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).

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NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend loncastuximab tesirine-lpyl (ZYNLONTA®) as a third-line and subsequent therapy option for patients with relapsed or refractory DLBCL who have received 2 systemic therapies (Category 2A).1,a

NCCN Guidelines also recommend loncastuximab tesirine-lpyl (ZYNLONTA®) after 2 lines of systemic therapies for patients with histologic transformation of follicular lymphoma or nodal marginal zone lymphoma to DLBCL (Category 2A).1,a

a It is unclear if tafasitamab or loncastuximab tesirine-lpyl or if any other CD19-directed therapy would have a negative impact on the efficacy of subsequent anti-CD19 CAR T-cell therapy.1

Intended for US healthcare professionals only.

Safety

ZYNLONTA® safety profile2

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

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

LOTIS-2 study (N=145)

Serious adverse reactions occurred in 28% of patients. The most common serious adverse reactions that occurred in ≥2% of patients were febrile neutropenia, pneumonia, edema, pleural effusion, and sepsis. Fatal adverse reactions occurred in 1% of patients, due to infection.

Permanent discontinuation due to an adverse reaction occurred in 19% of patients

Adverse reactions resulting in permanent discontinuation in ≥2% were GGT increased, edema, and effusion.

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

Adverse reaction resulting in dose reduction of ZYNLONTA® in ≥4% was GGT increased.

Dosage interruptions due to an adverse reaction occurred in 49% of patients

Adverse reactions leading to dose interruption in ≥5% were GGT 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.

GGT = gamma-glutamyltransferase.

Adverse reactions (≥10%) in 145 patients who received ZYNLONTA® in LOTIS-22

Adverse Reaction All Grades
(%)
Grade 3 or 4
(%)
General Disorders and Administration Site Conditions
Fatiguea 38 1b
Edemac 28 3b
Skin and Subcutaneous Tissue Disorders
Rashd 30 2b
Pruritus 12 0
Photosensitivity reaction 10 2b
Gastrointestinal Disorders
Nausea 23 0
Diarrhea 17 2b
Abdominal paine 14 3
Vomiting 13 0
Constipation 12 0
Musculoskeletal and Connective Tissue Disorders
Musculoskeletal painf 23 1b
Metabolism and Nutrition Disorders
Decreased appetite 15 0
Respiratory Disorders
Dyspneag 13 1b
Pleural effusion 10 2b
Infection
Upper respiratory tract infectionh 10 <1b

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.

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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 glutamyl transferase, 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.

DOSE DELAYS AND MODIFICATIONS

For any Grade 3 or greater nonhematologic toxicity, ZYNLONTA® should be held until the toxicity resolves to Grade 1 or less. For neutropenia: if absolute neutrophil count is <1 x 109/L, withhold ZYNLONTA® until the neutrophil count returns to 1 x 109/L or higher. For thrombocytopenia: if platelet count is <50,000/mcL, withhold ZYNLONTA® until the platelet count returns to 50,000/mcL or higher. For Grade 2 or greater edema or effusion, ZYNLONTA® should be held until the toxicity resolves to Grade 1 or less. If dosing is delayed by more than 3 weeks due to toxicity related to ZYNLONTA®, reduce subsequent doses by 50%. If toxicity reoccurs following dose reduction, consider discontinuation. Note: If toxicity requires dose reduction following the second dose of 0.15 mg/kg (C2D1), the patient should receive the dose of 0.075 mg/kg for Cycle 3.

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.

References: 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for B-Cell Lymphomas V.4.2021. © National Comprehensive Cancer Network, Inc. 2021. All rights reserved. Accessed May 5, 2021. To view the most recent and complete version of the guidelines, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 2. 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 glutamyl transferase, 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.

DOSE DELAYS AND MODIFICATIONS

For any Grade 3 or greater nonhematologic toxicity, ZYNLONTA® should be held until the toxicity resolves to Grade 1 or less. For neutropenia: if absolute neutrophil count is <1 x 109/L, withhold ZYNLONTA® until the neutrophil count returns to 1 x 109/L or higher. For thrombocytopenia: if platelet count is <50,000/mcL, withhold ZYNLONTA® until the platelet count returns to 50,000/mcL or higher. For Grade 2 or greater edema or effusion, ZYNLONTA® should be held until the toxicity resolves to Grade 1 or less. If dosing is delayed by more than 3 weeks due to toxicity related to ZYNLONTA®, reduce subsequent doses by 50%. If toxicity reoccurs following dose reduction, consider discontinuation. Note: If toxicity requires dose reduction following the second dose of 0.15 mg/kg (C2D1), the patient should receive the dose of 0.075 mg/kg for Cycle 3.

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.

References: 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for B-Cell Lymphomas V.4.2021. © National Comprehensive Cancer Network, Inc. 2021. All rights reserved. Accessed May 5, 2021. To view the most recent and complete version of the guidelines, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 2. Zynlonta® Prescribing information. ADC Therapeutics SA; 2021.

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