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Important Safety Information |
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BOXED WARNING |
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Cytokine release syndrome (CRS), including serious or
life-threatening reactions, can occur in patients receiving LUNSUMIO
or LUNSUMIO VELO. Initiate treatment with the LUNSUMIO or LUNSUMIO
VELO step-up dosing schedule to reduce the risk of CRS. Withhold
LUNSUMIO or LUNSUMIO VELO until CRS resolves or permanently
discontinue based on severity. |
|
Warnings and Precautions |
|
Cytokine Release Syndrome (CRS) |
| LUNSUMIO or LUNSUMIO VELO
can cause CRS, including serious or life-threatening reactions. |
| CRS occurred in 39% of
patients who received LUNSUMIO at the recommended dosage in the
clinical trial (N=218), with Grade 1 CRS occurring in 28%, Grade 2
in 15%, Grade 3 in 2%, and Grade 4 in 0.5% of patients. Among 86
patients who experienced CRS, CRS recurred in 28%. Most cases of CRS
occurred following doses of 1 mg on Cycle 1 Day 1 (15%), 2 mg on
Cycle 1 Day 8 (5%), and 60 mg on Cycle 1 Day 15 (33%). Five percent
of patients experienced CRS after receiving 60 mg on Cycle 2 Day 1
with 1% of patients experiencing CRS following subsequent doses of
LUNSUMIO. |
| The median time to onset of
CRS from the start of administration of LUNSUMIO in Cycle 1 Day 1
was 5 hours (range: 1 hour to 3 days), Cycle 1 Day 8 was 28 hours
(range: 5 hours to 3 days), Cycle 1 Day 15 was 25 hours (range: 0.1
hours to 16 days), and Cycle 2 Day 1 was 46 hours (range: 12 hours
to 3 days). The median duration of CRS was 3 days (range: 1 to 29
days). |
| Clinical signs and symptoms
of CRS occurring in patients receiving LUNSUMIO included, but were
not limited to, fever, chills, hypotension, tachycardia, hypoxia,
and headache. Concurrent neurologic adverse reactions occurred in 6%
of patients and included, but were not limited to, headache,
confusional state, and anxiety. |
| CRS occurred in 30% of
patients who received LUNSUMIO VELO at the recommended dosage in the
clinical trial (N=94), with Grade 1 CRS occurring in 20%, Grade 2 in
7%, and Grade 3 in 2.1%. Among 28 patients who experienced CRS, CRS
recurred in 14% of patients. CRS occurred most commonly after the
first two doses: 19% of patients experienced CRS after the Cycle 1
Day 1 dose, 13% after the Cycle 1 Day 8 dose, and 2.1% after the
Cycle 1 Day 15 dose. |
| The median time to CRS onset
from the start of LUNSUMIO VELO administration was 17 hours (range:
7 to 33 hours) with the Cycle 1 Day 1 dose, and 62 hours (range: 30
to 113 hours) with the Cycle 1 Day 8 dose. CRS resolved in all
patients, after a median duration of 2 days (range: 1 to 15 days).
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| Clinical signs and symptoms
of CRS occurring in patients receiving LUNSUMIO VELO included fever,
hypoxia, chills, tachycardia, and headache. Concurrent neurologic
adverse reactions occurred in 5% of patients and included but were
not limited to headache, dizziness, lethargy, memory impairment, and
peripheral neuropathy. |
| Initiate therapy according
to LUNSUMIO or LUNSUMIO VELO step-up dosing schedule to reduce the
risk of CRS. Administer pretreatment medications to reduce the risk
of CRS, ensure adequate hydration, and monitor patients following
administration of LUNSUMIO or LUNSUMIO VELO accordingly. |
| At the first sign of CRS,
immediately evaluate patients for hospitalization, manage per
current practice guidelines, and administer supportive care;
withhold or permanently discontinue LUNSUMIO or LUNSUMIO VELO based
on severity. |
| Patients who experience CRS
(or other adverse reactions that impair consciousness) should be
evaluated and advised not to drive and to refrain from operating
heavy or potentially dangerous machinery until resolution. |
|
Neurologic Toxicity, including Immune Effector Cell-Associated
Neurotoxicity Syndrome (ICANS) |
| LUNSUMIO or LUNSUMIO VELO
can cause serious and life-threatening neurologic toxicity,
including ICANS. |
| Neurologic toxicity occurred
in 39% of patients who received LUNSUMIO at the recommended dosage
in the clinical trial, with Grade 3 neurologic toxicity occurring in
3% of patients. The most frequent neurologic toxicities were
headache (21%), peripheral neuropathy (13%), dizziness (11%), and
mental status changes (6%, including confusional state, disturbance
in attention, cognitive disorder, delirium, encephalopathy, and
somnolence). ICANS was reported in 1% of patients (Grade 1: 0.5%,
Grade 2: 0.5%) who received LUNSUMIO at the recommended dosage in
the clinical trial. |
| Neurologic toxicity occurred
in 53% of patients who received LUNSUMIO VELO at the recommended
dosage in the clinical trial, with Grade 3 neurologic toxicity
occurring in 1.1% of patients. The most frequent neurologic
toxicities were headache (17%), insomnia (15%), dizziness (10%), and
mental status changes (7%, including confusion and lethargy). ICANS
or suspected ICANS was reported in 3.1% of patients (all Grade 1)
who received LUNSUMIO VELO at the recommended dosage in the clinical
trial. |
| Across a broader clinical
trial population, ICANS or suspected ICANS occurred in 2.2% (21/949)
of patients who received LUNSUMIO or LUNSUMIO VELO. The most
frequent manifestations included confusional state and lethargy.
Twenty patients had Grade 1-2 events and 1 patient had a Grade 3
event. The majority of cases (75%) occurred during the first cycle
of treatment. The median time to onset was 17 days (range: 1 to 48
days). In total, 88% of cases resolved after a median duration of 3
days (range: 1 to 20 days). |
| Coadministration of LUNSUMIO
or LUNSUMIO VELO with other products that cause dizziness or mental
status changes may increase the risk of neurologic toxicity. |
| Monitor patients for signs
and symptoms of neurologic toxicity during treatment. At the first
sign of neurologic toxicity, including ICANS, immediately evaluate
the patient, consider neurology evaluation as appropriate, and
provide supportive therapy based on severity; withhold or
permanently discontinue LUNSUMIO or LUNSUMIO VELO based on severity
and follow management recommendations. |
| Patients who experience
neurologic toxicity such as tremors, dizziness, insomnia, severe
neurotoxicity, or any other adverse reactions that impair
consciousness should be evaluated, including potential neurology
evaluation, and patients at increased risk should be advised not to
drive and to refrain from operating heavy or potentially dangerous
machinery until resolution. |
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Infections |
| LUNSUMIO or LUNSUMIO VELO
can cause serious or fatal infections. |
| Among patients who received
LUNSUMIO at the recommended dosage in the clinical trial, serious
infections, including opportunistic infections, occurred in 17%,
with Grade 3 or 4 infections in 14% and fatal infections in 0.9% of
patients. The most common Grade 3 or greater infections were
pneumonia, sepsis, and upper respiratory infection. |
| Among patients who received
LUNSUMIO VELO at the recommended dosage in the clinical trial,
serious infections, including opportunistic infections, occurred in
17%, with Grade 3 or 4 infections in 16%, and fatal infections in
3.2% of patients. The most common Grade 3 or greater infections were
pneumonia, sepsis, and COVID-19. |
| Monitor patients for signs
and symptoms of infection prior to and during treatment with
LUNSUMIO or LUNSUMIO VELO and treat appropriately. LUNSUMIO or
LUNSUMIO VELO should not be administered in the presence of active
infection. Caution should be exercised when considering the use of
LUNSUMIO or LUNSUMIO VELO in patients with a history of recurring or
chronic infections (eg, chronic, active Epstein-Barr Virus), with
underlying conditions that may predispose to infections, or who have
had significant prior immunosuppressive treatment. Administer
prophylactic antimicrobials according to guidelines. Withhold
LUNSUMIO or LUNSUMIO VELO or consider permanent discontinuation of
LUNSUMIO or LUNSUMIO VELO based on severity. |
|
Hemophagocytic Lymphohistiocytosis (HLH) |
| LUNSUMIO or LUNSUMIO VELO
can cause fatal or serious HLH. HLH is a potentially
life-threatening, hyperinflammatory syndrome that is independent of
CRS. Common manifestations include fever, elevated ferritin,
hemophagocytosis, cytopenias, coagulopathy, hepatitis, and
splenomegaly. |
| Across a broader clinical
trial population, HLH occurred in 0.5% (7/1536) of patients. Most
cases (5/7) were identified within the first 28 days following
initiation of LUNSUMIO or LUNSUMIO VELO, with 3 cases preceded by
diagnosed or suspected CRS. Of the 7 cases of HLH, 6 had fatal
outcomes, with 2 deaths from HLH alone and 4 deaths with concurrent
unresolved HLH. Of the 7 cases of HLH, 4 occurred in the context of
concurrent EBV and/or CMV infection. |
| Monitor for clinical signs
and symptoms of HLH. Consider HLH when the presentation of CRS is
atypical or prolonged, or when there are features of macrophage
activation. For suspected HLH, interrupt LUNSUMIO or LUNSUMIO VELO
and treat promptly for HLH per current practice guidelines. |
|
Cytopenias |
| LUNSUMIO or LUNSUMIO VELO
can cause serious or severe cytopenias, including lymphopenia,
neutropenia, anemia, and thrombocytopenia. |
| Among patients who received
LUNSUMIO at the recommended dosage in the clinical trial, Grade 3 or
4 decreased lymphocytes occurred in 92%, decreased neutrophils in
38%, decreased hemoglobin in 19%, and decreased platelets in 12% of
patients. Grade 4 decreased lymphocytes occurred in 71%, decreased
neutrophils in 19%, and decreased platelets in 5% of patients.
Febrile neutropenia occurred in 2% of patients. |
| Among patients who received
LUNSUMIO VELO at the recommended dosage in the clinical trial, Grade
3 or 4 decreased lymphocytes occurred in 69%, decreased neutrophils
occurred in 26%, decreased hemoglobin in 10%, and decreased
platelets in 10% of patients. Grade 4 decreased neutrophils occurred
in 13% and decreased platelets in 6% of patients. Grade 4 decreased
lymphocytes occurred in 22%, decreased neutrophils in 9%, and
decreased platelets in 3.2% of patients. Febrile neutropenia
occurred in 2.1% of patients. |
| Monitor complete blood
counts throughout treatment. Based on the severity of cytopenias,
temporarily withhold or permanently discontinue LUNSUMIO or LUNSUMIO
VELO. Consider prophylactic granulocyte colony-stimulating factor
administration as applicable. |
|
Tumor Flare |
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LUNSUMIO or LUNSUMIO VELO can cause serious or severe tumor flare.
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| Among patients who received
LUNSUMIO at the recommended dosage in the clinical trial, tumor
flare occurred in 4%. Among patients who received LUNSUMIO VELO at
the recommended dosage in the clinical trial, tumor flare occurred
in 1.1% of patients. Manifestations included new or worsening
pleural effusions, localized pain and swelling at the sites of
lymphoma lesions, and tumor inflammation. |
| Patients with bulky tumors
or disease located in close proximity to airways or a vital organ
should be monitored closely during initial therapy. Monitor for
signs and symptoms of compression or obstruction due to mass effect
secondary to tumor flare. If compression or obstruction develops,
institute standard treatment of these complications. |
| Risk
of Medication Errors with Incorrect Product Use |
| Mosunetuzumab-axgb is
available in two formulations: as an injection for intravenous use
(LUNSUMIO) and as an injection for subcutaneous use (LUNSUMIO VELO).
Check the product labels to ensure that the correct formulation is
being prescribed, dispensed, and administered to the patient. Do not
substitute LUNSUMIO for or with LUNSUMIO VELO. |
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Embryo-Fetal Toxicity |
| Based on its mechanism of
action, LUNSUMIO or LUNSUMIO VELO may cause fetal harm when
administered to a pregnant woman. Advise pregnant women of the
potential risk to the fetus. Verify pregnancy status in females of
reproductive potential prior to initiating LUNSUMIO or LUNSUMIO
VELO. Advise females of reproductive potential to use effective
contraception during treatment with LUNSUMIO or LUNSUMIO VELO and
for 3 months after the last dose. |
|
Most Common Adverse Reactions |
| The most common (≥20%)
adverse reactions of LUNSUMIO are CRS (44%), fatigue (42%), rash
(39%), headache (32%), pyrexia (29%), musculoskeletal pain (28%),
cough (22%), pruritus (21%), and peripheral neuropathy (20%). |
| The most common (≥20%)
adverse reactions of LUNSUMIO VELO are injection site reactions
(69%), fatigue (39%), rash (35%), CRS (30%), COVID-19 infection
(27%), musculoskeletal pain (20%), and diarrhea (20%). |
| The most common Grade 3 to 4
laboratory abnormalities (≥10%) with LUNSUMIO are decreased
lymphocyte count (92%), decreased phosphate (41%), increased glucose
(40%), decreased neutrophil count (38%), decreased hemoglobin (19%),
increased uric acid (15%), and decreased platelets (12%). |
| The most common Grade 3 to 4
laboratory abnormalities (≥15%) with LUNSUMIO VELO are decreased
lymphocyte count (69%), decreased neutrophil count (26%), and
increased uric acid (28%). Grade 4 laboratory abnormalities in
>5% included lymphocyte count decreased (22%) and neutrophil
count decreased (9%). |
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Drug Interactions |
| LUNSUMIO or LUNSUMIO VELO
causes release of cytokines that may suppress activity of CYP450
enzymes, resulting in increased exposure of CYP450 substrates.
Increased exposure of CYP450 substrates is more likely to occur
after the first dose of LUNSUMIO or LUNSUMIO VELO on Cycle 1 Day 1
and up to 14 days after the 60 mg dose of LUNSUMIO on Cycle 2 Day 1
or the 45 mg dose of LUNSUMIO VELO on Cycle 1 Day 8 and during and
after CRS. Monitor for toxicity or concentrations of drugs that are
CYP450 substrates where minimal concentration changes may lead to
serious adverse reactions. Consult the concomitant CYP450 substrate
drug prescribing information for recommended dosage modification.
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Use in Specific Populations |
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Lactation |
| There is no information
regarding the presence of mosunetuzumab-axgb in human milk, the
effect on the breastfed child, or milk production. Because human IgG
is present in human milk, and there is potential for
mosunetuzumab-axgb absorption leading to B-cell depletion, advise
women not to breastfeed during treatment with LUNSUMIO or LUNSUMIO
VELO for 3 months after the last dose. |
| You
may report side effects to the FDA at 1-800-FDA-1088
or www.fda.gov/medwatch.
You may also report side effects to Genentech at 1-888-835-2555.
|
| Please see the LUNSUMIO
full Prescribing
Information and LUNSUMIO VELO full Prescribing
Information for additional Important Safety Information,
including BOXED WARNING. |
| 3L+=third-line or later;
FL=follicular lymphoma. |
| Reference:
1. LUNSUMIO VELO. Prescribing Information. Genentech,
Inc. |
| For Colorado Prescribers: In accordance with
Colorado Law, please access Wholesale Acquisition Cost (WAC) pricing
information here. |
