Back to the basics
Name some CTLA4, PD-1 and PDL-1 Inhibitors
CTLA4 inhibitors -- Ipililumab, Tremelimumab.
PT-1 inhibitors- Pembro, Nivo, Dostarlimab Tislelizumab Toripalimab
PDL-1 Inhibitors- Durva, Atezo, Avelumab.
Median onset of ICI-mediated colitis?
Dermatitis- 6 weeks
Colitis- 6 to 8 weeks
Transaminitis- 6 to 12 weeks
Endocrine Abnormalities- 2 to 5 months
It is recommended to give diphenhydramine and acetaminophen for the first 4 cycles prior to Avelumab.
True!
Grading of ICI mediated rash?
When do you hold immunotherapy?
Grading: • G1 – BSA < 10%
• G2 – BSA 10-30%
• G3 – BSA >30%
• G4: Life-threatening; generalized exfoliative, ulcerative, bullous, or necrotic lesions (e.g., SJS/TEN, DRESS).
--> Hold for G3-4
What prophylaxis and adjustments are needed for a patient on steroid Therapy?
--> GI prophylaxis, antimicrobial prophylaxis.
--> Stress-dose adjustments if on physiologic replacement for adrenal insufficiency.
--> Monitoring for and management of both short- and long-term adverse effects of corticosteroid agents • Hyperglycemia • Myopathy, muscle wasting • Mood changes and insomnia
--> Monitor for recurrence of immune-related adverse effects.
--> Monitor for signs/symptoms of adrenal insufficiency with taper plan
What is Talimogene Laherparepvec (TVEC)?
MOA?
Indication?
Adverse effects ? any 5?
--> Oncolytic viral (herpesvirus) immunotherapy.
--> It is essentially a genetically modified herpes simplex virus type 1 designed to selectively infect and kill cancer cells by replicating inside tumor cells causing lysis and releasing tumor-derived antigens into the microenvironment.
-->The virus is engineered to express GM-CSF, attrats Dendritic cells which take up tumor antigens and present them to T cells. This leads to a systemic antitumor immune response, not just against the injected lesion but potentially against distant, uninjected metastases (an abscopal effect).
--> Given as an Intra-tumoral injection.
--> FDA approved 2018 for unresectable stage IIIb-IV melanoma
Adverse effects
Fatigue, Pyrexia, Chills, Flu-like illness, Myalgia/ arthralgia, Herpetic infections, Immune-mediated events, Injection site pain.
All grade incidence of ICI-mediated dermatitis, colitis, transaminitis, and endocrine abnormalities are more with CTLA-4 inhibitors as compared to PD-1/PD-L1 inhibitors.
True!
Grading of ICI colitis?
When do you hold treatment?
G1 (<4 BM >baseline) --Consider holding immunotherapy
G2 (4-6 BM > baseline) --Hold
G3-4 (>6 BM > baseline)--Hold
Name the CART drugs approved in R/R Large Bcell lymphoma?
Namr CART Drugs approved for R/R follicular lymphoma?
--> Axi Cil
--> Liso
--> Tis cel
MOA of Blinatumomab, target and indications?
-Bispecific--CD19-directed CD3 T-cell engager.
-FDA Indication --CD19-positive B-cell precursor ALL with MRD greater than or equal to 0.1% or in R/R CD 19+ B cell ALL.
The ICE (Immune Effector Cell–Associated Encephalopathy) score is used to grade the severity of ICANS, and a decline in this score can precede seizures or cerebral edema.
True
How do you manage grade 2 and 3 colitis?
G-2
- Hold immunotherapy.
- Start with budesonide 9mg daily. If no response, switch to systemic steroids- Prednisone/IV methylprednisolone (1–2 mg/kg/day) {No response to oral steroids after 3 days, consider IV steroids, consider adding infliximab or vedolizumab}
• Consider tofacitinib or ustekinumab for infliximab- and/or vedolizumab refractory colitis
G-3-4 Hold immuno, inpatient admission, start IV methylprednisolone, give it 1–2 days, continue steroids, consider adding infliximab or vedolizumab.
- Consider tofacitinib or ustekinumab for infliximab and/or vedolizumab refractory colitis.
CART Drugs for multiple myeloma?
CART drugs for R/R mantle cell lymphoma?
Multiple myeloma--Cilta cel, Ide cel
R/R mantle cell lymphoma-- Brex cel, Liso cel
MOA OF Epcoritamab and its indications?
MOA of Mosunetuzumab and its indications
Both are Bispecific CD20-directed CD3 T-cell engager
FDA indication of Epcoritamab --Adult patients with R/R DLBCL after 2 or more lines of systemic therapy
FDA indication of Mosunetuzumab is R/R FL after two or more lines of systemic therapy.
Tocilizumab effectively treats both CRS and ICANS because it penetrates the blood–brain barrier.
False !!!!Tocilizumab improves CRS but has limited CNS penetration and does not effectively treat ICANS; corticosteroids are preferred for ICANS
ICI mediated transaminitis. Grading?
G1 (<3xULN) --Consider holding IO
G2 (3-5xULN)--Hold IO
G3 (>5-20xULN) G4 (>20xULN)--Hold IO