- Oncology drug research (https://voice.ons.org/topic/oncology-drug-research)
- U.S. Food and Drug Administration (FDA) (https://voice.ons.org/topic/us-food-and-drug-administration-fda)
- Clinical practice (https://voice.ons.org/topic/clinical-practice)
- Drug Reference Sheet (https://voice.ons.org/topic/drug-reference-sheet)
Oncology Drug Reference Sheet: Mosunetuzumab-Axgb
In an open-label, multicenter, multicohort study that included 90 patients with relapsed or refractory follicular lymphoma who had received at least two prior lines of systemic therapy, 60% of patients receiving treatment with mosunetuzumab-axgb achieved a complete response and 80% had an overall response (https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761263s000lbl.pdf). On December 22, 2022, the U.S. Food and Drug Administration (FDA) granted mosunetuzumab-axgb accelerated approval (https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-mosunetuzumab-axgb-relapsed-or-refractory-follicular-lymphoma) based on those findings.
Anti-CD20 x anti-CD3 bispecific monoclonal antibody
Mechanism of Action
The T cell–engaging bispecific antibody binds to (https://www.cancer.gov/publications/dictionaries/cancer-drug/def/anti-cd3-x-anti-cd20-bispecific-antibody-armed-activated-t-cells) the CD3 receptor on the surface of T cells and to CD20 on the surface of lymphoma cells and some healthy B-lineage cells. The action redirects T cells, releases proinflammatory cytokines, and engages and eliminates malignant B cells.
Adult patients with relapsed or refractory follicular lymphoma (https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761263s000lbl.pdf) who have received two or more lines of systemic therapy
|Treatment Day||Dosage||Infusion Rate|
|Cycle 1||Day 1||1 mg||Administer over a minimum of four hours.|
|Day 8||2 mg|
|Day 15||60 mg|
|Cycle 2||Day 1||60 mg||Administer over two hours if cycle 1 infusions were well tolerated.|
|Cycle 3||Day 1||30 mg|
Administer eight cycles every 21 days (https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761263s000lbl.pdf) unless patients experience unacceptable toxicity or disease progression. Those who achieve a complete response after eight cycles can stop treatment. Patients who achieve partial response or maintain stable disease after eight cycles can receive an additional nine cycles (17 cycles total) unless they experience unacceptable toxicity or disease progression.
Dosing and schedule recommendations for treatment reintroduction after delays for adverse reactions vary depending on the patient’s stage of step-up therapy before treatment suspension. See table 2 in section 2.2 of the package insert (https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761263s000lbl.pdf) for details.
Only qualified clinicians at locations with access to required medical support to manage severe reactions such as cytokine release syndrome (CRS) and neurologic toxicity may administer mosunetuzumab-axgb (https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761263s000lbl.pdf). Administer only as an IV infusion through a dedicated line. Do not use an inline filter, but you may use drip chamber filters.
Ensure patients are well hydrated; consult with the ordering provider to determine the need for IV hydration. Premedicate all patients with a corticosteroid, antihistamine, and antipyretic agent prior to cycles 1 and 2 to reduce the risk of CRS and infusion-related reactions. Continue premedications for all future cycles in the event CRS occurs. See section 2.3 of the package insert (https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761263s000lbl.pdf) for recommended agents and doses.
Mosunetuzumab-axgb has a boxed warning for CRS (https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761263s000lbl.pdf), which can be serious or life threatening. Clinical manifestations include fever, chills, hypotension, tachycardia, hypoxia, and headache.
Additional warnings and precautions (https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761263s000lbl.pdf) include neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS) (e.g., headache, peripheral neuropathy, dizziness, mental status changes); serious or fatal infections (e.g., pneumonia, sepsis, upper respiratory tract infection, opportunistic infections); cytopenias (e.g., neutropenia, anemia, thrombocytopenia); tumor flare (e.g., new or worsening pleural effusions, localized pain, swelling at sites of lymphoma burden); and embryo-fetal toxicity if administered to pregnant patients.
At least 20% of the study participants also experienced (https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761263s000lbl.pdf) fatigue, rash, pyrexia, and headache. The most common laboratory abnormalities included decreased phosphate, increased glucose, and increased uric acid.
To reduce the risk of severe CRS, follow all recommendations (https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761263s000lbl.pdf) for hydration, premedication, and step-up dosing. At the first sign of CRS or neurologic toxicity (including ICANS), immediately stop the infusion, evaluate the patient, and initiate supportive care and management following your current practice guidelines. Prepare for possible hospitalization and interdisciplinary consultations (e.g., hospitalist, neurology).
Monitor patients for signs and symptoms of infection (https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761263s000lbl.pdf) prior to and during treatment and notify the provider about any concerning observations. Do not administer mosunetuzumab-axgb to patients with an active infection. Patients with history of chronic infection or prior immunosuppressive treatment may require prophylactic antimicrobials. Monitor patients’ complete blood count throughout treatment, as ordered by the provider, and consider prophylactic granulocyte colony-stimulating factor administration if warranted.
Monitor patients with bulky tumor burden near their airways or vital organs for signs or symptoms of obstruction or compression because of mass effect or tumor flare.
Watch for signs and symptoms of CRS and neurologic toxicity (https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761263s000lbl.pdf), including ICANS, and seek immediate medical attention if symptoms appear at any time. If you experience CRS or neurologic toxicity, do not drive or operate heavy or potentially dangerous machinery until your symptoms fully resolve.
Immediately report any signs or symptoms of cytopenias and infections (https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761263s000lbl.pdf) to your care team. You may also be at risk for tumor flare; notify your care team about any new or worsening symptoms.
Avoid pregnancy and breastfeeding and use effective contraception (https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761263s000lbl.pdf) during treatment and for three months after the last dose. If you do become pregnant during treatment, notify your care team immediately.
Current data is insufficient (https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761263s000lbl.pdf) to evaluate differences or precautions for patients aged 65 and older compared to younger adults. Safety and efficacy have not been established in pediatric patients. No carcinogenicity or genotoxicity studies have been conducted.
The National Institute for Occupational Safety and Health does not classify unconjugated monoclonal antibodies as hazardous (https://www.cdc.gov/niosh/docs/2016-161/default.html). Review your institution’s hazardous drug classification and safe handling procedures to ensure you understand and comply with your local policy.
The manufacturer offers financial assistance options online (https://www.lunsumio-hcp.com/financial-support/assistance-options.html) or by phone at 888-249-4918 from 6 am–5 pm PST, Monday–Friday.