Mosunetuzumab-axgb is a bispecific monoclonal antibody that is a CD20-directed CD3 T-cell engager. It is given as an intravenous infusion and is indicated for the treatment of adults with relapsed or refractory follicular lymphoma after 2 or more lines of systemic therapy. Mosunetuzumab labeling has a boxed warning for cytokine release syndrome; severe neurologic toxicity has also been reported.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-For intravenous infusion use only.
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
-Mosunetuzumab is administered by a health care professional in a facility with medical personnel and equipment capable of managing severe reactions.
-Ensure patients are well hydrated and premedicate patients with a corticosteroid, H1-antihistamine (e.g., diphenhydramine), and acetaminophen prior to the mosunetuzumab infusion as recommended.
Dilution:
-Mosunetuzumab is available as single-dose 1-mg/mL or 30-mg/30 mL solution vials; further dilution is necessary before administration.
-Mosunetuzumab appears to be compatible with infusion bags made of polyvinyl chloride (PVC) or polyolefin (PO) such as polyethylene (PE) and polypropylene (PP).
-After determining the dose, total volume of the 1 mg/mL solution, and number of vials required, withdraw the required volume from the vial(s) using a sterile needle and syringe; discard any unused portion left in the vial.
-Withdraw an equal volume (as calculated above for the patient dose) from an infusion bag containing 0.9% Sodium Chloride Injection or 0.45% Sodium Chloride Injection (and discard) prior to injecting the required dose to make the IV infusion.
-Dilute the mosunetuzumab dose as follows:
--1-mg dose: Inject 1 mL of drug into 50 mL or 100 mL of diluent.
-2-mg dose: Inject 2 mL of drug into 50 mL or 100 mL of diluent.
-60-mg dose: Inject 60 mL of drug into 100 mL or 250 mL of diluent.
-30-mg dose: Inject 30 mL of drug into 50 mL, 100 mL, or 250 mL of diluent.
-Slowly invert the diluted admixture to mix; do not shake.
-Affix the peel-off label from the package insert to the infusion bag containing the diluted admixture.
-Storage: Administer the prepared IV infusion immediately (preferred) or store refrigerated at 2 to 8 degrees C (36 to 46 degrees F) for up to 24 hours or at an ambient temperature of 9 to 30 degrees C (48 to 86 degrees F) for up to 16 hours.
Intravenous (IV) infusion:
-If stored in the refrigerator, allow the diluted admixture to reach room temperature before administration.
-Mosunetuzumab appears to be compatible with infusion sets or aids that are made of PVC, PE, polyurethane (PUR), polybutadiene (PBD), silicone, acrylonitrile butadiene styrene (ABS), polycarbonate (PC), polyetherurethane (PEU), fluorinated ethylene propylene (FEP), or polytetrafluorethylene (PTFE).
-Administer IV as an infusion over a minimum of 4 hours for all doses (day 1, 8, and 15) given in cycle 1; if previous infusions from cycle 1 are well tolerated, administer subsequent doses (cycle 2 and beyond) IV over 2 hours.
-Do not use an in-line filter; however, drip chamber filters composed of polyamide (PA) may be used.
-Administer through a dedicated IV infusion line; do not mix in the same bag with other medicinal products.
Infection has been reported with mosunetuzumab therapy. Therapy interruption or permanent discontinuation may be necessary in patients who develop an infection. In a pooled safety analysis (n = 218), infections including opportunistic infections were reported in 17% (grade 3 or 4, 14%) of patients with hematologic malignancies who received mosunetuzumab; fatal infection occurred in 0.9% of patients. The most common grade 3 or higher infections were pneumonia, sepsis, and upper respiratory tract infection. Additionally, upper respiratory tract infection (14%; grade 3, 2.2%), urinary tract infection (10%; grade 3, 1.1%) including acute pyelonephritis, pneumonia (less than 10%), sepsis (less than 10%), COVID-19 infection(less than 10%), and Epstein-Barr viremia (less than 10%) occurred in patients with relapsed or refractory follicular lymphoma who received mosunetuzumab (n = 90) in a clinical study. Serious cases of pneumonia, sepsis, COVID-19 infection, and Epstein-Barr viremia were reported in 2% or more of patients. The term upper respiratory tract infection included naso-pharyngitis, sinusitis, and rhinovirus infection.
Myelosuppression has been reported with mosunetuzumab therapy. Provide supportive care per local institutional guidelines. Interruption or discontinuation of therapy may be necessary in patients who develop severe myelosuppression. Consider the prophylactic use of granulocyte colony-stimulating factors. In a pooled safety analysis (n = 218), grade 3 or 4 lymphopenia (92%), neutropenia (38%), leukopenia (22%), anemia (19%), thrombocytopenia (12%), and febrile neutropenia (2%) were reported in patients with hematologic malignancies who received mosunetuzumab. Additionally, decreased lymphocyte count/lymphopenia (100%; grade 3 or 4, 98%), decreased hemoglobin level/anemia (68%; grade 3 or 4, 12%), decreased white blood cell count/leukopenia (60%; grade 3 or 4, 13%), decreased neutrophil count/neutropenia (58%; grade 3 or 4, 40%), and decreased platelets count/thrombocytopenia (46%; grade 3 or 4, 10%) that worsened from baseline occurred in patients with relapsed or refractory follicular lymphoma who received mosunetuzumab (n = 90) in a clinical study.
In a pooled safety analysis (n = 218), tumor flare was reported in 4% of patients with hematologic malignancies who received mosunetuzumab. Signs and symptoms of tumor flare may include new or worsening pleural effusion, localized pain and swelling of lymphoma lesions, and tumor inflammation. Monitor patients with bulky tumors or disease located closely to airways or a vital organ closely during initial therapy. Also observe patients for signs of compression or obstruction due to mass effect secondary to tumor flare; institute standard treatment if these conditions occur. Tumor flare occurred in less than 10% of patients with relapsed or refractory follicular lymphoma who received mosunetuzumab (n = 90) in a clinical study; serious tumor flare events were reported in 2% or more of patients.
In a pooled safety analysis (n = 218), fatigue was reported in 36% of patients with hematologic malignancies who received mosunetuzumab. Additionally, fatigue including asthenia and lethargy occurred in 42% of patients with relapsed or refractory follicular lymphoma who received mosunetuzumab (n = 90) in a clinical study.
In a pooled safety analysis (n = 218), fever was reported in 24% of patients with hematologic malignancies who received mosunetuzumab. Additionally, fever (29%; grade 3, 1.1%) and chills (13%; grade 3, 1.1%) occurred in patients with relapsed or refractory follicular lymphoma who received mosunetuzumab (n = 90) in a clinical study.
Edema occurred in 17% (grade 3 or 4, 1.1%) of patients with relapsed or refractory follicular lymphoma who received mosunetuzumab (n = 90) in a clinical study. The term edema included peripheral edema or swelling, face edema or swelling, pulmonary edema, and fluid retention or overload.
In a pooled safety analysis (n = 218), rash was reported in 34% of patients with hematologic malignancies who received mosunetuzumab. Additionally, rash (39%; grade 3, 4.4%), pruritus (21%), xerosis/dry skin (16%), and skin exfoliation (10%) occurred in patients with relapsed or refractory follicular lymphoma who received mosunetuzumab (n = 90) in a clinical study. The term rash included erythema, palmar erythema, erythematous rash, exfoliative dermatitis/rash, maculopapular rash, pustular rash, and acneiform rash/dermatitis.
Musculoskeletal pain (28%; grade 3, 1.1%) and arthralgia (11%) occurred in patients with relapsed or refractory follicular lymphoma who received mosunetuzumab (n = 90) in a clinical study. The musculoskeletal pain term included back pain, myalgia, musculoskeletal chest pain, and neck pain.
Cough (22%) including upper airway cough syndrome and dyspnea (11%; grade 3, 1.1%) occurred in patients with relapsed or refractory follicular lymphoma who received mosunetuzumab (n = 90) in a clinical study.
Cytokine release syndrome (CRS) has been reported with mosunetuzumab therapy. Common symptoms include fever, chills, hypotension, sinus tachycardia, hypoxia, and headache. Continue premedications with subsequent mosunetuzumab doses in patients who experienced CRS after a prior dose. Interruption or discontinuation of therapy may be necessary in patients who develop CRS; evaluate the need for hospitalization, supportive care, and further management (using current practice guideline) in patients with severe CRS. In a pooled safety analysis (n = 218), CRS was reported in 39% (grade 3, 2%; grade 4, 0.5%) of patients with hematologic malignancies who received mosunetuzumab; recurrent CRS occurred in 11% of patients. CRS developed most frequently following doses in cycle 1; the median duration of CRS in all cycles was 3 (range, 1 to 29) days. CRS occurred in 44% (grade 3 or 4, 2.2%) of patients with relapsed or refractory follicular lymphoma who received mosunetuzumab (n = 90) in a clinical study.
Neurotoxicity including immune effector cell-associated neurotoxicity syndrome (ICANS) has been reported with mosunetuzumab therapy. Neurotoxicity may occur concurrently with cytokine release syndrome. Consider a neurology consultation for further evaluation and management in any patient with tremors, dizziness, insomnia, severe neurotoxicity, or any other adverse reactions that impair consciousness. Interruption or discontinuation of therapy may be necessary in patients who develop neurotoxicity; evaluate the need for supportive care and further management (using current practice guideline) in patients with severe neurotoxicity or ICANS. In a pooled safety analysis (n = 218), neurotoxicity (39%; grade 3, 3%) including headache (21%), peripheral neuropathy (13%), dizziness (11%), mental status changes (6%), and ICANS (1%) were reported in patients with hematologic malignancies who received mosunetuzumab. The term mental status changes included confusion, disturbance in attention, cognitive disorder/impaired cognition, delirium, encephalopathy, and somnolence/drowsiness. Headache (32%; grade 3, 1.1%) including migraine, peripheral neuropathy (20%), and dizziness (12%) including vertigo, mental status changes (less than 10%), and motor dysfunction (less than 10%) including ataxia, gait disturbance, and tremor occurred in patients with relapsed or refractory follicular lymphoma who received mosunetuzumab (n = 90) in a clinical study. The term peripheral neuropathy included paresthesias, dysesthesia, hypoesthesia, burning sensation, and neuralgia. Psychiatric adverse events included insomnia (12%) and anxiety (less than 10%) in this same clinical study.
Diarrhea (17%), nausea (17%), and abdominal pain (12%; grade 3, 1.1%) occurred in patients with relapsed or refractory follicular lymphoma who received mosunetuzumab (n = 90) in a clinical study.
In a pooled safety analysis (n = 218), grade 3 or 4 hyperuricemia was reported 15% of patients with hematologic malignancies who received mosunetuzumab. Additionally, increased uric acid level/hyperuricemia that worsened from baseline (grade 3 or 4, 22%) and tumor lysis syndrome (TLS) (less than 10%) occurred in patients with relapsed or refractory follicular lymphoma who received mosunetuzumab (n = 90) in a clinical study. TLS can lead to serious events such as acute renal failure and cardiac arrhythmia. Renal insufficiency occurred in less than 10% of patients with relapsed or refractory follicular lymphoma who received mosunetuzumab (n = 90) in a clinical study; serious renal insufficiency was reported in 2% or more of patients.
In a pooled safety analysis (n = 218), grade 3 or 4 hypophosphatemia was reported 41% of patients with hematologic malignancies who received mosunetuzumab. Additionally, decreased phosphate level/hypophosphatemia (78%; grade 3 or 4, 46%), decreased magnesium level/hypomagnesemia (34%), and decreased potassium level/hypokalemia (33%; grade 3 or 4, 6%) that worsened from baseline occurred in patients with relapsed or refractory follicular lymphoma who received mosunetuzumab (n = 90) in a clinical study.
In a pooled safety analysis (n = 218), grade 3 or 4 hyperglycemia was reported 40% of patients with hematologic malignancies who received mosunetuzumab. Additionally, grade 3 or 4 increased glucose level/hyperglycemia that worsened from baseline occurred in 42% of patients with relapsed or refractory follicular lymphoma who received mosunetuzumab (n = 90) in a clinical study.
Elevated hepatic enzymes including increased AST (39%; grade 3 or 4, 4.4%), ALT (32%; grade 3 or 4, 7%), and gamma-glutamyl transferase (34%; grade 3 or 4, 9%) levels that worsened from baseline occurred in patients with relapsed or refractory follicular lymphoma who received mosunetuzumab (n = 90) in a clinical study.
In 67 patients who had immunoglobulin (IgG) levels of 500 mg/dL or more at baseline, hypogammaglobulinemia (defined as IgG levels less than 500 mg/dL) was reported in 40% of patients after receiving mosunetuzumab.
Cytokine release syndrome (CRS) has been reported with mosunetuzumab use; some cases were serious or life-threatening. Monitor patients for signs or symptoms of CRS such as fever, chills, hypotension, tachycardia, hypoxia, and headache during treatment. Evaluate for and treat other causes of fever, hypoxia, and hypotension. To reduce the risk of CRS, ensure adequate hydration, administer mosunetuzumab according to a step-up dosing schedule, and give premedications prior to each dose in cycles 1 and 2 as follows: dexamethasone 20 mg IV or methylprednisolone 80 mg IV (complete at least 1 hour prior to the infusion) and diphenhydramine 50 to 100 mg (or equivalent) PO/IV and acetaminophen 500 to 1,000 mg PO at least 30 minutes prior to the infusion. Continue premedications with subsequent mosunetuzumab doses in patients who experienced CRS after a prior dose. Interruption or discontinuation of therapy may be necessary in patients who develop CRS; evaluate the need for hospitalization, supportive care, and further management (using current practice guideline) in patients with severe CRS.
Neurotoxicity including immune effector cell-associated neurotoxicity syndrome (ICANS) has been reported with mosunetuzumab therapy. Use mosunetuzumab with caution with other medications or substances that cause dizziness or mental status changes. Monitor patients for signs or symptoms of neurologic toxicity such as tremors, dizziness, insomnia, and impaired consciousness during treatment; consider a neurology consultation for further evaluation and management. Rule out other causes of neurologic symptoms. Neurotoxicity may occur concurrently with cytokine release syndrome. Interruption or discontinuation of therapy may be necessary in patients who develop neurotoxicity; evaluate the need for supportive care and further management (using current practice guideline) in patients with severe neurotoxicity or ICANS.
Advise patients who experience cytokine release syndrome, neurotoxicity, or other adverse reactions that impair consciousness during mosunetuzumab therapy to refrain from driving or operating machinery until the toxicity resolves.
Because of the risk of tumor flare, cytokine release syndrome, and neurological toxicities, use requires an experienced clinician with training in the management of these toxicities. Mosunetuzumab administration also requires a specialized care setting that has equipment capable of managing severe reactions. Patients with bulky tumors or disease located in proximity to airways or a vital organ should be monitored closely during initial therapy since serious/severe tumor flare may develop. 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.
Severe infections have been reported with mosunetuzumab therapy; some cases were fatal or life-threatening. Do not administer mosunetuzumab therapy in patients who have an active infection. Administer prophylactic antibiotics as recommended according to clinical guidelines. Monitor patients for signs and symptoms of infection prior to and during mosunetuzumab therapy; treat appropriately. Therapy interruption or permanent discontinuation may be necessary in patients who develop an infection. Use mosunetuzumab with caution in patients with a history of recurring or chronic infection (e.g., Epstein-Barr virus), with underlying conditions that may predispose them to getting infections, or who have had significant prior immunosuppression treatment.
Hematologic toxicity (e.g., anemia, neutropenia, febrile neutropenia, and thrombocytopenia) has been reported with mosunetuzumab therapy. Evaluate complete blood cell counts during treatment; provide supportive care per local institutional guidelines. Interruption or discontinuation of therapy may be necessary in patients who develop severe myelosuppression. Consider the prophylactic use of granulocyte colony-stimulating factors.
Mosunetuzumab may cause fetal harm if administered during pregnancy based on its mechanism of action. Pregnant patients should be apprised of the potential hazard to the fetus. There are no available data with mosunetuzumab use during human pregnancy; animal reproductive and developmental toxicity studies have not been conducted. Mosunetuzumab causes T-cell activation and cytokine release; immune activation may compromise pregnancy maintenance. Human immunoglobulin (IgG) is known to cross into the placenta; therefore, mosunetuzumab may be transmitted from the mother to the developing fetus. It may also cause B-cell depletion and lymphocytopenia in neonates and infants exposed to mosunetuzumab in-utero.
Counsel patients about the reproductive risk and contraception requirements during mosunetuzumab treatment. Pregnancy testing should be performed prior to starting mosunetuzumab in females of reproductive potential. These patients should use effective contraception during and for 3 months after the last mosunetuzumab dose.
There is no information regarding the presence of mosunetuzumab 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 absorption leading to B-cell depletion in the breastfed child, advise patients to avoid breast-feeding during treatment and for 3 months after the last dose.
For the treatment of non-Hodgkin's lymphoma (NHL):
-for the treatment of relapsed or refractory follicular lymphoma after 2 or more lines of systemic therapy:
NOTE: The FDA has designated mosunetuzumab as an orphan drug for the treatment of follicular lymphoma.
Intravenous dosage:
Adults: Cycle 1: 1 mg IV infusion on day 1; give 2 mg IV infusion on day 8, and 60 mg IV infusion on day 15. Cycle 2: 60 mg IV infusion on day 1. Cycle 3 and beyond: 30 mg IV infusion on day 1, then repeat every 21 days until disease progression or for 8 cycles. In those achieving a complete response, stop treatment after 8 cycles. In those who have a partial response or stable disease, treatment may extend beyond 8 cycles up to a maximum of 17 cycles. Therapy interruption or discontinuation may be necessary in those who develop toxicity. Ensure adequate hydration prior to IV infusion. Premedicate before each dose in Cycles 1 and 2 as follows: dexamethasone 20 mg IV or methylprednisolone 80 mg IV (complete at least 1 hour prior to the infusion) and diphenhydramine 50 to 100 mg (or equivalent) PO/IV and acetaminophen 500 to 1,000 mg PO at least 30 minutes before infusion. Continue premedication with subsequent IV infusion doses in those who experience cytokine release syndrome with a prior dose. At a median follow-up of 18.3 months, the independent review committee-assessed complete response rate was 60% in patients who had relapsed or refractory follicular lymphoma who received mosunetuzumab in a multicenter, single-arm, phase 2 trial (n = 90). Additionally, 80% of patients achieved an objective response. The median time to and duration of response was 1.4 (range, 1.1 to 8.9) months and 22.8 (95% CI, 9.7 to not reached) months, respectively; the median progression-free survival time was 17.9 months. In this study, patients (median age, 60 [range, 29 to 90] years; bulky disease, 34%) had received a median of 3 (range, 2 to 10) prior therapies and all had received prior therapy with an alkylator and an anti-CD20 agent; 21% of patients had previously received an autologous stem-cell transplantation.
Therapeutic Drug Monitoring:
Recommendations for Restarting Therapy After Dose Delay
Cycle 1
Day 1, 1 mg: For a delay of 1 to 2 weeks, give the cycle 1, day 8 dose of 2 mg and then resume the planned treatment schedule. For a delay of more than 2 weeks, repeat the cycle 1, day 1 dose of 1 mg and then resume the planned treatment schedule.
Day 8, 2 mg: For a delay of 1 to 2 weeks, give the cycle 1, day 15 dose of 60 mg and then resume the planned treatment schedule. For a delay of more than 2 weeks but less than 6 weeks, repeat the cycle 1, day 8 dose of 2 mg and then resume the planned treatment schedule. For a delay of more than 6 weeks, repeat the cycle 1, day 1 dose of 1 mg and then resume the planned treatment schedule.
Day 15, 60 mg: For a delay of 1 week to less than 6 weeks, give the cycle 2, day 1 dose of 60 mg and then resume the planned treatment schedule. For a delay of 6 weeks or more, start cycle 2 as follows: day 1, give 1 mg; day 8, give 2 mg; day 15, give 60 mg and then resume the planned treatment schedule on cycle 3.
Cycle 2
Day 1, 60 mg: For a delay of 3 weeks to less than 6 weeks, give the cycle 3, day 1 dose of 30 mg and then resume the planned treatment schedule. For a delay of 6 weeks or more, start cycle 3 as follows: day 1, give 1 mg; day 8, give 2 mg; day 15, give 30 mg and then resume the planned treatment schedule on cycle 4.
Cycle 3 and Subsequent Cycles
Day 1, 30 mg: For a delay of 3 weeks to less than 6 weeks, give 30 mg and then resume the planned treatment schedule. For a delay of 6 weeks, start the next cycle as follows: day 1, give 1 mg; day 8, give 2 mg; day 15, give 30 mg and then resume the planned treatment schedule on subsequent cycles.
Management of Treatment-Related Toxicity
Cytokine Release Syndrome (CRS) NOTE: Fever may be masked by premedications; follow these management guidelines if the clinical presentation is consistent with CRS.
Grade 1 toxicity (temperature of 38 degrees C [100.4 degrees F] or more attributed to CRS): Hold the mosunetuzumab infusion until symptoms resolve; resume therapy at the same infusion rate. Ensure that CRS symptoms are resolved for at least 72 hours prior to giving the next dose. Administer premedications prior to next dose and monitor patients more frequently.
Grade 2 toxicity (temperature of 38 degrees C [100.4 degrees F] or more attributed to CRS with the following: hypotension not requiring vasopressors and/or oxygen requirement of low-flow [6 L or less] nasal cannula or blow-by): Hold the mosunetuzumab infusion until symptoms resolve and provide symptomatic management using current practice guidelines; resume therapy at 50% of the infusion rate. Ensure that CRS symptoms are resolved for at least 72 hours prior to giving the next dose. Administer premedications prior to next dose and consider infusing that dose at 50% of the infusion rate. Monitor patients more frequently with the next dose and consider hospitalization. For recurrent grade 2 toxicity, manage per grade 3 CRS toxicity.
Grade 3 toxicity (temperature of 38 degrees C [100.4 degrees F] or more attributed to CRS with the following: hypotension requiring a vasopressor with or without vasopressin and/or oxygen requirement of high-flow [more than 6 L] nasal cannula, facemask, non-rebreather mask, or Venturi mask): Hold mosunetuzumab, start symptomatic management using current practice guidelines, and provide supportive care which may include intensive care. Ensure that CRS symptoms are resolved for at least 72 hours prior to giving the next dose. Administer the next dose in the hospital; give premedications and infuse the dose at 50% of the infusion rate. For recurrent grade 3 toxicity, permanently discontinue mosunetuzumab.
Grade 4 toxicity (temperature of 38 degrees C [100.4 degrees F] or more attributed to CRS with the following: hypotension requiring multiple vasopressors (excluding vasopressin) and/or oxygen requirement of positive pressure [e.g., continuous positive airway pressure, bilevel positive airway pressure, intubation, and mechanical ventilation]): Permanently discontinue mosunetuzumab, start symptomatic management using current practice guidelines, and provide supportive care which may include intensive care.
Neurologic Toxicity Including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)
NOTE: Manage grade 2 or greater ICANS per current practice guidelines. Severity based on American Society for Transplantation and Cellular Therapy (ASTCT) 2019 grading for ICANS.
Grade 2 toxicity: Hold mosunetuzumab until neurotoxicity symptoms improve to grade 1 or baseline for at least 72 hours. Provide supportive care as necessary.
Grade 3 toxicity: For first occurrence, hold mosunetuzumab until neurotoxicity symptoms improve to grade 1 or baseline for at least 72 hours. Provide supportive care which may include intensive care and consider a neurology consultation. For recurrence, permanently discontinue mosunetuzumab.
Grade 4 toxicity: Permanently discontinue mosunetuzumab. Provide supportive care which may include intensive care and consider a neurology consultation.
Neutropenia
Absolute neutrophil count (ANC) less than 0.5 x 109 cells/L: Hold mosunetuzumab until the ANC is 0.5 x 109 cells/L or more.
Infection
Any grade toxicity: Hold mosunetuzumab in patients with active infection until the infection resolves.
Grade 4 toxicity: Consider permanently discontinuing mosunetuzumab.
Other Toxicity
Grade 3 or 4 toxicity: Hold mosunetuzumab until the toxicity improves to grade 1 or baseline.
Maximum Dosage Limits:
-Adults
60 mg IV infusion.
-Geriatric
60 mg IV infusion.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no initial dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no initial dosage adjustments are needed.
*non-FDA-approved indication
Monitor for toxicity and adjust doses as needed for CYP substrates, especially during the first 2 weeks of each mosunetuzumab cycle and during and after cytokine release syndrome. Mosunetuzumab causes cytokine release that may alter CYP enzyme activity.
Mosunetuzumab is a bispecific T-cell engaging (BiTE) monoclonal antibody that binds to CD20 expressed on lymphoma cells and CD3 expressed on the surface of T-cells. It is a humanized immunoglobulin G1 (IgG1) antibody produced from Chinese Hamster Ovary cells using recombinant DNA technology. The binding of T-cells to lymphoma cells triggers a signaling cascade leading to the release of pro-inflammatory cytokines and proliferation of T-cells ultimately resulting in the lysis of CD20-positive B-cells.
Mosunetuzumab is administered intravenously (IV). It has a mean volume of distribution of 5.49 L (coefficient of variation (CV), 31%), a steady-state geometric mean terminal elimination half-life of 16.1 days (CV, 17.3%), and a geometric mean clearance at steady state of 0.584 L/day (CV, 18%). Following the recommended dosage of IV mosunetuzumab, peripheral B-cell counts decreased to undetectable levels in 92% of patients by day 1 of cycle 2; this depletion was sustained at cycles 4 and 8. A transient elevation of cytokines (IL-2, IL-6, IL-10, TNF-alpha, and IFN-gamma) occurred at doses of 0.4 mg or more. Peak cytokine levels were observed in the first cycle within 24 hours after the day 1 (1 mg) and day 15 (60 mg) mosunetuzumab doses; cytokine levels returned to baseline prior to the next infusion.
Affected cytochrome P450 isoenzymes and drug transporters: CYP substrates
Mosunetuzumab may cause a cytokine release that suppresses CYP enzyme activity and which may increase the exposure of CYP substrates. No clinical studies evaluating the drug interaction potential of mosunetuzumab have been conducted. Increased exposure of CYP450 substrates is more likely to occur after the first dose of Cycle 1 and for up to 14 days after the second 60 mg dose of Cycle 2, or if a cytokine release syndrome (CRS) occurs during treatment. Monitor and adjust concomitantly administered narrow therapeutic index drugs when indicated or suggested by the prescribing label for such medications.
-Route-Specific Pharmacokinetics
Intravenous Route
The pharmacokinetic parameters of mosunetuzumab increase proportionally over a dosage range of 0.2 to 60 mg (0.007 to 2 times the recommended treatment dosage). At steady state (achieved by cycle 4 at approximately 63 to 84 days after the first dose), the mosunetuzumab geometric mean Cmax and AUC values were 7.02 mcg/mL (coefficient of variation (CV), 37.9%) and 52.9 mcg x day/mL (CV, 40.7%), respectively.
-Special Populations
Mild hepatic impairment (total bilirubin level less than or equal to the ULN with AST level more than the ULN OR a total bilirubin level more than 1 to 1.5 times the ULN with any AST level) does not significantly impact the pharmacokinetic (PK) parameters of mosunetuzumab. The effect of moderate to severe hepatic impairment (total bilirubin level more than 1.5 times ULN with any AST level) on the PK parameters of mosunetuzumab is unknown.
Renal Impairment
Mild or moderate renal impairment [estimated creatinine clearance (CrCl) of 30 to 89 mL/minute, using the Cockcroft-Gault formula] does not significantly impact the pharmacokinetic parameters of mosunetuzumab. The effect of severe renal impairment (CrCl 15 to 29 mL/minute) on the pharmacokinetic parameters of mosunetuzumab is unknown.
Geriatric
Age (range, 19 to 96 years) does not significantly impact the pharmacokinetic parameters of mosunetuzumab.
Gender Differences
Sex does not significantly impact the pharmacokinetic parameters of mosunetuzumab.
Ethnic Differences
Race (Asian and Non-Asian) or ethnicity (Hispanic/Latino or not Hispanic/Latino) does not significantly impact the pharmacokinetic parameters of mosunetuzumab.