Lecture 6.pptx HODGKIN CANCER level 12ph D 20240823GL

PHCL 414 Pharmacotherapy-VIII

1. Hodgkin Lymphoma Dr. Zabih Ullah Ph.D., EFRE (Belgium & Netherlands) Assistant Professor Email: [email protected]

2. introduction it a type of blood cancer that affects the immune system. It specifically affects white blood cells called lymphocytes, which are an important part of your immune system. Lymphoma is also called a cancer of the lymphatic system, or lymphatic cancer.

3. Pathophysiology •Differences in histology have led to the classification of Hodgkin lymphoma or non-Hodgkin lymphoma (NHL) (B- or T-cell lymphocyte markers). Hodgkin Lymphoma: Pathophysiology .B-cell transcriptional processes are disrupted during malignant transformation, preventing expression of B-cell surface markers and production of immunoglobulin messenger RNA. Alterations in the normal apoptotic pathways favor cell survival and proliferation. . Malignant Reed–Sternberg cells overexpress nuclear factor- κ B, which is associated with cell proliferation and antiapoptotic signals. Infections with viral and bacterial pathogens upregulate nuclear factor- κ B. Epstein–Barr virus is found in many, but not all, HL tumors.

4. CLINICAL PRESENTATION • Most patients with HL present with a painless, rubbery, enlarged lymph node in the supradiaphragmatic area and commonly have mediastinal nodal involvement. Asymptomatic adenopathy of the inguinal and axillary regions may also be present. • Constitutional, or “B,” symptoms ( eg , fever, drenching night sweats, and weight loss) are present at diagnosis in approximately 25% of patients with HL.

5. Diagnosis - Diagnosis requires the presence of Reed–Sternberg cells in the lymph node biopsy. history, physical examination, laboratory tests, and radiography, including positron emission tomography (PET). *Pathologic staging is based on biopsy findings of strategic sites ( eg , bone marrow, spleen, and abdominal nodes) *

6. Note Prognosis predominantly depends on age and amount of disease; patients older than 65–70 years have a lower cure rate than younger patients. Patients with limited-stage disease (stages I and II) have a 90%–95% cure rate, whereas those with advanced disease (stages III and IV) have a 60%–80% cure rate

7. treatment

8. Goals of Treatment The goal is to maximize curability while minimizing short- and long-term treatment-related complications. • Treatment options include radiation therapy (RT), chemotherapy, or both ( combinedmodality therapy). The therapeutic role of surgery is limited, regardless of stage. • RT is an integral part of treatment and can be used alone for select patients with early-stage disease , although most patients will receive chemotherapy and radiation. • Long-term complications of RT , chemotherapy, and chemoradiotherapy include gonadal dysfunction, secondary malignancies ( eg , lung, breast, GI tract, and connective tissue), and cardiac disease.

9. Chemotherapy • Treat all stages and risk groups of HL with 8–12 weeks of chemotherapy and then obtain a restaging PET-CT Response to salvage therapy depends on the extent and site of recurrence, previous therapy, and duration of first remission . Choice of salvage therapy should be guided by response to initial therapy and a patient’s ability to tolerate therapy. • Patients who relapse after an initial complete response can be treated with the same regimen, a non–cross-resistant regimen, or high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HSCT)

10. chemotherapy • Lack of complete remission after initial therapy or relapse within 1 year after completing initial therapy is associated with a poor prognosis. Patients with these prognostic factors are candidate Brentuximab vedotin is approved for the treatment of classical Hodgkin lymphoma after failure of autologous HSCT or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not candidates for autologous HSCT, and also for patients with classical Hodgkin lymphoma at high risk of relapse or progression as consolidation therapy after autologous HSCT.

11. Evaluation of the therapy Evaluate therapeutic response based on physical examination, radiologic evidence, PET/computed tomography (CT) scanning, and other baseline findings

12. Non-Hodgkin Lymphoma

13. introduction it a type of blood cancer that affects the immune system. It specifically affects white blood cells called lymphocytes, which are an important part of your immune system. Lymphoma is also called a cancer of the lymphatic system, or lymphatic cancer.

14. Pathophysiology •Differences in histology have led to the classification of Hodgkin lymphoma or non-Hodgkin lymphoma (NHL) (B- or T-cell lymphocyte markers). . Non-Hodgkin Lymphoma: Pathophysiology NHLs are derived from monoclonal proliferation of malignant B or T lymphocytes and their precursors. Current classification schemes characterize NHLs according to cell of origin, clinical features, and morphologic features. Additional immunohistochemical markers, cytogenetic features, and genotypic characteristics may further classify NHL into subtype

15. CLINICAL PRESENTATION Patients present with a variety of symptoms, which depend on site of involvement and whether it is nodal or extranodal . • Adenopathy can be localized or generalized. Involved nodes are painless, rubbery, and discrete and usually located in the cervical and supraclavicular regions. Mesenteric or GI involvement can cause nausea, vomiting, obstruction, abdominal pain, palpable abdominal mass, or GI bleeding. Bone marrow involvement can cause symptoms related to anemia, neutropenia, or thrombocytopenia. 40%present with B symptoms—fever, drenching night sweats, and weight loss.

16. Diagnosis * biopsy of an involved lymph node. Diagnostic workup of NHL is generally similar to that of HL.

17. Note Prognosis depends on histologic subtype and clinical risk factors ( eg , age >60 years, performance status of two or more, abnormal lactate dehydrogenase, extranodal involvement, and stage III or IV disease).

18. treatment

19. Goals of Treatment The goals are to relieve symptoms and, whenever possible, cure the patient of disease while minimizing the risk of serious toxicity. Treatment options include RT, chemotherapy, and biological agents. RT is used for remission induction with early-stage, localized disease and, more commonly, as a palliative measure in advanced disease. • Effective chemotherapy ranges from single-agent therapy for indolent (follicular) lymphomas to aggressive, complex combination regimens for aggressive disease.

20. FOLLICULAR LYMPHOMAS( nhl ) *low grade of lymphoma. Follicular lymphomas occur in older adults, with a majority having advanced disease that includes the chromosomal translocation t(14;18). Clinical course is generally indolent, with median survival of 8–10 years. The natural history of follicular lymphoma is unpredictable, with spontaneous regression of objective disease seen in.

21. Localized Follicular Lymphoma Options for stages I and II follicular lymphoma include locoregional RT and immunotherapy ( ie , rituximab) with or without chemotherapy or RT. • RT is the standard treatment and is usually curative. Chemotherapy is not recommended, unless the patient has high-risk, stage II disease.

22. Advanced Follicular Lymphoma Management of stages II bulky, III, and IV indolent lymphomas is controversial because standard approaches are not curative. Median time to relapse is only 18–36 months. • Therapeutic options are diverse and include watchful waiting, RT, single-agent chemotherapy, combination chemotherapy, biologic therapy, radioimmunotherapy , and combined-modality therapy. Immediate aggressive therapy does not improve survival compared with conservative therapy • Rituximab, a chimeric monoclonal antibody directed at the CD20 molecule on B cells, is one of the most widely used therapies for follicular lymphoma. It is approved for first-line therapy either alone or combined with chemotherapy and as maintenance therapy with stable disease or with partial or complete response following induction chemotherapy

23. note Practice guidelines list rituximab maintenance for up to 2 years as an option in both first- and second-line therapy. Side effect of Rituximab: usually infusion-related, especially after the first infusion, and consist of fever, chills, respiratory symptoms, fatigue, headache, pruritus, and angioedema. Pretreatment with oral acetaminophen, 650 mg, and diphenhydramine, 50 mg, 30 minutes before the infusion is recommended

24. Evaluation of the therapy Evaluate therapeutic response based on physical examination, radiologic evidence, PET/computed tomography (CT) scanning, and other baseline findings

25. AGGRESSIVE LYMPHOMAS

26. introduction which account for approximately 60% of all NHL cases, tend to grow more quickly and produce more symptoms than indolent lymphomas. The most common subtypes of aggressive NHL are: Diffuse large B-cell lymphoma (DLBCL) Anaplastic large-cell lymphoma.

27. Treatment of Localized Disease Stage I and nonbulky stage II should be treated with three or four cycles of rituximab and CHOP (R-CHOP) followed by locoregional RT or six to eight cycles of R-CHOP with no RT. • Consider six cycles of R-CHOP without radiation if disease presents at sites where radiotherapy may lead to significant morbidity .

28. Treatment of Advanced Disease Treat bulky stage II and stages III and IV lymphomas with R-CHOP or rituximab and CHOP-like chemotherapy until achieving complete response (usually 4–6 cycles). Maintenance therapy following a complete response does not improve survival. • Consider high-dose chemotherapy with autologous HSCT in high-risk patients who respond to standard chemotherapy and meet HSCT criteria.

29. Treatment of Refractory or Relapsed Disease Approximately one-third of patients with aggressive lymphoma will require salvage therapy. Salvage therapy is more likely to induce response if the response to initial chemotherapy was complete . • High-dose chemotherapy with autologous HSCT is the therapy of choice for younger patients with chemosensitive relapse. • Commonly used regimens include DHAP (dexamethasone, cytarabine , and cisplatin), ESHAP (etoposide, methylprednisolone, cytarabine , and cisplatin), ICE ( ifosfamide , carboplatin, etoposide), and MINE ( mesna , ifosfamide , mitoxantrone , and etoposide).

30. Treatment of refractory disease Exclude rituximab in second-line therapy if the disease is refractory or if the duration of remission is less than 6 months. -Three chimeric antigen receptor (CAR) T-cell therapies,  tisagenlecleucel , axicabtagene ciloleucel , and lisocabtagene maraleucel have been approved for relapsed and refractory disease after failure of two or more lines of systemic treatment. CAR Tocxities : Associated with a high incidence of cytokine release syndrome including: fever, hypoxia, and hypotension, and may require the use of vasopressors in severe cases. Severe neurological toxicities such as encephalopathy and seizures can also occur.

31. Questions ???