Mosunetuzumab-axgb, a bispecific CD20-directed CD3 T-cell engager, is an antineoplastic agent.1
Mosunetuzumab-axgb is used for the treatment of relapsed or refractory follicular lymphoma in adults who previously received ≥2 lines of systemic therapy.1, 2 Mosunetuzumab-axgb is designated an orphan drug by FDA for the treatment of this cancer.3 The current indication is approved under accelerated approval based on response rate; continued FDA approval for this indication may be contingent on verification and description of clinical benefit in a confirmatory trial.1
The current indication for mosunetuzumab-axgb is based principally on the results of a multicenter, single-arm, open-label, phase 2 study (NCT02500407) in 90 adults with relapsed or refractory follicular lymphoma who previously received ≥2 lines of treatment, including an anti-CD20 monoclonal antibody and an alkylating agent.1, 2 In this study, patients received IV mosunetuzumab-axgb in 21-day cycles with step-up dosing as follows: 1 mg on cycle 1 day 1, 2 mg on cycle 1 day 8, 60 mg on cycle 1 day 15 and cycle 2 day 1, and 30 mg on day 1 of cycle 3 and subsequent cycles.1, 2 Mosunetuzumab-axgb was administered for 8 cycles unless patients experienced disease progression or unacceptable toxicity.1 After 8 cycles, patients who achieved a complete response discontinued therapy; patients with a partial response or stable disease continued treatment for up to 17 cycles, unless they experienced disease progression or unacceptable toxicity.1
The median age of patients in this study was 60 years; 61% were male, 82% were white, 77% had stage III or IV disease, 34% had bulky disease, and all patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.1, 2 The median number of prior lines of therapy was 3, with 38% of patients receiving 2 prior lines, 31% receiving 3 prior lines, and 31% receiving more than 3 prior lines.1, 2 Seventy-nine percent of patients were refractory to previous anti-CD20 therapy, 53% were refractory to previous anti-CD20 therapy and an alkylator therapy, and 21% had previous autologous stem cell transplant.1, 2 Fifty-two percent of patients had progression of disease within 24 months from the start of initial systemic therapy.1, 2
In this study, efficacy was established based on objective response rate (complete or partial response) and duration of response (DOR) as assessed by an independent review committee; DOR was defined as the time from initial occurrence of a partial or complete response to first disease progression or death from any cause in patients who achieved a partial or complete response.1, 2 The median follow-up for DOR was 14.9 months.1 At the time of data analysis, according to independent review committee assessment, an objective response was recorded in 80% of patients, with a complete response observed in 60% of patients, and a partial response observed in 20%.1, 2 The median DOR was 22.8 months and the 12- and 18-month continued response rates were approximately 62% and 57%, respectively.1, 2 The median time to first response was 1.4 months;1, 2 median overall survival was not reached at the time of analysis.2
Follicular lymphoma is the most common type of indolent non-Hodgkin lymphoma.4 This type of lymphoma may resolve without treatment; however, treatment is required if signs or symptoms reappear after the cancer has resolved or after initial cancer treatment.4 Watchful waiting is the standard of care during the initial encounter and for patients with slow asymptomatic relapsing follicular lymphoma.5 When treatment is required, several therapeutic options may be used in varying sequences, such as rituximab alone or in combination with chemotherapy, rituximab in combination with lenalidomide, and obinutuzumab alone or in combination with chemotherapy.5 CD19-directed chimeric antigen receptor T cells may be used in patients who have disease progression after ≥2 prior lines of therapy.5 Mosunetuzumab-axgb may also be used in patients with relapsed or refractory follicular lymphoma with disease progression after ≥2 prior lines of therapy.5
Mosunetuzumab-axgb is administered via IV infusion only; it is supplied in single-dose vials containing mosunetuzumab-axgb 1 mg/mL solution and requires further dilution prior to administration.1
Mosunetuzumab-axgb should only be administered by a qualified healthcare professional with appropriate medical support to manage severe reactions such as CRS and neurologic toxicity.1
Store unopened vials of mosunetuzumab-axgb at 2-8ºC in the original carton to protect from light; do not freeze or shake.1
Administer mosunetuzumab-axgb through a dedicated infusion line; do not use an in-line filter.1 Drip chamber filters may be used to administer mosunetuzumab-axgb.1
Determine the dose, the total volume of mosunetuzumab-axgb solution required, and the number of vials needed.1 Obtain an infusion bag containing 0.9% sodium chloride or 0.45% sodium chloride injection; withdraw a volume of solution equal to the volume of mosunetuzumab-axgb required for the patient's dose and discard.1 Only use infusion bags made of polyvinyl chloride (PVC) or polyolefin such as polyethylene and polypropylene.1
Withdraw the required volume of mosunetuzumab-axgb from the vial using a sterile needle and syringe and dilute into the infusion bag containing 0.9% sodium chloride or 0.45% sodium chloride injection as noted in Table 1.1 Discard any unused portion left in the vial.1
Dose | Volume of Mosunetuzumab-axgb in 0.9% or 0.45% Sodium Chloride Solution | Size of Infusion Bag |
|---|---|---|
1 mg | 1 mL | 50 mL or 100 mL |
2 mg | 2 mL | 50 mL or 100 mL |
60 mg | 60 mL | 100 mL or 250 mL |
30 mg | 30 mL | 50 mL, 100 mL, or 250 mL |
Gently mix by slowing inverting the IV bag.1 Do not shake.1
Apply the peel-off label from the package insert to the infusion bag.1
Immediately use the diluted solution.1 If not used immediately, the diluted solution can be stored refrigerated at 2-8°C for up to 24 hours and at ambient temperature 9-30°C for up to 16 hours.1 Prior to administration, ensure the infusion solution comes to room temperature.1
Infusions should be administered over a minimum of 4 hours during cycle 1.1 If infusions during cycle 1 are well-tolerated, infusions in subsequent treatment cycles may be administered over 2 hours.1
Premedication is recommended to prevent CRS and infusion-related reactions; specific recommendations for premedication are summarized in Table 2.1
Treatment Cycle | Patients Requiring Premedication | Premedication | Dosage | Administration |
|---|---|---|---|---|
Cycle 1 and Cycle 2 | All patients | Corticosteroid | Dexamethasone 20 mg IV or methylprednisolone 80 mg IV | Complete at least 1 hour prior to infusion |
Cycle 1 and Cycle 2 | All patients | Antihistamine | Diphenhydramine 50-100 mg or equivalent oral or IV antihistamine | At least 30 minutes prior to infusion |
Cycle 1 and Cycle 2 | All patients | Antipyretic | Oral acetaminophen (500-1000 mg) | At least 30 minutes prior to infusion |
Cycles 3+ | Patients who experienced any grade CRS with the previous dose | Corticosteroid | Dexamethasone 20 mg IV or methylprednisolone 80 mg IV | Complete at least 1 hour prior to infusion |
Cycles 3+ | Patients who experienced any grade CRS with the previous dose | Antihistamine | Diphenhydramine 50-100 mg or equivalent oral or IV antihistamine | At least 30 minutes prior to infusion |
Cycles 3+ | Patients who experienced any grade CRS with the previous dose | Antipyretic | Oral acetaminophen (500-1000 mg) | At least 30 minutes prior to infusion |
The recommended dosage of mosunetuzumab-axgb in adults with relapsed or refractory follicular lymphoma is shown in Table 3.1 The usual duration is 8 cycles, unless patients experience unacceptable toxicity or disease progression.1 Treatment beyond 8 cycles is not required for patients who achieve a complete response.1 Administer an additional 9 cycles of treatment in patients who achieve a partial response or have stable disease after the initial 8 cycles, unless the patient experiences unacceptable toxicity or disease progression.1
Treatment Cycle | Day of Treatment | Dose of Mosunetuzumab-axgb | Rate of Infusion |
|---|---|---|---|
Cycle 1 | Day 1 | 1 mg | Administer over a minimum of 4 hours |
Cycle 1 | Day 8 | 2 mg | Administer over a minimum of 4 hours |
Cycle 1 | Day 15 | 60 mg | Administer over a minimum of 4 hours |
Cycle 2 | Day 1 | 60 mg | Administer over 2 hours if infusions from Cycle 1 were well tolerated |
Cycle 3+ | Day 1 | 30 mg | Administer over 2 hours if infusions from Cycle 1 were well tolerated |
Dosage Modification for Toxicity
Patients who experience CRS, neurologic toxicity, or other adverse reactions may require dosage adjustment, dose delay, or treatment discontinuation, depending on severity.1 Recommendations for the management of CRS, neurologic toxicity, and other adverse reactions are summarized in Tables 4, 5, and 6, respectively.1 If restarting mosunetuzumab-axgb after a dose delay, follow dosage recommendations in Table 7.1
Identify CRS based on clinical presentation.1 Evaluate for and treat other causes of fever, hypoxia, and hypotension.1 If CRS is suspected, hold mosunetuzumab-axgb until CRS resolves and manage according to recommendations in Table 4.1 Administer supportive therapy for CRS, including intensive care if warranted.1 If CRS is refractory to management, consider other causes, including hemophagocytic lymphohistiocytosis.1
Severity | Presenting Symptoms | Actions |
|---|---|---|
Grade 1 | Fever ≥38°Ca | Withhold infusion and manage per current practice guidelines; if symptoms resolve, restart infusion at the same rate. Ensure CRS symptoms are resolved for at least 72 hours prior to the next dose.b Administer premedication prior to next dose and monitor more frequently. |
Grade 2 | Fever ≥38°Ca with hypotension not requiring vasopressors and/or hypoxia requiring low-flow oxygen by nasal cannula or blow-byc | Withhold infusion and manage per current practice guidelines; if symptoms resolve, restart infusion at 50% rate. Ensure CRS symptoms are resolved for at least 72 hours prior to the next dose.b Administer premedication prior to next dose and consider infusing the next dose at 50% rate. For the next dose, monitor more frequently and consider hospitalization. For recurrent Grade 2 CRS, manage as Grade 3 CRS. |
Grade 3 | Fever ≥38°Ca with hypotension requiring a vasopressor (with or without vasopressin) and/or hypoxia requiring high-flow oxygen by nasal cannula, face mask, non-rebreather mask, or Venturi maskc | Withhold infusion, manage per current guidelines, and provide supportive therapy, which may include intensive care. Ensure CRS symptoms are resolved for at least 72 hours prior to the next dose.b Administer premedication prior to next dose and infuse the next dose at 50% rate. Hospitalize for the next dose. For recurrent Grade 3 CRS, permanently discontinue. Manage CRS per current practice guidelines and provide supportive therapy, which may include intensive care. |
Grade 4 | Fever ≥38°Ca with hypotension requiring multiple vasopressors (excluding vasopressin) and/or hypoxia requiring oxygen by positive pressure (e.g., CPAP, BiPAP, intubation and mechanical ventilation) | Permanently discontinue. Manage CRS per current practice guidelines and provide supportive therapy, which may include intensive care. |
aPremedication may mask fever; if clinical presentation is consistent with CRS, follow these management guidelines.
bRefer to Table 7 for information on restarting after dose delays.
cLow-flow oxygen defined as oxygen delivered at <6 L/min; high-flow oxygen defined as oxygen delivered at ≥6 L/min.
At the first sign of neurologic toxicity, including ICANS, hold mosunetuzumab-axgb and consider neurology evaluation.1 Manage as recommended in Table 5.1 Rule out other causes of neurologic symptoms.1 Provide supportive therapy, which may include intensive care. 1
Severity | Actions |
|---|---|
Grade 2 | Withhold until neurologic toxicity symptoms improve to Grade 1 or baseline for at least 72 hours.a Provide supportive therapy. If ICANS, manage per current practice guidelines. |
Grade 3 | Withhold until neurologic toxicity symptoms improve to Grade 1 or baseline for at least 72 hours.a Provide supportive therapy, which may include intensive care, and consider neurology evaluation. If ICANS, manage per current practice guidelines. If recurrence, permanently discontinue. |
Grade 4 | Permanently discontinue. Provide supportive therapy, which may include intensive care, and consider neurology evaluation. If ICANS, manage per current practice guidelines. |
aRefer to Table 7 for information on restarting after dose delays.
Adverse events other than CRS or neurologic toxicity should be managed as recommended in Table 6.1
Adverse Reaction | Severity | Actions |
|---|---|---|
Infections | Grades 1-4 | Withhold in patients with active infection until the infection resolves.a For Grade 4 infection, consider permanent discontinuation. |
Neutropenia | Absolute neutrophil count <500 cells/mma | Withhold until absolute neutrophil count is ≥500 cells/mm.a |
Other Adverse Reactions | Grade 3 or higher | Withhold until the toxicity resolves to Grade 1 or baseline.a |
aRefer to Table 7 for information on restarting after dose delays.
Table 7 provides recommendations on restarting therapy after a dose delay due to toxicity.1
Last Dose Administered | Time Since Last Dose | Action for Next Dose |
|---|---|---|
1 mg Cycle 1 Day 1 | 1-2 weeks | Administer 2 mg (Cycle 1 Day 8), then resume the planned treatment schedule |
1 mg Cycle 1 Day 1 | >2 weeks | Repeat 1 mg (Cycle 1 Day 1), then administer 2 mg (Cycle 1 Day 8) and resume the planned treatment schedule |
2 mg Cycle 1 Day 8 | 1-2 weeks | Administer 60 mg (Cycle 1 Day 15), then resume the planned treatment schedule |
2 mg Cycle 1 Day 8 | >2 weeks and <6 weeks | Repeat 2 mg (Cycle 1 Day 8), then administer 60 mg (Cycle 1 Day 15) and resume the planned treatment schedule |
2 mg Cycle 1 Day 8 | ≥6 weeks | Repeat 1 mg (Cycle 1 Day 1) and 2 mg (Cycle 1 Day 8), then administer 60 mg (Cycle 1 Day 15) and resume the planned treatment schedule |
60 mg Cycle 1 Day 15 | 1 week to <6 weeks | Administer 60 mg (Cycle 2 Day 1), then resume the planned treatment schedule |
60 mg Cycle 1 Day 15 | ≥6 weeks | Repeat 1 mg (Cycle 2 Day 1) and 2 mg (Cycle 2 Day 8), then administer 60 mg (Cycle 2 Day 15), followed by 30 mg (Cycle 3 Day 1) and resume the planned treatment schedule |
60 mg Cycle 2 Day 1 | 3 weeks to <6 weeks | Administer 30 mg (Cycle 3 Day 1), then resume the planned treatment schedule |
60 mg Cycle 2 Day 1 | ≥6 weeks | Repeat 1 mg (Cycle 3 Day 1) and 2 mg (Cycle 3 Day 8), then administer 30 mg (Cycle 3 Day 15)a, followed by 30 mg (Cycle 4 Day 1) and resume the planned treatment schedule |
30 mg Cycle 3 onwards | 3 weeks to <6 weeks | Administer 30 mg, then resume the planned treatment schedule |
30 mg Cycle 3 onwards | ≥6 weeks | Repeat 1 mg on Day 1 and 2 mg on Day 8 during the next cycle, then administer 30 mg on Day 15a, followed by 30 mg on Day 1 of subsequent cycles |
aFor the Day 1, Day 8, and Day 15 doses in the next cycle, administer premedication for all patients.
The manufacturer makes no specific dosage recommendations for patients with hepatic impairment.1
The manufacturer makes no specific dosage recommendations for patients with renal impairment.1
The manufacturer makes no specific dosage recommendations for geriatric patients.1
Cytokine Release Syndrome (CRS)
A boxed warning about the risk of CRS is included in the prescribing information for mosunetuzumab.1 Serious or life-threatening cases of CRS have been reported.1 In clinical trials, CRS occurred in 39% of patients who received the recommended dosage of mosunetuzumab.1 Grade 1 CRS occurred in 28% of patients, grade 2 in 15%, grade 3 in 2%, and grade 4 in 0.5%.1 Recurrent CRS occurred in 11% of patients.1 Most patients experienced CRS on day 1, 8, or 15 of the first cycle of treatment.1 CRS was also observed on day 1 of cycle 2 in 5% of patients and during subsequent cycles in 1% of patients.1
The time to CRS onset from the start of mosunetuzumab administration ranged from 0.1 hours to 16 days (median time to onset, 5 hours on day 1 of cycle 1; 28 hours on day 8 of cycle 1; 25 hours on day 15 of cycle 1; and 46 hours on day 1 of cycle 2).1 The median duration of CRS was 3 days (range, 1-29 days).1
Clinical signs and symptoms of CRS included, but were not limited to, fever, chills, hypotension, tachycardia, hypoxia, and headache.1 Concurrent neurologic adverse reactions occurred in 6% of patients and included but were not limited to headache, confusional state, and anxiety.1
Initiate treatment using the recommended step-up dosing schedule to reduce the risk of CRS.1 Administer pretreatment medications to reduce the risk of CRS, ensure adequate hydration, and monitor patients closely following administration.1 At the first sign of CRS, immediately evaluate patients for hospitalization, manage per current guidelines, and administer supportive care.1 Withhold mosunetuzumab until CRS resolves or permanently discontinue depending on severity.1 Advise patients who experience CRS or other adverse events that impair consciousness to avoid driving or operating heavy or potentially dangerous machinery until resolution.1
Neurologic Toxicity, Including Immune Effector Cell-Associated Neurotoxicity Syndrome
Mosunetuzumab-axgb can cause serious and life-threatening neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS).1
Neurologic toxicity occurred in 39% of patients receiving mosunetuzumab-axgb at the recommended dosage in clinical trials, with grade 3 toxicity occurring in 3% of patients.1 The most frequent neurologic toxicities were headache (21%), peripheral neuropathy (13%), dizziness (11%), and mental status changes including confusional state, disturbance in attention, cognitive disorder, delirium, encephalopathy, and somnolence (6%).1 ICANS was reported in 1% of patients (grade 1, 0.5%; grade 2, 0.5%).1
Among patients in a broader clinical trial population, ICANS or suspected ICANS occurred in 20 (2.1%) of 949 patients who received mosunetuzumab-axgb, with the most frequently occurring manifestations including confusional state and lethargy.1 Grade 1-2 events were reported in 19 patients with a single patient experiencing a grade 3 event.1 The median time to onset of ICANS was 17 days (range: 1-48 days) with resolution of 87% of cases after a median duration of 3 days (range: 1-20 days).1
Coadministration with other products that cause dizziness or mental status changes may increase the risk of neurologic toxicity.1
Monitor patients for signs and symptoms of neurologic toxicity.1 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.1 Withhold mosunetuzumab-axgb or permanently discontinue based on severity and follow management recommendations.1
Evaluate patients who experience tremors, dizziness, insomnia, severe neurotoxicity, or any other adverse reactions that impair consciousness.1 Advise patients at increased risk to avoid driving and refrain from operating heavy or dangerous machinery until resolution.1
Serious or fatal infections have been reported with mosunetuzumab-axgb.1 Serious infections, including opportunistic infections, occurred in 17% of patients receiving mosunetuzumab-axgb at the recommended dosage in clinical trials.1 Grade 3 or 4 infections occurred in 14% of patients, and fatal infections occurred in 0.9%.1 The most common grade 3 or greater infections were pneumonia, sepsis, and upper respiratory tract infection.1
Monitor patients for signs and symptoms of infection prior to and during treatment.1 Do not administer mosunetuzumab-axgb in the presence of active infection.1 Use caution in patients with a history of recurring or chronic infections (e.g., chronic, active Epstein-Barr Virus), underlying conditions that may predispose to infections, or significant prior immunosuppressive treatment.1 Administer prophylactic antimicrobials according to guidelines.1
Withhold or consider permanent discontinuation of mosunetuzumab-axgb based on severity.1
Hemophagocytic Lymphohistiocytosis
Fatal or serious hemophagocytic lymphohistiocytosis (HLH) has been reported with mosunetuzumab-axgb.1 Common manifestations of HLH include fever, elevated ferritin, hemophagocytosis, cytopenias, coagulopathy, hepatitis, and splenomegaly.1
Among patients in a broader clinical trial population, HLH occurred in 7 (0.5%) of 1536 patients who received mosunetuzumab-axgb, with most cases identified within the initial 28 days following treatment initiation.1 Of the 7 cases, 6 resulted in fatality and 4 occurred in the context of concurrent Epstein-Barr virus and/or cytomegalovirus infection.1
Patients should be monitored for clinical signs and symptoms of HLH.1 A HLH diagnosis should be considered when the presentation of CRS is atypical or prolonged, or when there are features of macrophage activation.1 If HLH is suspected, mosunetuzumab-axgb therapy should be interrupted and the patient evaluated and treated promptly for HLH per practice guidelines.1
Serious or severe cytopenias, including neutropenia, anemia, and thrombocytopenia, have been reported with mosunetuzumab-axgb.1 In clinical trials, grade 3 or 4 decreased neutrophils occurred in 38% of patients receiving mosunetuzumab-axgb at the recommended dosa decreased hemoglobin occurred in 19% of patients, and decreased platelets in 12% of patients.1 Grade 4 decreased neutrophils occurred in 19% and decreased platelets in 5% of patients.1 Febrile neutropenia occurred in 2%.1
Monitor CBC during treatment.1 Based on the severity of cytopenias, temporarily withhold or permanently discontinue mosunetuzumab-axgb.1 Consider prophylactic granulocyte colony-stimulating factor administration as applicable.1
Serious or severe tumor flare has been reported with mosunetuzumab-axgb.1 Tumor flare occurred in 4% of patients receiving mosunetuzumab-axgb at the recommended dosage in clinical trials.1 Manifestations included new or worsening pleural effusions, localized pain and swelling at the sites of lymphoma lesions, and tumor inflammation.1
Monitor for signs and symptoms of compression or obstruction due to mass effect secondary to tumor flare, particularly in patients with bulky tumors or disease located in close proximity to airways or a vital organ.1 If compression or obstruction develops, institute standard treatment of these complications.1
Fetal/Neonatal Morbidity and Mortality
Based on its mechanism of action, mosunetuzumab-axgb may cause fetal harm when administered to a pregnant woman.1 There are no human or animal data to evaluate for a drug-associated risk; however, immune activation by mosunetuzumab-axgb may compromise pregnancy maintenance, and exposure to mosunetuzumab-axgb in utero may cause B-cell lymphocytopenia in infants.1
Advise pregnant women of the potential risk to the fetus.1 Verify pregnancy status in females of reproductive potential prior to initiating mosunetuzumab-axgb.1 Advise females of reproductive potential to use effective contraception during treatment with mosunetuzumab-axgb and for 3 months after the last dose.1
When 418 patients were treated with mosunetuzumab-axgb for up to 12 months in a clinical trial, no patients developed anti-mosunetuzumab-axgb antibodies.1
There are no available data on the use of mosunetuzumab-axgb in pregnant women to evaluate for a drug-associated risk.1 No animal reproductive or developmental toxicity studies have been conducted with mosunetuzumab-axgb.1
Based on the mechanism of action, mosunetuzumab-axgb may cause fetal harm when administered to a pregnant woman.1 Mosunetuzumab-axgb causes T-cell activation and cytokine release; immune activation may compromise pregnancy maintenance.1 In addition, based on expression of CD20 on B cells and the finding of B cell depletion in non-pregnant animals, mosunetuzumab-axgb can cause B-cell lymphocytopenia in infants exposed to mosunetuzumab-axgb in utero.1 Human immunoglobulin G (IgG) is known to cross the placenta; therefore, mosunetuzumab-axgb has the potential to be transmitted from the mother to the developing fetus.1 Advise women of the potential risk to the fetus.1 Verify pregnancy status in females of reproductive potential prior to initiating mosunetuzumab-axgb.1
There are no data regarding the presence of mosunetuzumab-axgb in human milk, effects on the breast-fed infant, or effects on milk production.1 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 breast-feed during treatment with mosunetuzumab-axgb and for 3 months after the last dose.1
Females and Males of Reproductive Potential
Verify pregnancy status in females of reproductive potential prior to initiating mosunetuzumab-axgb.1 Advise females of reproductive potential to use effective contraception during treatment with mosunetuzumab-axgb and for 3 months after the last dose.1
The safety and effectiveness of mosunetuzumab-axgb in pediatric patients have not been established.1
Of the 90 patients with relapsed or refractory follicular lymphoma treated with mosunetuzumab-axgb, 33% were ≥65 years of age and 8% were ≥75 years of age.1 There is an insufficient number of patients in these age groups to assess whether there are differences in safety or effectiveness compared to younger adult patients.1
There were no clinically significant differences in the pharmacokinetics of mosunetuzumab-axgb in mild hepatic impairment (total bilirubin less than or equal to upper limit of normal [ULN] with AST greater than ULN OR total bilirubin >1 to 1.5 times ULN with any AST level).1 The effects of moderate to severe hepatic impairment (total bilirubin >1.5 times ULN with any AST) on the pharmacokinetics of mosunetuzumab-axgb are unknown.1
There were no clinically significant differences in the pharmacokinetics of mosunetuzumab-axgb in mild or moderate renal impairment (estimated creatinine clearance [Clcr] 30-89 mL/min).1 The effects of severe renal impairment (Clcr 15-29 mL/min) on the pharmacokinetics of mosunetuzumab-axgb are unknown.1
The most common adverse reactions (occurring in ≥20% of patients) are CRS, fatigue, rash, pyrexia, and headache.1 The most common Grade 3 to 4 laboratory abnormalities (occurring in ≥10% of patients) are decreased lymphocyte count, decreased phosphate, increased glucose, decreased neutrophil count, increased uric acid, decreased white blood cell count, decreased hemoglobin, and decreased platelets.1
No clinical studies evaluating the drug interaction potential of mosunetuzumab-axgb have been conducted.1
Drugs Metabolized by Hepatic Microsomal Enzymes
Mosunetuzumab-axgb causes release of cytokines that may suppress activity of cytochrome P450 (CYP) enzymes, resulting in increased exposure of CYP substrates.1 Increased exposure of CYP substrates is more likely to occur after the first dose of mosunetuzumab-axgb on Cycle 1 Day 1, up to 14 days after the second 60 mg dose on Cycle 2 Day 1, and during and after cytokine release syndrome (CRS).1 Monitor for toxicity or concentrations of drugs that are CYP substrates where minimal concentration changes may lead to serious adverse reactions.1 Consult the concomitant CYP substrate drug's prescribing information for recommended dosage modification.1
Mosunetuzumab-axgb is a T-cell engaging bispecific antibody that binds to the CD3 receptor (expressed on the surface of T cells) and CD20 (expressed on the surface of lymphoma cells and some healthy B-lineage cells).1 Mosunetuzumab-axgb activates T cells, causes release of proinflammatory cytokines, and induces lysis of B cells.1
After administration of the recommended dosage of mosunetuzumab-axgb, peripheral B cell counts decreased to undetectable levels in 92% of patients by Cycle 2 Day 1; sustained depletion was observed at Cycle 4 and Cycle 8.1 Among 67 patients with baseline immunoglobulin G (IgG) levels ≥500 mg/dL, 40% had a decrease in IgG level to <500 mg/dL after administration of mosunetuzumab-axgb.1 Transient elevations in plasma cytokine concentrations are observed after mosunetuzumab-axgb administration, with the highest elevations occurring within 24 hours after the first dose on Cycle 1 Day 1 and after the first 60 mg dose on Cycle 1 Day 15.1 Levels generally returned to baseline prior to the next infusion on Cycle 1 Day 8 and Cycle 2 Day 1.1
Mosunetuzumab-axgb exhibits dose-proportional pharmacokinetics over a dose range of 0.2-60 mg.1 Steady state is reached by Cycle 4 (63-84 days).1 The mean elimination half-life of mosunetuzumab-axgb is 16.1 days.1 Age (19-96 years), sex, race, and ethnicity had no clinically significant effects on the pharmacokinetics of mosunetuzumab-axgb.1
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Concentrate, for injection, for IV infusion | 1 mg/mL (1 mg and 30 mg) | Lunsumio® (available in single-dose vials) | Genentech |
AHFS® Drug Information. © Copyright, 1959-2026, Selected Revisions April 10, 2025. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
Only references cited for selected revisions after 1984 are available electronically.
1. Genentech, Inc. Lunsumio® (mosunetuzumab) INTRAVENOUS prescribing information. 2024 Nov.
2. Budde LE, Sehn LH, Matasar M, et al. Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study. Lancet Oncol . 2022;23(8):1055-1065.
3. US Food and Drug Administration. Search orphan drug designations and approvals. From FDA website. Accessed 2025 Feb 26. [Web]
4. PDQ® Adult Treatment Editorial Board. PDQ Non-Hodgkin Lymphoma Treatment. Bethesda, MD: National Cancer Institute. Updated 2024 Aug 22. Accessed 2025 Feb 26. [Web]
5. PDQ® Adult Treatment Editorial Board. PDQ B-Cell Non-Hodgkin Lymphoma Treatment. Bethesda, MD: National Cancer Institute. [Web]