstein-Barr virus in the teenage years or early childhood. Having a first-degree relative with HL.

9. Signs and Symptoms These and other signs and symptoms may be caused by adult HL or by other conditions Painless, swollen lymph nodes in the neck, axilla, or inguinal area. Fever Night sweats. Unexplained Weight loss of 10% or more of baseline weight in the previous 6 months. Pruritus, especially after bathing Fatigue.

10. Diagnosis Diagnostic evaluation of patients with lymphoma may include the following: Biopsy (preferably excisional). History. Physical examination. Laboratory tests Radiographic examination HIV testing. Hepatitis B and C serology.

11. Hodgkin Lymphoma The goal of treatment = CURE FOR ALL P A TIEN T S .

12. Hodgkin Lymphoma Two main types of HL 1. Classical HL (CHL) – characterized by the presence of Reed‐Sternberg cells —CHL is divided into 4 subtypes: Nodular sclerosis—most common subtype (overall) Mixed cellularity—most common in HIV (+) patients Lymphocyte depleted—least common subtype Lymphocyte rich 2. Nodular lymphocyte‐predominant HL (NLPHL) —Lacks Reed‐Sternberg cells —Cells express CD20(+)

13. Hodgkin Lymphoma Classical HL (CHL)

14. Treatment of CHL Newly diagnosed patients with CHL treated according to the following categories Stage IA & IIA favorable Stage I & II unfavorable, non‐bulky disease Stage I & II unfavorable, bulky disease Stage III & IV

15. Favorable and Unfavorable disease NCCN unfavorable risk factors: Bulky mediastinal or >10 cm disease B symptoms ESR ≥50 OR ESR ≥30 with B symptoms >3 nodal sites of disease.

16. B Symptoms All stages of adult HL can be subclassified into A and B categories: “B for those with defined general symptoms (described below) and A for those without B symptoms.”  The B symptoms Unexplained weight loss (more than 10% of body weight in the 6 months before diagnosis). Unexplained fever with temperatures above 38°C. Drenching and recurrent night sweats. The most-significant B symptoms are fevers and weight loss.

17. Treatment Overview of CHL Treatment duration dependent upon stage and size – Stage IA & IIA favorable —ABVD x 2 cycles + 20 Gy involved site radiotherapy (ISRT) – Stage I & II unfavorable, non‐bulky disease —ABVD x 4 – 6 cycles ± ISRT — ABVD alone or alternating with MOPP.

18. Treatment Overview of CHL – Stage I & II unfavorable, bulky disease —ABVD x 4 – 6 cycles + 30 Gy ISRT –Chemotherapy alone is not recommended The difference between stage I & II bulky versus non‐bulky is that in the non‐bulky group, patients can receive chemotherapy alone if PET scan is negative – Stage III & IV —ABVD x 6 cycles ± ISRT

19. Protocols ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) Stanford V (doxorubicin, vinblastine, mechlorethamine, etoposide, vincristine, bleomycin, and prednisone) Escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone)

20. ABVD Regimen DOXOrubicin 25 mg /m² IV Days 1 & 15 Bleomycin 10 units /m² IV Days 1 & 15 VinBLAStine 6 mg /m² IV Days 1 & 15 Dacarbazine 375 mg /m² IV Days 1 & 15 Repeated every 28 days

21. Extravasations Anthracycline extravasations are most severe Apply cold or warm compresses – Cold for anthracyclines Dexrazoxane is indicated

22. Relapsed/Refractory CHL Treatment goal = CURE Relapsed disease is broken down into the following categories: Second line chemotherapy + autologous HSCT Second line chemotherapy only (HSCT contraindicated)

23. Relapsed/Refractory CHL Chemotherapy regimens include any of the following, as none have emerged as preferred regimens Brentuximab vedotin alone or in combination with the second-line regimens below DHAP (dexamethasone, cisplatin, high-dose cytarabine) ESHAP (etoposide, methylprednisolone, high-dose cytarabine, cisplatin) Gemcitabine/bendamustine/vinorelbine GVD (gemcitabine, vinorelbine, liposomal doxorubicin) ICE (ifosfamide, carboplatin, etoposide) IGEV (ifosfamide, gemcitabine, vinorelbine) Bendamustine - Single agent therapy

24. Relapsed CHL Brentuximab Vedotin (Adcetris ®)

25. Administration DO NOT administer as an IV push or bolus. Reconstitute each 50 mg vial with 10.5 mL of SWFI to yield a single-use 5 mg/mL solution. Gently swirl the vial to aid dissolution; do not shake after reconstitution Add to an infusion bag containing at least 100ml volume to achieve a final concentration of 0.4- 1.8 mg/mL and use within 24 hours. Can be diluted into normal saline, 5% dextrose or lactated ringer's injection. Infuse IV over 30 min.

26. I n t e r actions CYP3A4 inducers ● CYP3A4 inhibitors CYP3A4 inducers (i.e. phenytoin, rifampin, dexamethasone, carbamazepine,phenobarbital, St. ↓ exposure to MMAE (up to 46%) ↑ metabolism of MMAE Caution; monitor for efficacy CYP3A4 inhibitors (i.e. ketoconazole, clarithromycin, ritonavir, fruit or juice from grapefruit, Seville oranges or starfruit)

27. Hodgkin Lymphoma Nodular Lymphocyte‐Predominant HD (NLPHD)

28. Nodular Lymphocyte‐Predominant HD No preferred chemotherapy regimen exists ABVD is often used based on data with CHL Consistently express the CD20 antigen ‐ Rituximab can be considered as single‐agent therapy or in combination with multidrug chemotherapy regimens

29. Non-Hodgkin lymphomas (NHLs)

30. Non-Hodgkin lymphomas (NHLs) Tumors originating from lymphoid tissues, mainly of lymph nodes. (originating in B-lymphocytes , T-lymphocytes or natural killer cells (NK))

31. Epidemiology Incidence NHL occurs with increasing frequency, with about 60.000 new cases annually in the United States. According guidelin e s estimated t o T h e NCCN In 2 01 9 , an 74,200 peopl e will be diagnosed with NHL and will be approximately 19,790 deaths due to the disease.

32. E tiology Pathogens (Infections). Immunodeficiency or immune dysregulation. Treatment related. Environmental factors (Toxins). genetics (Chromosomal translocations).

33. WHO / Revised European American Lymphoma ( REAL) Classification B-cell lymphomas( 80% - 85%) T-cell lymphomas (15% - 20%) Diffuse large B-cell lymphoma Follicular lymphoma Chronic lymphocytic leukemia /small lymphocytic lymphoma Mantle cell lymphoma Marginal zone B-cell lymphomas Burkitt lymphoma Lymphoplasmacytic lymphoma (Waldenstrom macroglobulinemia) Hairy cell leukemia Primary central nervous system (CNS) lymphoma Precursor T-lymphoblastic lymphoma/leukemia Peripheral T-cell lymphomas Cutaneous T-cell lymphomas (mycosis fungoides, Sezary syndrome, and others) Adult T-cell leukemia/lymphoma Angioimmunoblastic T-cell lymphoma Extranodal natural killer/T-cell lymphoma, nasal type Enteropathy-associated intestinal T-cell lymphoma (EATL) Anaplastic large cell lymphoma (ALCL) Peripheral T-cell lymphoma, unspecified

34. Non-Hodgkin lymphomas (NHLs) Common subtypes of B-cell non-Hodgkin lymphoma according to NCCN Guidelines and WHO criteria Subtype Indolent Follicular lymphoma Marginal zone B-cell lymphomas Aggressive Mantle cell lymphoma Diffuse large B-cell lymphoma primary mediastinal large B-cell lymphoma 4- Gray zone lymphoma Very aggressive Burkitt lymphoma Burkitt like lymphoma

35. Non-Hodgkin lymphomas (NHLs) Common subtypes of T-cell non-Hodgkin lymphoma according to NCCN Guidelines and WHO criteria Subtype Indolent Cutenous T-cell lymphoma (CTCL) Aggressive Peripheral T-cell lymphomas (PTCL) Extranodal natural killer/T-cell lymphoma

36. The treatment of non-Hodgkin lymphoma (NHL) varies greatly, depending on the following factors Tumor stage Phenotype (B-cell, T-cell or natural killer (NK) cell/null-cell) Histology (i.e: low, intermediate, or high-grade) Symptoms Performance status (PS) Patient age Comorbidities

37. B-Cell NHL A. Indolent I. Follicular Lymphoma

38. Indolent or Low‐grade NHL: FL The most common indolent NHL & the second most common NHL Accounts for ~22% of all newly diagnosed cases Median age of diagnosis: 60 years old Goal of therapy = palliation Few patients achieve cure with therapy regardless of stage Many patients go years without needing treatment

39. Indolent or Low‐grade NHL: FL Indications for treatment Autoimmune cytopenia, recurrent infections, symptomatic disease, threatened end organ function, cytopenia, bulky disease, steady progression over 6 months or patient preference

40. Stage I & II, non‐bulky (Grade 1 – 2) Radiotherapy preferred Watch and wait may be appropriate in selected cases. When patient has indications for treatment (in order of preference): BR (Category 1) R-CHOP (Category 1) R-CVP (Category 1) Rituximab x 4 weekly doses

41. Treatment Protocols BR q28days x 6 cycles B = bendamustine 90 mg/m² IV D1 and 2 R = rituximab 375 mg/m² IV D1 R-CHOP (Rituximab -cyclophosphamide, doxorubicin, vincristine, and prednisone) R-CVP q21days x 6 cycles R = rituximab 375 mg/m² IV D1 C = cyclophosphamide 750 mg/m2 IV D1 V = vincristine 1.4 mg/m² IV D1 P = prednisone 100 mg PO D1-5

42. Rituximab

43. P r epa r a tion Rituximab (IV) Dilute to a final concentration of 1-4 mg/mL in normal saline or D5W . To avoid foaming, gently invert the bag to mix the solution. Do not admix with other drugs. Administer rituximab through a dedicated line. Keep vials refrigerated; do not freeze. Protect from light.

44. Administration ). Infusion rates: Consider a slower infusion rate or split dosing where bulky disease present or WBC > 25 x 10⁹/L. First infusion: Initial rate of 50 mg/h, then escalate rate in 50 mg/h increments every 30 minutes, to a maximum of 400 mg/h (about 4.25 hours in total). Subsequent infusions: Initial rate of 100 mg/h, then escalate rate in 100 mg/h increments every 30 minutes, to a maximum of 400 mg/h as tolerated (about 3.25 hours in total Published data suggest that a 90 minute infusion (20% of the dose in the first 30 min then the remaining 80% over 60 min)

45. Practice Tips Rituximab & Hepatitis B Reactivation Baseline hepatitis panel Due to the possibility of viral reactivation , hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (HBcAb) should performed on all patients receiving rituximab or other anti-CD20 monoclonal antibodies. Prophylactic antiviral therapy is recommended for any patient who is HBsAg or HBcAb positive and receiving anti-lymphoma therapy, regardless of viral load or presence of clinical manifestation of HBV reactivation. Entecavir is preferred over lamivudine due to concerns of resistance Monitor viral load via PCR Continue prophylaxis for up to 12 months after treatment completed

46. Bendamustine

47. Bendamustine Bendamustine is a mechlorethamine derivative containing a purine-like benzimidazole ring and is an alkylating agent . Contraindications Patients with CrCl < 40ml/min moderate/severe hepatic impairment Sever infections

48. P r epa r a tion Bendamustine Injection: 100 mg DO NOT administer as an IV push or bolus. Dilute with 20 ml SWFI to a final concentration of 0.2 - 0.6 mg/mL in 500 mL infusion bag of 0.9% sodium chloride or 2.5% dextrose/0.45% sodium chloride. Reconstituted solution must be transferred to infusion bag within 30 minutes of reconstitution. CLL: 30 min infusion, NHL: 60 min infusion

49. I n t e r actions CYP1A2 inhibitors (e.g. ciprofloxacin) CYP1A2 inducers (e.g. omeprazole, smoking)

50. Stage II, Bulky ‐Stage III, IV (Grade 1or 2) Indicated for treatment Treatment Protocols: 1- BR R-CHOP R-CVP

51. Treatment Protocols Elderly patients unable to tolerate more aggressive therapy: Rituximab 375 mg/m² x 4 --- weekly doses (preferred) Single-agent alkylators (chlorambucil or cyclophosphamide) +/- rituximab

52. Stage I ‐ IV (Grade 3A or 3B) R- CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) R- CHOP q21days (6-8 cycles) -Rituximab 375 mg/m² D1 C = cyclophosphamide 750 mg/m² IV D1 H = doxorubicin 50 mg/m² IV D1 O = vincristine 1.4 mg/m² IV D1 (cap at 2mg) P = prednisone 100 mg PO D1-5

53. First-line consolidation D (Rituximab every 2 months x 2 years) (Category 1) First-line consolidation / extended therapy for advanced disease after frontline therapy If initially treated with single-agent rituximab, consolidation with rituximab 375 mg/m² every 8 weeks for 4 doses

54. Relapsed FL After progressing from first line therapy, some patients will still benefit from observation. Indications for treatment include symptomatic disease Progressive disease should be histologically documented to exclude transformation to DLBCL

55. 1- B-Cell NHL B. Aggressive I. Diffuse Large B‐cell Lymphoma

56. Diffuse Large B‐cell Lymphoma Most common lymphoid neoplasm in adults Approximately 30% of all NHLs diagnosed annually The goal of treatment = CURE Survival is months if left untreated Newly diagnosed patients treated according to the following categories: Stage I & II, non‐bulky disease Stage I & II, bulky disease Stage III & IV disease

57. Treatment of DLBCL The standard first‐line therapy: R-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone). R-CHOP q21days R = rituximab 375 mg/m² IV D1 C = cyclophosphamide 750 mg/m² IV D1 H = doxorubicin 50 mg/m² IV D1 O = vincristine 1.4 mg/m² IV D1 (cap at 2mg) P = prednisone 100 mg PO D1-5 Doxorubicin may be given as continuous IV infusion (CIVI) to decrease risk for cardiotoxicity

58. Treatment Overview of DLBCL Treatment duration dependent upon stage and size Stage I & II, non‐bulky disease —R‐CHOP x 3 cycles + radiation therapy (RT) Stage I & II, bulky disease —R‐CHOP x 6 cycles ± RT Stage III & IV disease —R‐CHOP x 6 cycles ± RT No role for maintenance rituximab

59. DLBCL in the Elderly Poor LVEF or frail R‐CEPP (Rituximab, cyclophosphamide, etoposide, procarbazine and prednisone) R‐CDOP (R- CEOP = rituximab, cyclophosphamide, etoposide, vincristine and prednisone) DA‐R‐EPOCH (Dose adjusted) (rituximab, etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin) (doxorubicin maintained at base dose) R‐CEOP (rituximab, cyclophosphamide, etoposide, vincristine and prednisone ) R‐mini‐CHOP Patients >80 years of age with co‐morbidities R‐mini‐CHOP R‐GCVP (rituximab, gemcitabine, cyclophosphamide, vincristine and prednisolone. )

60. CNS Involvement in DLBLC Risk of CNS involvement is low but possible Prophylaxis: IT MTX or cytarabine Treatment: Systemic MTX +/‐ IT MTX or cytarabine

61. Relapsed DLBCL 40% of patients still experience early treatment failure Defined as refractory disease or relapse after initial response to chemotherapy —Particularly after treatment with R‐CHOP The goal of treatment = CURE Chemotherapy + autologous hematopoietic stem cell transplant (HSCT) Chemotherapy alone (Chemotherapy regimens include R‐Gem/Ox, B‐R, lenalidomide + rituximab)

62. 1- B- Cell NHL C. Very Aggressive I. Burkitt Lymphoma

63. Burkitt Lymphoma Extremely aggressive B‐cell lymphoma Fastest growing human tumor Patients will die within weeks if left untreated Diagnosed in children and adults – Uncommon in adults

64. Treatment Overview of BL Goal of treatment = CURE CHOP or R‐CHOP is NOT ADEQUATE TREATMENT The difference between low-risk disease and high-risk disease is the number of chemotherapy cycles that can be given. Treatment options include: CALGB 10002 regimen CODOX‐M +/‐ rituximab x 3 cycles DA‐R‐EPOCH (minimum of 3 cycles, with 1 additional cycle after CR) R‐HyperCVAD alternating with R‐Methotrexate/Ara‐C x 6 Cycles All BL patient should receive intrathecal prophylaxis in addition to the specific chemotherapy regimen

65. CODOX‐M +/‐ rituximab Day 1: Cyclophosphamide 800mg/m 2 IV + doxorubicin 40mg/m 2 IV Days 2–5: Cyclophosphamide 200mg/m 2 /day IV Days 1 and 3: Cytarabine 70mg intrathecally Days 1 and 8: Vincristine 1.5mg/m 2 IV Day 10: Methotrexate 1,200mg/m 2 IV over 1 hour, then 240mg/m 2 /hour continuous IV infusion for the next 23 hours Day 11: Leucovorin 192mg/m 2 IV 36 hours after initiation of MTX, followed by leucovorin 12mg/m 2 IV every 6 hours until MTX level <5 x10 – 8 M Day 13: G-CSF 5µg/kg SC daily beginning 24 hours after initiation of leucovorin until absolute granulocyte count ≥1 x 10 9 /L Day 15: Methotrexate 12mg intrathecally Day 16: Leucovorin 15mg orally given 24 hours after intrathecal MTX, ± Day 1: Rituximab 375mg/m 2 IV. Repeat cycle every 21 days for 3 cycles.

66. Relapsed BL No definitive second‐line regimens exist Clinical trial preferred Limited data with: DA‐R‐EPOCH R‐IVAC R‐ICE R‐GDP

67. 2- T- Cell NHL A- Cutaneous T-cell lymphoma

68. Cutaneous T‐cell Lymphoma Early‐stage disease – skin directed therapies – Topical corticosteroids, topical chemotherapy, local radiation or topical retinoids Systemic therapies reserved for advanced stages or failure of multiple skin‐directed therapies The administration of sequential, single-agent chemotherapy is preferred over combination regimens.

69. Alemtuzumab(Cambath®) Anti-CD52 monoclonal antibody Escalate to 30 mg IV or subq 3 times per week for up to 12 weeks (usually start with 3 mg for dose 1, 10 mg for dose 2, 30 mg for dose 3. Toxicities: Cytopenias, infusion reactions, infections (CMV), nausea, emesis, fatigue.

70. Supportive Care of CTCL Pruritis Topical moisturizers & emollients Systemic antihistamines, gabapentin Refractory symptoms: aprepitant, naloxone, mirtazapine or SSRIs Infection prophylaxis (Staph aureus)

71. 2- T- Cell NHL B- Peripheral T-cell lymphoma

72. Peripheral T‐cell Lymphoma Arise from mature T‐cells of post‐thymic origin Relatively uncommon – 10% of NHL cases Prognosis is poor compared to B‐cell NHL – Lower response rates and less durable responses to standard combination chemotherapy

73. Treatment: PTCL Anthracycline‐based chemotherapy is backbone CHOP ± radiotherapy CHOEP‐21 DA‐EPOCH Rituximab is not given – T‐cells are typically not CD20 (+)

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