Exam 3: Lecture 7, Monoclonal Antibodies in the treatment of Cancer Flashcards
3 Mechanisms of MABs….
Block - molecules cancer cells need to grow
Flag - cancer cells for ID by immune system
Deliver - substances to the cancer cell that may kill it
MAB general comments…
most given IV infusion
some can be admin SQ
Some can cause infusion reactions, some pt should be premeditated
standard infusion reactions
Fever/shaking chills flushing/itching HR or BP change Chest, back or abdominal pain Nausea,vomiting,diarrhea skin rash
Standard infusion reactions occur within….
30 min, 2 hrs but can delay up to 24 hr
most common with 1st/2nd dose and incidence declines
Rituximab îs a….
engineered murine/human chimeric monoclonal antibody
1st one approved for cancer
Rituximab MOA
Apoptosis
ADCC (Antibody-dependent cell mediated cytotoxicity)
CDC (complement-dependent cytotoxicity)
Rituximab admin
1st dose: start at 50 mg/hr, can increase by 50mg/hr every 30 min to max of 400 mg/hr
2nd dose: can do 100mg/hr, increase by 100mg/hr until 400 mg/hr
detectable in serum 3-6 months after last dose
Rapid infusion Rituximab
for pt who didn’t experience grade 3/4 infusion-related adverse event during cycle 1, have NHL and BLBCL
used with regimens that include corticosteroid
1st dose = standard dose schedule
subsequent doses 20% over 30 min, then 80% over 1hr
Rituximab black box warnings
infusion reactions
Hep B reactivation
Mucocutaneous reactions
PML
examples of Mucocutaneous reactions Rituximab
Stevens Johnson syndrome, Lichenoid dermatitis, TEN
Onset 1-13 weeks
D/C for severe reactions
PML is a….
rare brain infection with the JC virus that usually causes death/severe disability
no cure/treatment/prevention
How to detect PML
Brain MRI
Lumbar Puncture
Signs/Symptoms = focal neurologic deficits
Tumor lysis syndrome usually occurs in patients who have….
lymphomas or leukemias taking Rituximab
management - hydration, supportive care, dialysis, correct electrolyte abnormalities
pretreat - fluids and allopurinol
onset 12-24hrs after 1st infusion
Other adverse reactions Rituximab….
Myelosuppression
Renal Dysfunction
Do not give live virus vaccine
Rituximab and Hyaluronidase allows for it to be given….
via SQ injection in 5-7 min instead of Iv infusion
can only be given after patients have received at least 1 IV treatment
approved for some indications that rituximab approved for
Trastuzumab MOA
Binds HER2 receptors and inhibits cellular proliferation
Trastuzumab indications
HER2 breast cancer and GI cancer
Trastuzumab admin
** Loading dose ** both therapies
Adjuvant therapy - contine to 52 weeks of therapy
Metastatic disease - until progression/toxicity
Trastuzumab Adverse effects
Infusion reactions most common (20-40%)
cardio toxicity
myelosuppression
embryo-fetal toxicity
Trastuzumab Premedication:
acetaminophen and an antihistamine
for 90 min infusion, glucocortioicd recommended too prior
Trastuzumab Cardiotoxicity
reduce Ejection fraction, cause HF
<10% as single drug
anthracyclines can potentiate
Trastuzumab Cardiotoxicity risks
concurrent or prior anthracyclines or cyclophosphamide
preexisting cardiac disease
prior radiation therapy
old age, smoking, diabetes, thyroid disorders
Trastuzumab and Hyaluronidase combo
lets you give drug SB over 2-5 min
Hyaluronidase mechanism
increased permeability of SQ tissue. effects are reversible and permeability restored within 24-48hrs
How many biosimilars of Trastuzumab?
5
Trastuzumab analog
fam-trastuzumab deruxtecan-nxki (enhertu)
Topoisomerase I inhibit attached to antibody. Binds to HER2, internalized and linker breaks and release DXd which causes DNA damage (Top I inhibitors)
good response but ILD-13% (black box warning)
Ibritumomab (Zevalin) MOA:
serves as carrier for radiation
Ibritumomab indication
patients previously untreated follicular NHL
Ibritumomab Admin Schedule
Day 1: 250 mg/m2 rituximab infusion (premed Benadryl/tylenol)
Day 7,8,or 9: 250mg/m2 rituximab infusion (premed Benadryl/tylenol)
Within 4 hrs, give Ibritumomab
Ibritumomab Precautions
minimize radiation exposure
contraceptives at least 12 months after treatment
wash hands X 3 day
universal precautions for bodily fluids X 3 days
Ibritumomab Adverse effects
Myelosuppression
* more likely than other MABs*
Infusion + Cutaneous reactions
Delayed radiation damage
Bevacizumab MOA:
binds to VEGF preventing reaction with cell receptors
Bevacizumab Dosing
Varies with cancer
ranging 5-15mg/kg IV
1st dose: 90 min
2nd dose: 60min
Later dose: 30 min
Bevacizumab Adverse effects
Impaired wound healing/wound dehiscence (reopening, 28 day precaution)
GI perforation/fistulae
Hemorrhage
Renal injury, proteinuria
Hypertension, monitor BP
Venous thromboembulsims
Bevacizumab contraindicaiton
Squarmous cell lung cancer, 31% serious or fatal bleeding
How many qbiosimilars of Bevacizumab
2
Cetuximab (Erbitux)
targets EGFR and binds to EGFR w/ higher affinity than natural ligands
leads to blocking of signal transduction, inhibit cell growth and lead to apoptosis
K-RAS
if have Wt then EGFR works
if have mutated, then doesnt
Cetuximab (Erbitux) indications
squamous cell carcinoma of Heasd/Neck
K-RAS mutation neg, EGFR expressing colorectal cancer
Cetuximab (Erbitux) admin
1st dose = loading = 400 mg/m2 over 2hr
max rate @ 10mg/min
subsequent weekly doses at 250 mg/m2 over 1hr
premeditate with diphenhydramine
Cetuximab (Erbitux) Adverse effects
Infusion reactions
Severe reactions more common in NC,TN,ARK,MI,VA,FL, due to pt in these states making antibody to galactose-a-1.3 galactose
Pulmonary toxicity and skin toxicity (rash)
Cardiopulmonary arrest/sudden death (Head/neck cancer more likely) - monitor Mg,K,Ca
hypomagnesemia
Immune Checkpoint inhibitors
Newest class of MABs
Immune Checkpoint inhibitors MOA generalities
T cells may be inhibited by a ligand that binds to a specific receptor on the T cell that limits its activation
Drugs may target specific immune checkpoints that are affected by cancer cells to reduce immune activity
Atezolizumab MOA
PDL1 binding agent
targets PDL1 to restore anti tumor Cell activity
Ipilimumab
only Checkpoint inhibitor that doesn’t work on PD1/PDL1
works on CTLA4
Nivolumab major change in indication
Small cell lung cancer removed
Nivolumab admin
30 min IV infusion
240 mg every 2 week or 480 mg every 4
Nivolumab Adverse effects
Infusion reaction
Immune-related adverse effects
Pembrolizumab admin
30 min Iv infusion
200 mg every 3 week until progression or unacceptable toxicity
up to 24 months in pt w/o disease progression all indications except melanoma
children 2mg/kg (up to 200mg) every 3 week
Pembrolizumab adverse effects
Infusion reaction
Immune related adverse effects
Embryo-fetal toxicity
Immune related adverse effect (IRAE)
Most common = fatigue, itching, diarrhea, decreased appetite, rash, dyspnea, constipation, nausea
can happen with any immune checkpoint inhibitors bc can effect normal cells.
Immune related adverse effect checklist
anytime patient receives medication, checklist going over to see if they’ve experienced anything
IRAE more common with….
CTLA-4 inhibitors (Ipilimumab)
Main treatment of IRAEs?
Corticosteroids
Early intervention is key
