lymphoma

Question 1

risk factors

Answer 1

male
older age
immunosuppression
infections
environmental exposures
radiation exposure
epstein-barr virus
HIV infection

Question 2

non hodgkins lymphoma epidemiology

Answer 2

B cell most common
-diffuse large B cell
-follicular
-mantle cell
-small lymphocytic/ CLL

Question 3

diffuse large B cell lymphoma epidemiology

Answer 3

median age: 66 years
curable disease

Question 4

DLBCL clinical presentation

Answer 4

B symptoms (fever, night sweats, significant weight loss)
nodal mass
elevated lactate dehydrogenase
bone marrow involvement
altered mental status
lab abnormalities: serum creatinine, uric acid, liver enzymes, electrolytes

Question 5

DLBCL diagnosis

Answer 5

lymph node biopsy to confirm *CD20
Imaging: PET scan, CT scan
subtypes: germinal center B-cell (improved outcomes), activated Bcell
*cell of origin/subtype does not determine treatment choice yet

Question 6

DLBCL treatment

Answer 6

preferred: R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)
other: DA-R-EPOCH (dose adjusted rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin)

Question 7

CHOP

Answer 7

high emetic risk
moderate febrile neutropenia risk : consider G-CSF who are high risk

Question 8

rituximab

Answer 8

anti-CD20 monoclonal antibody
ADE: infusion reactions- premedicate with antipyretic and antihistamines, hepatitis B viral reactivation- if positive must use entecavir

Question 9

DA-R-EPOCH

Answer 9

6 cycles
treatment of choice in double or triple hit high grade B cell lymphomas- C-MYC, BCL2, and +/- BCL6 translocations
must give G-CSF following completion of chemotherapy

Question 10

polatuzumab vedotin

Answer 10

ADC is a microtubule-disrupting agent
given with rituximab, cyclophosphamide, doxorubicin and prednisone
-vincristine removed
ADEs; constipation, skeletomuscular pain, peripheral neuropathy, thrombocytopenia, neutropenia

Question 11

relapse/ refractory treatment

Answer 11

salvage chemo: R-ICE, GDP (gemcitabine, dexamethasone, carboplatin)
autologous stem cell transplant
chimeric antigen receptor therapy
bispecific monoclonal antibody

Question 12

CLL

Answer 12

characterized by accumulation of immunologically dysfunctional mature B lymphocytes
most common type of leukemia
up tp 50% do not require treatment at time of diagnosis

Question 13

CLL clinical presentation

Answer 13

asymptomatic at diagnosis
symptomatic
-enlarged lymph nodes
-enlarged spleen or liver
-B symptoms
-autoimmune cytopenia : hemolytic anemia or ITP
-hypogammaglobulinemia leading to frequent infections

Question 14

indications for treatment

Answer 14

*disease related constitutional symptoms: severe fatigue, unintended weight loss, night sweats, and or fever without infection
*threatened end organ function
*progressive bulky disease: symptomatic splenomegaly or lymphadenopathy
*progressive bone marrow failure- worsening anemia +/- thrombocytopenia
*autoimmune anemia or thrombocytopenia that is unresponsive to treatment with corticosteroids or other standard therapies
*an increase in absolute lymphocyte count >50% over a 2 month period, or lymphocyte doubling time of <6 months
*symptomatic extra-nodal involvement (skin, kidney, lung, spine)

Question 15

Treatment

Answer 15

Identify whether patient has del (17p)/TP53 mutation (FISH/NGS)–> assess IGHV mutational status, fitness, age, comorbidities to determine treatment options

fixed duration treatment–> younger and /or fit patients (lack of co-morbidities, no renal impairment)

indefinite treatment–> elderly and/or less fit patients, patient preference

Question 16

treatment options

Answer 16

fixed duration treatment: venetoclax + obinutuzumab

indefinite treatment, normal TP53: acalabrutinib +/- obinutuzumab, zanubrutinib

Abberant TP53/del (17p): indefinite treatment: covalent BTK inhibitors–> acalabrutinib +/- obinutuzumab , zanubrutinib

Question 17

obinutuzumab

Answer 17

2nd gen anti CD20 monoclonal antibody
MOA: antibody dependent cellular cytotoxicity, complement dependent cytotoxicity, antibody dependent phagocytosis, direct cell death through activation of lysosomes

ADEs: infusion related reaction, hepatitis B reactivation, increased risk of viral infections

Question 18

bruton tyrosine kinase inhibitors

Answer 18

BTKis block the B cell receptor signaling cascade by binding to the BTK enzyme and preventing the proliferation and survival of malignant and normal B cell
Second gen BTKis designed to more selectively bind to cysteine 481 in the kinase domain and therefore have less “off target” effects than ibrutinib

Question 19

ibrutinib

Answer 19

reduced dose for mild/moderate & avoid in severe hepatic impairment and w strong CYP3A4 inh/ind