18 - Cancer Immunotherapies Flashcards
Naming Monoclonal Antibodies
Prefix
Unique Sounding Name
Substem A
Indicates TARGET/Disease Class
Substem B
Indicates the SOURCE of AB
xi = Chimeric // xizu = chim-human // ZU = HUMANIZED
- *Suffix**
- mab for monoclonal antibodies
Rituximab
Tumor Directed Monoclonal Antibodies
1st FDA approved MAB to treat cancer
B-cell Non-Hodkin’s Lymphoma
Targets CD-20 = B-cell surface AG
Clinical Considerations:
Infusion related RXN = Chimeric (-xi)
Hepatitis B Reactivation
Tumor Lysis Syndrome (allopurinol for prophylaxis)
RituximabHYCELA
SUBCUTANEOUS INJECTION
version of Rtuximab
LESS INCIDENCE OF INFUSION RELATED REACTIONS
Moderate Infusion Reaction
Tumor Directed Monoclonal Antibodies
STOP infusion –> measure vitals
Administer:
Corticosteroids
+/-
H1/H2 blockers if sysmptoms persist
SEVERE Infusion Reaction = Anaphylaxis
Tumor Directed Monoclonal Antibodies
Stop Infusion -> measure vitals
Aminister:
Hydration + Corticosteroids +/- H1-2 Blockers
EPINEPHRINE + BRONCHODIALATORS
RECHALLENGE
in context of desensitization
Antibody-Drug Conjugates
Tumor Directed Monoclonal Antibodies
Antibody LINKED w/ CYTOTOXIC AGENT
AB –> targeted towards tumor tissue
Linker –> labile connection between both
Cytotoxic Agent –> kills target cells
normally toxic agent, but directed towards tumor tissue
DELIVERS CYTOTOXIC AGENT INSIDE THE CELL
Ex.
Kadcycla
Anti CTLA-4 Antibody
ImmunoTherapy - Monoclonal Antibodies
Ipilimumab
AB that Targets CTLA-4 –> STOPS inhibition of T-cell Killing
Allows for CD28–>B7 = Costim signal
FATAL IMMUNE RELATED ADVERSE REACTIONS
6 Main groups:
LEGS + Hep/Neurologic
Pharmacists are CRITICAL in educationg patients of the Signs & symptoms of ADRs
- *FATAL IMMUNE-related ADR’s** of
- *Ipilimumab** = Monoclonal AB to CTLA-4
Dermatologic
LEGS + HEP/Neurologic
Skin = Most common
Pruitis / Rash
Manage w/ Oral Antipuritics
- *Grade 3/4
- -> TOPICAL +/- ORAL CORTICOSTEROIDS**
- *FATAL IMMUNE-related ADR’s of**
- *Ipilimumab** = Monoclonal AB to CTLA-4
GASTROINTESTINAL
LEGS (reverse) + Hep/Neuro
Rule out other causes first
S/Sx:
Diarrhea / Ab Pain / Blood+mucus in Stool / Ileus
Management:
CORTICOSTEROIDS for prolonged Grade 2 (>1week)
or any grade 3/4
DISCONTINUE for GRADE 3/4
- *FATAL IMMUNE-related ADR’s of**
- *Ipilimumab** = Monoclonal AB to CTLA-4
ENDOCRINE
LEGS (reverse) + Hep/Neuro
Monitor: TSH Q6 weeks // T4 prn
Affects:
Pituitary / Adrenal Glands / Thyroid
S/Sx:
Fatigue / Headache / Abnormal Thyroid Test / Hypotension
Management:
- *WITHOLD TREATMENT**
- *Treat Thyroid issue**
FATAL IMMUNE-related ADR’s of
Ipilimumab = Monoclonal AB to CTLA-4
PULMONARY (Lungs)
LEGS (reverse) + Hep/Neuro
Monitor:
S/Sx of Dyspnea / Cough or SOB
Pneumonitis
onset is 2-3 mo after initiation
Management:
- *WITHOLD TREATMENT**
- *CORTICOSTEROIDS**
- *FATAL IMMUNE-related ADR’s of**
- *Ipilimumab =** Monoclonal AB to CTLA-4
Hepatic / Neurologic
LEGS (reverse) + Hep/Neuro
Hepatic:
LFT prior to each dose
Neurologic:
S/Sx of NUMBNESS / Tingling / Weakness
What does:
RECIST / iRECIST
measure?
MEASURES THE RESPONSE
to the immunotherapy
uiCR: disappearance of all lesions
uiPR: ≥ 30% decrease from baseline
uiSD: When neither PR nor PD can be established
uiPD: ≥ 20% increase from the nadir of total tumor burden
uiUPD: Unconfirmed progressive disease
uiCPD: Confirmed progressive disease
PSEUDOPROGRESSION
ACUTE RISE –> then DROP
After Immunotherapy
PD-1 / PD-L1 ANTAGONIST
Monoclonal ANtibodies
Cancer Cell’s PD-L1 –> T-cell’s PD-1
results in Negative Regulation of T-cell –> Stop Killing = Anergy
Monoclonal Antibodies INHIBIT the interaction
to continue T-cell activation / tumor cell death
Dosing Q3-4 Weeks
- *AVOID STEROIDS**
- reduce the T-cell count, need to inhibit the T-cells*
ADR are less severe than Ipilimumab
Monitoring / Toxicity Management is SIMILAR
Co-Administration of
AB’s for PD-1 /PD-L1 & CTLA-4
GREAT RESULTS
- BUT*
- *Greater TOXICITY / ADR**
- *BiTEs**
- *Bi-Specific T-cell Engagers**
BLINATUMOMAB
Combination via Linker of:
CD-19 Single Chain AB + CD-3 AB
Connects T-CELLS to B-CELLS
Indicated for ALL
Continuous Infusion for 28 days –> 14 days off
ADR:
CYTOKINE RELEASE SYNDROME
Neurotoxicity
CYTOKINE RELEASE SYNDROME
ADR of
BiTEs = Blinatumomab
Occurs when:
LARGE # of lymphocytes activate –> CYTOKINE RELEASE
IFN-Y / TNF-A
IL’s 2 - 6 - 8 - 10
Symptom onset = Days - Weeks
Symptoms:
HA / Fever / Rash
NV / HypoTension / Fatigue
Dyspnea / Tachycardia
TREATMENT for CYTOKINE RELEASE SYNDROME
ADR of BiTEs = Blinatumomab
Grade 1 or 2
Supportive Care
Grade 3 or 4
Supportive Care
TOCILIZUMAB
+/- Corticosteroids
- *TOCILIZUMAB**
- *ACTEMRA**
Treatment for Grade 3/4 CYTOKINE RELEASE SYNDROME
from BiTEs = Blinatumomab
IL-6 Receptor Antagonist
reduces cytokine & acute phase reactant production
IM -> RA
IV -> CART-cell induced cytokine release syndrome
Reverse Dosing = Max -800mg
<30 kg = 12 mg/kg
>30 kg = 8mg/kg
NEUROTOXICITY
ADR of
BiTEs = Blinatumomab
Occurs in 2 OUT OF 3 patients
Symptoms occur within 1st 8 weeks
tied to cytokine release syndrome
Symptoms are Transient, will resolve
Dont drive for 8 weeks
Symptoms:
HA / Encephalopathy / Cognate Fxn
Convulsion / Tremor / Anxiety
Loss of Coordination + Balance
CAR-T Therapy
ADR’s
Cytokine Release Syndrome
79% incidence, avg 3 days to present
Neurotoxicity
Anaphylaxis
due to mouse-derived proteins
“On-Target - OffTumor” Toxicity
failure of b-cell development
Kymriah DOSING
Tisagenlecleucel
- *CAR-T Therapy**
- *DOSE BASED ON CELL COUNT**
- *Premedicate with APAP + DIPHENHYDRAMINE**
- *30-60 min prior to infusion**
ALL < 25 years
≤50 kg: 0.2-5 x 106 CAR-positive viable T cells per kg
>50 kg: 0.1-2.5 x 108 CAR-positive viable T cells per kg
- *DLBC =** diffuse large b-cell cancer
0. 6to 6 x 108 CAR-positive viable T cells (along with chemotherapy)
YESCARTA DOSING
Axicabtagene
CAR-T Therapy
Premedicate w/ APAP 650mg & DIPHENHYDRAMINE 12.5mg
60 min prior
Large B-cell lymphoma
Target does 2 x 106 CAR-positive viable T cells per kg (max: 2 x 108)
DOSE based on CELL COUNT
