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For US healthcare
providers only

Full Prescribing
Information
Patient Site

Pooled safety analysis: Phase 1 and LOTIS-2 patients who
received ZYNLONTA™ at an initial dose of 0.15 mg/kg (N=215)1

The most common (>20%) adverse reactions, including laboratory abnormalities, were thrombocytopenia, increased gamma-
glutamyltransferase, neutropenia, anemia, hyperglycemia, transaminase elevation, fatigue, hypoalbuminemia, rash, edema,
nausea, and musculoskeletal pain.

Safety profile from LOTIS-2 study (N=145)1

Serious adverse reactions occurred in 28% of patients

The most common serious adverse reactions that occurred in ≥2% of patients receiving ZYNLONTA™ were febrile
neutropenia, pneumonia, edema, pleural effusion, and sepsis. Fatal adverse reactions occurred in 1% of patients, due to
infection.

Permanent discontinuation due to serious adverse reactions occurred in 19% of patients

Adverse reactions resulting in permanent discontinuation of ZYNLONTA™ in ≥2% of patients were gamma-
glutamyltransferase increased, edema, and effusion.

Dose reductions due to an adverse reaction with ZYNLONTA™ occurred in 8% of patients

Adverse reaction resulting in dose reduction of ZYNLONTA™ in ≥4% of patients 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% of patients were gamma-glutamyltransferase increased,
neutropenia, thrombocytopenia, and edema.

Specific populations

In LOTIS-2, 55% of patients were ≥65 years of age. No overall differences in safety or effectiveness were observed between
older (≥65 years) and younger patients.

Adverse reactions (≥10%) in 145 patients who received ZYNLONTA™ in the LOTIS-2 trial1

Table: Adverse reactions (≥10%) in 145 patients who received ZYNLONTA™ in the LOTIS-2 trial¹

aFatigue includes fatigue, asthenia, and lethargy.
bNo Grade 4 adverse reactions occurred.
cEdema includes edema, face edema, generalized edema, peripheral edema, ascites, fluid overload, peripheral swelling, swelling, and swelling face.
dRash includes rash, rash erythematous, rash maculopapular, rash pruritic, rash pustular, erythema, generalized erythema, dermatitis, dermatitis acneiform, dermatitis
 bullous, dermatitis exfoliative generalized, and palmar-plantar erythrodysesthesia syndrome.
eAbdominal pain includes abdominal pain, abdominal discomfort, abdominal pain lower, and abdominal pain upper.
fMusculoskeletal pain includes musculoskeletal pain, musculoskeletal chest pain, musculoskeletal discomfort, back pain, limb discomfort, myalgia, neck pain, non-
 cardiac chest pain, and pain in extremity.
gDyspnea includes dyspnea, and dyspnea exertional.
hUpper respiratory tract infection includes upper respiratory tract infection, upper respiratory tract congestion, nasopharyngitis, rhinitis, rhinovirus infection, and sinusitis.

Clinically relevant adverse reactions in <10% of patients (all grades) who received ZYNLONTA™ included:

  • Blood and lymphatic system disorders: Febrile neutropenia (3%)
  • Cardiac disorders: Pericardial effusion (3%)
  • Infections: Pneumoniaa (5%), sepsisb (2%)
  • Skin and subcutaneous disorders: Hyperpigmentation (4%)
  • General disorders: Infusion site extravasation (<1%)

aPneumonia includes pneumonia and lung infection.
bSepsis includes sepsis, escherichia sepsis, and septic shock.

Select laboratory abnormalities (≥10%) that worsened from baseline in patients who received ZYNLONTA™ in LOTIS-21

Table: Select laboratory abnormalities (≥10%) that worsened from baseline in patients who received ZYNLONTA™ in LOTIS-2¹ Table: Select laboratory abnormalities (≥10%) that worsened from baseline in patients who received ZYNLONTA™ in LOTIS-2¹

aThe denominator used to calculate the rate varied from 143 to 145 based on the number of patients with a baseline value and at least one post-treatment value.
bNo Grade 4 adverse reactions occurred.

ASL = alanine aminotransferase; AST = aspartate aminotransferase; DLBCL = diffuse large B-cell lymphoma; GGT = gamma-glutamyltransferase.

Indication and Usage

ZYNLONTA™ is 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 or 4 neutropenia occurred in 32%, thrombocytopenia in 20%, 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, rash (including exfoliative and maculo-papular), and erythema.

Monitor patients for new or worsening cutaneous reactions, including photosensitivity reactions. Withhold ZYNLONTA™ for severe (Grade 3) cutaneous reactions until resolution. 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) and 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 6 months after the last dose.

ADVERSE REACTIONS

In a pooled safety population of 215 patients (Phase 1 and LOTIS-2), the most common (>20%) adverse reactions, including laboratory abnormalities, were thrombocytopenia, increased gamma-glutamyltransferase, neutropenia, anemia, hyperglycemia, transaminase elevation, fatigue, hypoalbuminemia, rash, edema, nausea, and musculoskeletal pain.

In LOTIS-2, 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 see the full Prescribing Information for additional Important Safety Information.

Reference: 1. Zynlonta. Prescribing information. ADC Therapeutics SA; 2021.

Expand

Indication and Usage

ZYNLONTA™ is 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 or 4 neutropenia occurred in 32%, thrombocytopenia in 20%, 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, rash (including exfoliative and maculo-papular), and erythema.

Monitor patients for new or worsening cutaneous reactions, including photosensitivity reactions. Withhold ZYNLONTA™ for severe (Grade 3) cutaneous reactions until resolution. 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) and 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 6 months after the last dose.

ADVERSE REACTIONS

In a pooled safety population of 215 patients (Phase 1 and LOTIS-2), the most common (>20%) adverse reactions, including laboratory abnormalities, were thrombocytopenia, increased gamma-glutamyltransferase, neutropenia, anemia, hyperglycemia, transaminase elevation, fatigue, hypoalbuminemia, rash, edema, nausea, and musculoskeletal pain.

In LOTIS-2, 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 see the full Prescribing Information for additional Important Safety Information.

Reference: 1. Zynlonta. Prescribing information. ADC Therapeutics SA; 2021.