PHARM 444: Lymphoma & Multiple Myeloma

what is a Lymphomas?

heterogenous group of lymphoproliferative malignancies originating in lymphocytes and/or lymphatic tissues from T cells, B cells or NK cells.

what are the 2 major categories of lymphoma?

1. Hodgkin Lymphoma (HL) = Malignancy of the Reed-Sternberg cell

2. Non-Hodgkin's Lymphoma (NHL) = ALL other lymphomas (B cell, T cell, NK cells)

what are the different types of Non-Hodgkin's Lymphoma (NHL) (3)

1. B Cell lymphoma

2. T Cell lymphoma

3. NK/T lymphoma

what are the different types of B cell lymphomas (4)

1. diffuse large B cell lymphomas

2. follicular lymphoma

3. chronic lymphatic leukemia/ small lymphocytic lymphoma

4. all other types

what are possible risk factors for Non-Hodgkin's Lymphoma

- weakened immune system

- autoimmune disease

- previous cancer treatment

- family hx. (1st degree relative)

- infections: HIV, EBV (mono), Burkitt, H. pylori & MALT

what are risk factors for Hodgkins Lymphoma

- prolonged EBV infection (mono)

- family hx

- HIV infection

what are "B" symptoms (3)

Fever, night sweats, weight loss

what type of test might you consider for lymphoma diagnosis

- imaging (CT/PET)

- lab test (CBC w/ diff, serum chemistries, LDH etc)

- HIV test

- Hepatitis B

- Pregnancy test

- echocardiogram (IF anthracycline required)

- pulmonary function test (IF bleomycin required)

staging of lymphoma

a) stage 1

b) stage 2

c) stage 3

d) stage 4

a) single lymph node region

b) 2+ lymph node regions SAME side of diaphragm

c) lymph node regions on both sides of diaphragm

d) diffuse involvement with (A) no B sx or (B) with 1 of the B sx

limited vs advanced stage lymphoma

limited = ≤ 3 adjacent lymph node regions

advanced = > 3 LN regions, stage III or IV, B symptoms, or tumour ≥ 10 cm

what is the standard treatment for DLBCL

R-CHOP (rituximab, cyclophosphamide, Hydroxydaunorubicin, Oncovin, prednisone)

Hydroxydaunorubicin/Doxorubicin

a) drug class

b) MOA

c) what is an important counselling point with this medication

d) is a substrate for what enzymes? (2)

e) needs to go into a vein because ...

a) anthracycline

b)

- Inhibition of Topoisomerase II prevents religation of DNA during replication

- Damages DNA / cell membranes by producing free radicals

c) stains body fluids orange/pink (urine and tears)

d) CYP 3A4 & CYP2D6

e) vesicant

Oncovin (vincristine)

a) drug class

b) MOA

c) AE

d) what route of administration can be fatal

e) DI (it is a substrate for what CYP enzyme)

a) Vinca Alkaloid

b) Binds to tubulin (protein on spindle)and prevents mitosis

c)

- constipation

- peripheral neuropathy

- autonomic neuropathy

d) intrathecally

e) CYP3A4

Prednisone monitoring

- blood glucose (especially for diabetic pts)

- mood changes (pts can get grouchy)

- insomnia

- GERD (take with food)

Rituximab

a) drug class

b) MOA

c) AE

d) premedications

e) what needs to be considered being held

f) routes of administration

a) monoclonal aby for CD20

b) destroys B cells

c) infusion reactions

- fever, chills, rigor

- hypotension

- bronchospams

- SOB

- angioedema

d)

- acetaminophen

- diphenhydramine (Benadryl) OR loradtidine

- hydrocortisone

- ranitidine OR famotidine

e) antihypertensives for 12 hours prior

f) IV or subcutaneous

_______ Rituximab CANNOT be used for a patients first dose

Subcutaneous

is premedication still required for subcutaneous Rituximab

YES

is IV and SC dosing of Rituximab based on BSA or flat dosing?

IV = BSA

SC = flat dose

what type of supportive care may be required for DLBCL?

- prophylaxis AINV & breakthrough (antiemetics)

- prophylaxis opportunistic infections

- prophylaxis tumour lysis syndrome

- prophylaxis infusion rxn

Hodgkin lymphoma is a bimodal disease in what age ranges

age 15-30 & 55+

what receptors is expressed in Hodgkins lymphoma (2)

CD15 & CD30

what factors reduce chance of CURE in Hodgkin Lymphoma

- more aggressive stage

- older age (≥45 years old)

- male sex

- abnormal lab results (i.e. high WBC, low albumin, low Hg, high ESR etc)

what is the typical treatment for stages 1-3 Hodgkin Lymphoma ( 4 drug combo)

ABVD

- adriamycin (doxorubicin)

- bleomycin

- vinblastine

- dacarbazine

what is the drug regimen for stage 4 Hodgkin Lymphoma

(hint 2 choices: BV-AVD or Esc-BEACOPP)

BV-AVD

- brentuximab vedotin

- adriamycin (doxorubicin)

- vinblastine

- dacarbazine

Esc-BEACOPP

- bleomycin

- etoposide

- adriamycin (doxorubicin)

- cyclophosphamide

- vincristine (oncovin)

- procarbazine

- prednisone

IF ABVD isn't working (lymphoma isn't going away on PET imaging), patients may switch to ...

Esc-BEACOPP

Esc-BEACOPP has higher risk of long term __________ compared to ABVD.

infertility

Bleomycin

a) MOA

b) AE

c) used in what stage of Hodgkins Lymphoma

a) causes DNA strand scission through formation of an intermediate metal complex

b)

- rash

- hyperpigmentation

- Mucositis

- stomatitis

- Pneumonitis

- pulmonary fibrosis

- loss of appetite

c) Stage 1-4 (ABVD or Esc-BEACOPP)

Vinblastine

a) drug class

b) MOA

c) AE

d) used in what stage of Hodgkins Lymphoma

e) what route of administration is fatal

f) substrate of what enzyme

a) vinca alkaloid

b) Binds to tubulin (protein on spindle) & prevents mitosis

c)

- neurotoxicity

- constipation

- Myelosuppression

d) stage 1-4 (ABVD or BV-AVD)

e) intrathecally

f) CYP 3A4

Dacarbazine

a) MOA

b) AE

c) used in what stage of Hodgkins Lymphoma

a) PRODRUG for MTIC

- methylcarbonum ions that attach nucleopyilic groups in DNA

b)

- N/V (HEC)

- anorexia

- leukopenia

- thrombocytopenia

- infertility risk

c) stage 1-4 (ABVD or BV-AVD)

Procarbazine

a) MOA

b) what needs to be avoided

c) AE

d) used in what stage of Hodgkins Lymphoma

e) duration

a) possibly free radical damage

b)

- high tyramine content food/drink

- alcohol

- sympathomimetic drugs (pseudoephedrine)

c)

- infertility risk

- bone marrow suppression

- secondary malignancies

d) stage 4 (BEACOPP)

e) 7 days of each cycle of chemo

Brentuximab Vedotin

a) drug class

b) MOA

c) AE

d) used in what stage of Hodgkins Lymphoma

e) what is the benefit of using this over bleomycin

a) Antibody-drug conjugate

b) CD30 targeted monoclonal aby attached to cytotoxic drug once internalized MMAE is released which binds to microtubules & disrupts cellular microtubule networks

c)

- Neutropenia

- Peripheral neuropathy

d) stage 4 (BV-AVD)

e) less secondary malignancies & less lung disease

symptoms associated with malignancy associated hypercalcemia

- fatigue, lethargy, weakness, malaise

- obtunded/confusion

- anorexia

- polyuria

- polydipsia

- constipation

- nausea or vomiting

Hypercalcemia of malignancy is common in ....

multiple myeloma & bone metastases (prostate, bone, lung)

what is considered

a) mild hypercalcemia

b) moderate hypercalcemia

c) severe hypercalcemia

d) life threatening hypercalcemia

a) 2.65 - 3.0 mmol/L

b) 3.0 - 3.5 mmol/L

c) 3.5 - 4.0 mmol/L

d) > 4.0 mmol/L

why do we need correct calcium?

calcium = highly protein bound

Therefore when pts are hypoalbuminemia can give less accurate picture of a pts calcium levels

what is the treatment of hypercalcemia

- hydration normal saline

- bisphosphonates

- calcitonin

bisphosphonates

a) indication

b) MOA

c) drug examples (2)

d) onset

a) hypercalcemia

b) enhances serum calcium elimination & inhibits skeletal calcium release by tumours

c) Pamidronate & Zoledronate

d) 1-2 days

calcitonin

a) indication

b) MOA

c) onset

a) hypercalcemia

b) promotes renal excretion of calcium

c) 2-6 hours -- limited to 1st 48 hours due to tachphylaxis

_______ is given to stimulate production and movement of neutrophils out of the bone marrow into the blood stream.

filgrastim

Bone Targeted Therapy can help to reduce fractures and pain. what are possible options

- Pamidronate IV

- Zoledronate IV

- Denosumab SC

- Vitamin D

what is the primary purpose of Autologous HSCT

- to allow dose escalation of chemotherapy = increase tumour cell kill

- serves to "rescue" the patient from myelosuppressive effects of high-dose chemotherapy.

what is stem cell mobiliization?

strategy to move stem cells out of the bone marrow and into the peripheral blood where they are accessible to collect (by apheresis)

What agents are used to mobilize stem cells? (2)

- high dose cyclophosphamide

- filgrastim (7 days later)