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INDICATION AND USAGE
ZYNLONTA is a CD19-targeted antibody and alkylating agent conjugate indicated for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from low grade lymphoma, and high grade B-cell lymphoma.
This indication is approved under accelerated approval based on overall 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
Effusion and Edema
Serious effusion and edema occurred in patients treated with ZYNLONTA. Grade 3 edema occurred in 3% (primarily peripheral edema or ascites) and Grade 3 pleural effusion occurred in 3% and Grade 3 or 4 pericardial effusion occurred in 1%.
Monitor patients for new or worsening edema or effusions. Withhold ZYNLONTA for Grade 2 or greater edema or effusion until the toxicity resolves. Consider diagnostic imaging in patients who develop symptoms of pleural effusion or pericardial effusion, such as new or worsened dyspnea, chest pain, and/or ascites such as swelling in the abdomen and bloating. Institute appropriate medical management for edema or effusions.
Myelosuppression
Treatment with ZYNLONTA can cause serious or severe myelosuppression, including neutropenia, thrombocytopenia, and anemia. Grade 3 neutropenia occurred in 11%, thrombocytopenia in 13%, and anemia in 12% of patients. Grade 4 neutropenia occurred in 21% and thrombocytopenia in 7% of patients. Febrile neutropenia occurred in 3%.
Monitor complete blood counts throughout treatment. Cytopenias may require interruption, dose reduction, or discontinuation of ZYNLONTA. Consider prophylactic granulocyte colony-stimulating factor administration as applicable.
Infections
Fatal and serious infections, including opportunistic infections, occurred in patients treated with ZYNLONTA. Grade 3 or higher infections occurred in 10% of patients, with fatal infections occurring in 2%. The most frequent Grade ≥3 infections included sepsis and pneumonia.
Monitor for any new or worsening signs or symptoms consistent with infection. For Grade 3 or 4 infection, withhold ZYNLONTA until infection has resolved.
Cutaneous Reactions
Serious cutaneous reactions occurred in patients treated with ZYNLONTA. Grade 3 cutaneous reactions occurred in 4% and included photosensitivity reaction, exfoliative rash, rash (primarily maculo-papular), and erythema. Additionally, 4% of patients experienced skin hyperpigmentation.
Monitor patients for new or worsening cutaneous reactions, including photosensitivity reactions. Withhold ZYNLONTA for severe (Grade 3) cutaneous reactions until resolution [see Dosage and Administration (2.3)]. Advise patients to minimize or avoid exposure to direct natural or artificial sunlight including exposure through glass windows. Instruct patients to protect skin from exposure to sunlight by wearing sun-protective clothing and/or the use of sunscreen products. If a skin reaction or rash develops, dermatologic consultation should be considered.
Embryo-Fetal Toxicity
Based on its mechanism of action, ZYNLONTA can cause embryo-fetal harm when administered to a pregnant woman because it contains a genotoxic compound (SG3199) which affects actively dividing cells.
Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with ZYNLONTA and for 9 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ZYNLONTA, and for 7 months after the last dose.
ADVERSE REACTIONS
In this pooled safety population of 215 patients, the most common (>20%) adverse reactions, including laboratory abnormalities, were thrombocytopenia, increased gamma glutamyl transferase, neutropenia, anemia, hyperglycemia, transaminase elevation, fatigue, hypoalbuminemia, rash, edema, nausea, and musculoskeletal pain.
In the Phase 2 trial serious adverse reactions occurred in 28% of patients receiving ZYNLONTA. The most common serious adverse reactions that occurred in ≥2% receiving ZYNLONTA were febrile neutropenia, pneumonia, edema, pleural effusion, and sepsis. Fatal adverse reactions occurred in 1%, due to infection.
Permanent treatment discontinuation due to an adverse reaction of ZYNLONTA occurred in 19% of patients. Adverse reactions resulting in permanent discontinuation of ZYNLONTA in ≥2% were gamma-glutamyltransferase increased, edema, and effusion.
Dose reductions due to an adverse reaction of ZYNLONTA occurred in 8% of patients. Adverse reactions resulting in dose reduction of ZYNLONTA in ≥4% was gamma-glutamyltransferase increased.
Dosage interruptions due to an adverse reaction occurred in 49% of patients receiving ZYNLONTA. Adverse reactions leading to interruption of ZYNLONTA in ≥5% were gamma-glutamyltransferase increased, neutropenia, thrombocytopenia, and edema.
You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to ADC Therapeutics at 1-855-690-0340.
Please click here for the full Prescribing Information, including Patient Information.
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