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Indication
LUNSUMIO™ (mosunetuzumab-axgb), as a single agent, is indicated for the treatment of adult patients with relapsed or refractory follicular lymphoma who have received at least two prior systemic therapies.
This indication is approved under accelerated approval based on complete response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
Important Safety Information
Warnings and Precautions
Cytokine Release Syndrome
CRS of any grade (American Society for Transplant and Cellular Therapy (ASTCT) grading system) occurred in 39% (84/218) of patients, including Grade 2 in 14%, Grade 3 in 2.3%, and Grade 4 in 0.5% of patients. The one patient with the Grade 4 event was a patient with FL in the leukemic phase and also experienced concurrent TLS. No patients had fatal CRS event. CRS resolved in all patients, and the median duration of CRS events was 3 days (range: 1 – 29 days).
Of the 86 patients that experienced CRS, the most common signs and symptoms of CRS included pyrexia (98%), chills (36%), hypotension (35%), tachycardia (24%), hypoxia (22%), and headache (16%).
Sixteen percent (34/218) of patients received tocilizumab and/or a corticosteroid, 10% (21/218) received tocilizumab, 10% (22/218) received corticosteroids, and 4% (9/218) received both tocilizumab and corticosteroids. In patients experiencing Grade 2 CRS, 48% (16/33) of patients were treated with symptomatic management without corticosteroids or tocilizumab, 33% (11/33) received corticosteroids, 30% (10/33) received tocilizumab and 12% (4/33) received both corticosteroids and tocilizumab. Patients with Grade 3 (n = 5) or Grade 4 (n = 1) CRS received tocilizumab, corticosteroids, vasopressors, and/or oxygen supplementation. Hospitalizations due to CRS occurred in 20% (44/218) of patients and the median duration of hospitalization was 5 days (range: 0 – 30 days).
Premedicate patients with corticosteroids, antipyretics and antihistamines at least through Cycle 2. Ensure adequate hydration prior to the administration of LUNSUMIO. Monitor patients for signs or symptoms of CRS. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time. Institute treatment with supportive care, tocilizumab and/or corticosteroids as indicated. Patients who experience CRS or other events that impair consciousness) should be evaluated and advised not to drive and refrain from operating heavy or potentially dangerous machinery until events resolve.
Serious infections
Serious infections such as pneumonia, bacteremia, and sepsis or septic shock have occurred in patients receiving LUNSUMIO, some of which were life-threatening or fatal events. Febrile neutropenia was observed in patients after receiving LUNSUMIO infusion. Serious infections of any grade occurred in 17% (37/218) of patients including 4 (1.8%) patients experiencing serious infections concurrently with Grade 3 – 4 neutropenia. The median time to onset of first serious infection was 50 days (range: 1-561 days), with median duration of 12 days (range: 2-174 days). Grade 5 events occurred in 0.9% (2/218) patients, which included pneumonia and sepsis. Neutropenia of any grade occurred in 28% (60/218), including 24% Grade 3 – 4 events. The median time to onset of first neutropenia/neutrophil count decreased events was 48 days (range: 1 – 280 days), with median duration of 8 days (range: 1 – 314 days). Of the 60 patients who had neutropenia/neutrophil count decreased events 68% (41/60) received treatment G-CSF to treat the events.
LUNSUMIO should not be administered in the presence of active infections. Caution should be exercised when considering the use of LUNSUMIO in patients with a history of recurring or chronic infections (e.g., chronic, active Epstein-Barr Virus), with underlying conditions that may predispose to infections or who have had significant prior immunosuppressive treatment. Administer prophylactic antibacterial, antiviral and/or antifungal medications, as appropriate. Monitor patients for signs and symptoms of infection before and after LUNSUMIO administration and treat appropriately. In the event of febrile neutropenia, evaluate for infection and manage with broad spectrum antibiotics, fluids and other supportive care.
Tumor flare
Tumor flare (including pleural effusion and tumor inflammation) occurred in 4% (9/218) of patients, including Grade 2 in 1.8% and Grade 3 in 2.3% of patients. The median time to onset was 13 days (range: 5 – 84 days), and median duration was 10 days (range: 1 – 77 days). Manifestations included new or worsening pleural effusions, localized pain and swelling at the sites of lymphoma lesions and tumor inflammation.
Consistent with the mechanism of action of LUNSUMIO, tumor flare is likely due to the influx of T cells into tumor sites following LUNSUMIO administration.
There are no specific risk factors for tumor flare that have been identified, however, there is a heightened risk of compromise and morbidity due to mass effect secondary to tumor flare in patients with bulky tumors located in close proximity to airways and/or a vital organ. Monitoring and evaluation for tumor flare at critical anatomical sites is recommended in patients treated with LUNSUMIO.
Tumor Lysis Syndrome (TLS)
TLS occurred in 0.5% (2/414) of patients, concurrent with CRS. One patient with follicular lymphoma was in the leukemic phase who experienced Grade 4 TLS. TLS onset was on days 2 and 24, and resolved within 3 and 6 days, respectively.
Ensure adequate hydration prior to the administration of LUNSUMIO. Administer prophylactic anti-hyperuricemic therapy (e.g allopurinol, rasburicase), as appropriate. Monitor patients for signs or symptoms of TLS, especially patients with high tumor burden or rapidly proliferative tumors, and patients with reduced renal function. Monitor blood chemistries and manage abnormalities promptly.
Most Common Adverse Reactions
The most common adverse reactions (≥ 20%) were cytokine release syndrome (39%), neutropenia (28%), pyrexia (24%), hypophosphatemia (23%) and headache (20%).
Drug Interactions
Physiologically based pharmacokinetics modeling and simulations based on IL-6 and cytochrome P450 (CYP) 3A interaction indicated a low risk of cytokine-mediated drug-drug interaction potential for mosunetuzumab. No dose adjustment for LUNSUMIO is recommended with co-administration of LUNSUMIO with small molecule drugs which are CYP3A substrates.
Upon initiation of LUNSUMIO in patients who are receiving concomitant drugs that are sensitive CYP3A substrates with a narrow therapeutic index, monitor for effect or drug concentration or dose adjust the CYP3A substrate accordingly if warranted.
Use in Specific Populations
Pregnancy
There are no available data with LUNSUMIO use in pregnant women. Based on low placental transfer of antibodies during the first trimester, the mechanism of action and available data of LUNSUMIO, and the data on the anti-CD20 antibody class, the risk for teratogenicity is low. However transient peripheral B-cell depletion and lymphocytopenia have been reported in infants born to mothers exposed to other anti-CD20 antibodies during pregnancy. Studies with LUNSUMIO in non-pregnant animals have demonstrated that prolonged B-cell depletion can lead to increased risk of opportunistic infection, which may cause fetal loss. Transient CRS associated with LUNSUMIO administration may also be harmful to pregnancy. Therefore, LUNSUMIO should be avoided during pregnancy unless the potential benefit to the mother outweighs the potential risk to the fetus.
Lactation
There is no information regarding the presence of LUNSUMIO in human milk, the effect on the breastfed infant, and the effects on milk production. Because human IgG is excreted in human milk, and the potential for mosunetuzumab absorption leading to B-cell depletion is unknown, women should be advised to discontinue breastfeeding during LUNSUMIO therapy.
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 for additional Important Safety Information.
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