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Cytokine Release Syndrome (CRS): IMDELLTRA® can cause CRS
including serious or life-threatening
reactions. In the pooled safety population, CRS occurred in 55% of patients who received
IMDELLTRA®, including 34% Grade 1, 19% Grade 2, 1.1% Grade 3 and 0.5%
Grade 4. Recurrent CRS occurred in 24% of patients, including 18% Grade 1 and 6% Grade 2.
Most events (43%) of CRS occurred after the first dose, with 29% of patients experiencing any
grade CRS
after the second dose and 9% of patients experiencing CRS following the third dose or later.
Following the Day 1, Day 8, and Day 15 infusions, 16%, 4.3% and 2.1% of patients experienced ≥
Grade 2 CRS, respectively. The median time to onset of all grade CRS from most recent dose of
IMDELLTRA® was 13.5 hours (range: 1 to 268 hours). The median time to
onset of ≥ Grade 2 CRS from most recent dose of IMDELLTRA® was 14.6
hours (range: 2 to 566 hours).
Clinical signs and symptoms of CRS included pyrexia, hypotension, fatigue, tachycardia, headache,
hypoxia,
nausea, and vomiting. Potentially life-threatening complications of CRS may include cardiac
dysfunction,
acute respiratory distress syndrome, neurologic toxicity, renal and/or hepatic failure, and
disseminated
intravascular coagulation (DIC).
Administer IMDELLTRA® following the recommended step-up dosing and
administer concomitant
medications before and after Cycle 1 IMDELLTRA® infusions as
described in Table 3 of the Prescribing
Information (PI) to reduce the risk of CRS. Administer IMDELLTRA® in
an appropriate health care facility
equipped to monitor and manage CRS. Ensure patients are well hydrated prior to administration of
IMDELLTRA®.
Closely monitor patients for signs and symptoms of CRS during treatment with IMDELLTRA®. At the first sign
of CRS, immediately discontinue IMDELLTRA® infusion, evaluate the
patient for hospitalization and institute
supportive care based on severity. Withhold or permanently discontinue IMDELLTRA® based on severity.
Counsel patients to seek medical attention should signs or symptoms of CRS occur.
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Neurologic Toxicity, Including ICANS: IMDELLTRA® can cause
serious or life-threatening neurologic toxicity,
including ICANS. In the pooled safety population, neurologic toxicity, including ICANS, occurred
in 47% of patients who received IMDELLTRA®, including 10% Grade 3.
The most frequent neurologic toxicities were headache (14%), peripheral neuropathy (7%),
dizziness (7%), insomnia (6%), muscular weakness (3.7%), delirium (2.1%), syncope (1.6%), and
neurotoxicity (1.1%).
ICANS occurred in 9% of IMDELLTRA®-treated patients. Recurrent ICANS
occurred in 1.6% of patients. Most patients experienced ICANS following Cycle 2 Day 1 (24%).
Following Day 1, Day 8, and Day 15 infusions, 0.5%, 0.5% and 3.7% of patients experienced ≥ Grade 2 ICANS, respectively. The median time to
onset of ICANS from the first dose of IMDELLTRA® was 29.5 days
(range: 1 to 154 days). ICANS can occur several weeks following administration of IMDELLTRA®. The median time to resolution of ICANS was 33 days (range: 1 to 93
days).
The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of
CRS.
Clinical signs and symptoms of ICANS may include but are not limited to confusional state,
depressed level
of consciousness, disorientation, somnolence, lethargy, and bradyphrenia.
Patients receiving IMDELLTRA® are at risk of neurologic adverse
reactions and ICANS resulting in depressed
level of consciousness. Advise patients to refrain from driving and engaging in hazardous
occupations or
activities, such as operating heavy or potentially dangerous machinery, in the event of any
neurologic
symptoms until they resolve.
Closely monitor patients for signs and symptoms of neurologic toxicity and ICANS during
treatment. At the
first sign of ICANS, immediately evaluate the patient and provide supportive therapy based on
severity.
Withhold IMDELLTRA® or permanently discontinue based on severity.
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Cytopenias: IMDELLTRA® can cause cytopenias including
neutropenia, thrombocytopenia, and anemia. In the
pooled safety population, decreased neutrophils occurred in 12% including 6% Grade 3 or 4 of
IMDELLTRA®-treated patients. The median time to onset for Grade 3 or
4 neutropenia was 29.5 days (range: 2 to 213). Decreased platelets occurred in 33% including
3.2% Grade 3 or 4. The median time to onset for Grade 3 or 4 decreased platelets was 50 days
(range: 3 to 420). Decreased hemoglobin occurred in 58% including 5% Grade 3 or 4. Febrile
neutropenia occurred in 0.5% of patients treated with IMDELLTRA®.
Monitor patients for signs and symptoms of cytopenias. Perform complete blood counts prior to
treatment with IMDELLTRA®, before each dose, and as clinically
indicated. Based on the severity of cytopenias, temporarily withhold, or permanently discontinue
IMDELLTRA®.
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Infections: IMDELLTRA® can cause serious infections, including
life-threatening and fatal infections.
In the pooled safety population, infections, including opportunistic infections, occurred in 41%
of patients who received IMDELLTRA®. Grade 3 or 4 infections occurred
in 13% of patients. The most frequent infections were COVID-19 (9%, majority during the COVID-19
pandemic), urinary tract infection (10%), pneumonia (9%), respiratory tract infection (3.2%),
and candida infection (3.2%).
Monitor patients for signs and symptoms of infection prior to and during treatment with
IMDELLTRA® and
treat as clinically indicated. Withhold or permanently discontinue IMDELLTRA® based on severity.
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Hepatotoxicity: IMDELLTRA® can cause hepatotoxicity. In the
pooled safety population, elevated ALT occurred in 42%, with Grade 3 or 4 ALT elevation
occurring in 2.1%. Elevated AST occurred in 44% of patients, with Grade 3 or 4 AST elevation
occurring in 3.2%. Elevated bilirubin occurred in 15% of patients; Grade 3 or 4 total bilirubin
elevations occurred in 1.6% of patients. Liver enzyme elevation can occur with or without
concurrent CRS. Monitor liver enzymes and bilirubin prior to treatment with IMDELLTRA®, before each dose, and as clinically indicated. Withhold
IMDELLTRA® or permanently discontinue
based on severity.
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Hypersensitivity: IMDELLTRA® can cause severe hypersensitivity
reactions. Clinical signs and symptoms of hypersensitivity may include, but are not limited to,
rash and bronchospasm. Monitor patients for signs and symptoms of hypersensitivity during
treatment
with IMDELLTRA® and manage as clinically indicated. Withhold or
consider permanent discontinuation of
IMDELLTRA® based on severity.
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Embryo-Fetal Toxicity: Based on its mechanism of action, IMDELLTRA® may cause fetal harm when
administered to a pregnant woman. Advise patients of the potential risk to a fetus. Advise
females of
reproductive potential to use effective contraception during treatment with IMDELLTRA® and for 2 months
after the last dose.
This indication is approved under accelerated approval based on overall response rate and duration of
response. Continued approval for this indication may be contingent upon verification and description of
clinical benefit in a confirmatory trial(s).
