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Who gets Tarlatamab (aka Imdelltra)?
Patients with metastatic small cell lung cancer whose cancer has progressed despite 1 prior lines of treatment (NEJM ref)
What is Tarlatamab? Does it work?
Bispecific T Cell Engager (BiTE) Antibody
One side of the antibody grabs CD3 on the T cell and on the other side grabs DLL3 (expressed on small cell cancer cells). This brings the T cell closer to the cancer and tries to get the T cell to kill the cancer cell (video here)
Leads to shrinkage of cancer in 35% of pts
Better overall survival than chemo (13mo vs 8 mo)
Why do patients who receive Tarlatamab need to be admitted to the hospital?
Tarlatamab can cause Cytokine Release Syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) within the first 24 hours after the infusion so patients need to be monitored/treated for these side effects
It is recommended to calculate a baseline ICE score (immune effector cell-associated encephalopathy score) on admission and document that in sign-out note (SEE TABLE)
What are the signs of CRS and ICANS and how common is it?
CRS: Fever, myalgias, hypotension, hypoxia
In trial (phase 2 reference, phase 3 reference)
42% had just fever, 13% had fever + either hypotension responsive to fluids or hypoxia responsive to O2, 1% had higher grade CRS
Median time to onset= 13 hours (range- 8-27 hours)
7% needed fluids, 8% supplemental O2
16% needed steroids
4% needed tocilizumab, 0.5% needed vasopressors in ICU
ICANS: confusion, impaired attention, weakness, tremor, motor findings
5% of pts in trial had ICANS
Median time to onset= 9-15 days after infusion
How do I treat CRS?
Brief:
Fevers: tylenol
Hypotension: fluids- up to 2L
Hypoxia: Oxygen
If hypotension or hypoxia persist after 2-3 hours, give Dexamethasone 20 mg IV or methylprednisolone 2mg/kg IV once
If symptoms do not improve within 4 hours of dexamethasone, next step is tocilizumab 8mg/kg (max dose 800mg) but attending should be involved in that decision
Additional Resource: Practical Management of Tarlatamab Adverse Events
What do I do if I'm worried about neurotoxicity?
Calculate the ICE score
If ICE score is less than 7 (and was normal at baseline) give dexamethasone 10mg IV (can repeat every 6 hours)
**if severe toxicity (awakens only to tactile stimulus, seizure <5 min, or focal/local edema on imaging) give dex 20 (repeat every 6 hours)
Call Attending
Consider MR Brain
Low threshold to call ICU fellow and/or get neuro consult
Next lines of treatment are siltuximab 11 mg/kg (max 1000 mg) and if that not effective anakinra (400 mg IV x 1 day then 200 mg daily SC up to 7 days)
Above should not be given w/o attending approval
When can the patient be discharged?
Pt should be afebrile and normotensive for 22-24 hours post infusion
Note that the pts receive the infusion in the outpatient setting. Infusion time can be found in the synopsis tab
Patients with persistent recurrent fevers can be discharged if:
No CRS/ICANS intervention in the past 24 hours (i.e. dexamethasone, tocilizumab, fluid boluses, oxygen supplementation, or pressors)
Stable fever curve and no new CRS symptoms
Heart rate <120
At least 24 hours of observation from first sign of CRS
Alternative diagnoses have been considered and ruled out or assessed as unlikely (such as new infection)
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