Lymphoma Overview Joseph Leach, MD
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1 Lymphoma Overview Joseph Leach, MD
2 71 year old male presents with complaints of mild fa5gue and a visible mass in the le: supraclavicular region PE demonstrates a firm easily palpable mass in the le: supraclavicular fossa but no other significant findings PMH: Sarcoidosis in 1970s, history of paroxysmal atrial fibrilla5on Denies pain, anorexia, weight loss, night sweats Labs are unremarkable.
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4 Lymphoma Lymphoma is a term referring to malignancies arising from lymphoid 5ssues Broad collec5on of diseases with highly variable clinical behavior and prognosis. Generally placed into the following categories: Hodgkin s vs non- Hodgkin s For non- Hodgkin s: Indolent vs aggressive B cell vs T cell Diagnosis historically established based on histology; genomics plays a much more important role in classifica5on and treatment
5 Lymphoma- Staging
6 Lymphoma Clinical workup Workup for suspected lymphoma requires adequate 5ssue for classifica5on and diagnos5c evalua5ons (imaging and blood) to evaluate extent and prognosis FNA does not play a role in diagnosis of lymphoma At minimum core biopsy required but excisional biopsy preferred (and may be required) Imaging includes CT and PET scan, CNS imaging in aggressive lymphoma may be indicated Laboratory studies include CBC and LDH
7 Core biopsy is obtained of the le: supraclavicular node demonstra5ng diffuse large B cell lymphoma, CD20 posi5ve Bone marrow biopsy demonstrates no evidence of bone marrow involvement PET scan performed
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9 Final stage is IVA diffuse large B cell non- Hodgkin s lymphoma Treated with 6 cycles of R- CHOP (rituximab, cyclophosphamide, vincris5ne, doxorubicin, prednisone) PET scan obtained a:er 4 cycles to assess response
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12 Diffuse large B cell lymphoma One of the most common lymphomas (25% of NHL) and the most common aggressive histology Important subsets exist and need to be recognized due to differences in therapy and prognosis Median age at diagnosis is 64 but can occur at all ages About 60% present with advanced disease Clinical presenta5on is quite variable but typically has rela5vely rapidly evolving disease course Extra- nodal involvement is common
13 Diffuse Large B Cell Lymphoma Interna5onal Prognos5c Index is useful for stra5fying prognos5c groups
14 International Prognostic Index (IPI)
15 DLBCL The standard treatment regimen for typical DLBCL is R- CHOP In early stage disease (stage I- II), abbreviated R- CHOP (3-4 cycles) followed by low intensity involved field irradia5on is equal in efficacy In more advanced disease, 6-8 cycles of R- CHOP is standard The goal of therapy is cura5ve; since the introduc5on of rituximab, there is no subset (even high risk IPI) with a cure rate of less than 50% Maintaining dose intensity (full dose treatment given on 5me) improves the likelihood of cure
16 Rituximab Rituximab is a monoclonal an5body directed against CD20 Approved in 1997 for treatment of chemotherapy refractory B cell lymphoma First monoclonal an5body approved for cancer It has become the cornerstone of therapy for B cell malignancy
17 Rituximab
18 Event-free Survival among 399 Patients Assigned to Chemotherapy with Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP) or with CHOP plus Rituximab Coiffier, B. et al. N Engl J Med 2002;346:
19 Rituximab Toxicity is minimal and not synergis5c with chemotherapy Can cause infusion reac5ons, at 5mes severe Does result in immunosuppression and B cell deple5on, increased risk of reac5va5on of hepa55s B Can result in delayed some5mes profound neutropenia
20 41 year old female presented with 3 months of worsening cough, substernal chest pain and onset of hoarseness Exam remarkable for clear hoarseness, markedly distended neck veins Had been feeling slightly fa5gued, 20 pound weight loss Pain exacerbated by alcohol PMH: Benign thyroid nodule Non- smoker Lab: CBC normal, LDH 422
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22 Open biopsy performed, pathology demonstrated diffuse large B cell lymphoma Final diagnosis stage IIB primary medias5nal B cell lymphoma Extremely aggressive disease, infiltra5ve and o:en confined to medias5num Historically high rate of relapse with standard CHOP and radia5on Treated with R- EPOCH x 6 cycles with complete response, remains in remission nearly 3 years out
23
24 Kaplan Meier Estimates of Event-free and Overall Survival of Patients with Primary Mediastinal B-Cell Lymphoma Receiving DA-EPOCH-R, According to Study Group. Dunleavy K et al. N Engl J Med 2013;368:
25 39 year old male history of HIV presented with night sweats, severe abdominal pain and profound fa5gue. Had been off of an5retroviral therapy for 6 months. CT scan performed.
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27 39 year old male history of HIV presented with night sweats and abdominal pain. Had been off of an5retroviral therapy for 6 months. CT scan performed. Biopsy of abdominal mass demonstrated high grade B cell lymphoma, c- myc posi5ve consistent with Burkih s lymphoma Bone marrow biopsy and lumbar puncture nega5ve
28 Burkitt s Lymphoma Extremely aggressive lymphoma, diagnos5c workup and treatment should be pursued urgently (i.e. as inpa5ent) Pathologically characterized by ac5va5on of the c- myc oncogene (most commonly via the t(8;14) transloca5on) Can occur sporadically or in immunocompromised hosts (most commonly HIV) Typically presents as rapidly developing illness with cons5tu5onal symptoms and o:en massive abdominal lymphadenopathy CNS involvement occurs in 15-20% of cases and is common site of relapse
29 Burkitt s Lymphoma Treatment involves intensive chemotherapy u5lizing mul5ple drugs; toxicity is substan5al and administered in the inpa5ent seing CNS prophylaxis essen5al to prevent CNS relapse In HIV pa5ents, HAART is crucial part of management Goal of treatment is cura5ve
30 Burkitt s Lymphoma Pa5ent treated with R- CODOX- M/IVAC plust intrathecal methotrexate and cytarabine plus HAART Treatment associated with significant toxicity including severe mucosi5s, sepsis, renal failure
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33 Tumor Lysis Syndrome True oncologic emergency resul5ng from rapid lysis of bulky malignancy with sudden release of intracellular contents Can results in acute onset of hyperkalemia, hyperphosphatemia Most importantly results in release of nucleic acid with resultant hyperuricemia Marked hyperuricemia leads to uric acid precipita5on in renal tubules and acute renal failure
34 Tumor Lysis Syndrome Occurs typically in aggressive, bulky malignancies and usually triggered by chemotherapy Occasionally in very aggressive malignancies tumor lysis can occur spontaneously from tumor necrosis Heme malignancies are greatest risk, par5cularly Burkih s and acute lymphoblas5c leukemia/lymphoma Rarely occurs in very bulky solid tumors that are highly sensi5ve to chemo (small cell lung cancer)
35 Tumor Lysis Syndrome Important to iden5fy risk factors (high risk histology, elevated LDH, uric acid, renal insufficiency) Must be prevented!! Allopurinol, aggressive hydra5on, alkaliniza5on, chemo modifica5on In very high risk situa5on, rasburicase can be very effec5ve but $$$ Nephrology should be consulted early for considera5on of dialysis if urine output decreases
36 52 year old male presented with cervical and supraclavicular lymphadenopathy CT imaging demonstrated diffuse lymphadenopathy Bone marrow biopsy demonstrated 5% marrow involvement Lymph node biopsy demonstrated grade 2 follicular non- Hodgkin s lymphoma
37 Follicular NHL One of most common types of NHL (35%) Considered indolent disease although considerable variability Histologic grade is important; grade 1-2 are indolent, grade 3 is aggressive with similar prognosis to DLBCL Majority (85%) harbor t(14;18) which ac5vates BCL2 oncogene Confers loss of apoptosis
38 Follicular NHL Goal of therapy is not to cure but to treat cancer associated symptoms and prolong survival Low volume asymptoma5c pa5ents do not need treatment Disease related symptoms, bulky or rapidly progressing disease are indica5ons for treatment No standard treatment; more intensive therapy improves remission rate but unclear if impacts survival
39 Follicular NHL Since asymptoma5c and non- bulky, chose observa5on Over next 6 months begins to experience worsening fa5gue, some night sweats PET imaging pursued
40 Follicular NHL
41 Elected to ini5ate therapy, treated with 6 cycles of R- CVP Tolerated treatment well, symptoms rapidly resolved
42
43 Follicular NHL Maintenance rituximab markedly improves disease free survival; impact on overall survival unclear Mul5ple therapies now available, difficult to es5mate projected survival
44 Figure 2 Kaplan-Meier estimates of progression-free survival (A), time to next antilymphoma treatment (B), time to next chemotherapy (C), and overall survival (D) from randomisation with rituximab maintenance versus observation HR=hazard ratio. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial The Lancet, Volume 377, Issue 9759, 2011,
45 Follicular NHL Elected to treat with maintenance rituximab once every 2 months for 2 years Remains off therapy in remission 3 years out
46 Survival issues Aggressive therapy can be associated with long term risks Cardiomyopathy from anthracyclines Permanent neurotoxicity from vinca alkaloids Secondary malignancy (leukemia) from alkyla5ng agents and anthracyclines Infer5lity Risk of radia5on associated malignancy (breast cancer)
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