Zynlonta

Last updated on RxList: 7/22/2021
Zynlonta Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

What is Zynlonta and how is it used?

Zynlonta (loncastuximab tesirine-lpyl) is a CD19-directed antibody and alkylating agent conjugate used to treat 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.

Zynlonta may cause serious side effects including:

Dosage for Zynlonta

The dose of Zynlonta is administered as an intravenous infusion over 30 minutes on day 1 of each cycle (every 3 weeks). The recommended dosage of Zynlonta is 0.15 mg/kg every 3 weeks for 2 cycles, and 0.075 mg/kg every 3 weeks for subsequent cycles.

Zynlonta In Children

Safety and effectiveness of Zynlonta in pediatric patients have not been established.

What Drugs, Substances, or Supplements Interact with Zynlonta?

Zynlonta may interact with other medicines.

Tell your doctor all medications and supplements you use.

Zynlonta During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant before using Zynlonta; it may harm a fetus. Pregnancy testing is recommended for females of reproductive potential prior to initiating Zynlonta. Women of reproductive potential are advised to use effective contraception during treatment with Zynlonta and for 9 months after the last dose. Males with female partners of reproductive potential are advised to use effective contraception during the treatment with Zynlonta and for 6 months after the last dose. It is unknown if Zynlonta passes into breast milk. Because of the potential for serious adverse reactions in breastfed children, breastfeeding is not recommended during treatment with Zynlonta and for 3 months after the last dose.

Additional Information

Our Zynlonta (loncastuximab tesirine-lpyl) for Injection, for Intravenous Use Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Zynlonta Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

  • new or worsening skin rash, peeling, redness, or irritation;
  • new or worsening swelling, weight gain, chest pain, shortness of breath, or trouble breathing;
  • fluid build-up in or around the lungs--pain when you breathe, feeling short of breath while lying down, wheezing, gasping for breath, cough with foamy mucus, cold and clammy skin, anxiety, rapid heartbeats;
  • low blood cell counts--fever, chills, tiredness, mouth sores, skin sores, easy bruising, unusual bleeding, pale skin, cold hands and feet, feeling light-headed or short of breath; or
  • signs of a serious infection--flu symptoms, cough, weakness, body aches, headache, trouble breathing, or skin wounds with pain, redness, warmth, or swelling.

Common side effects may include:

  • tiredness or weakness;
  • rash;
  • swelling;
  • nausea;
  • muscle or joint pain;
  • increase in blood sugar; or
  • changes in blood or lab tests.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Zynlonta (Loncastuximab Tesirine-lpyl for Injection)

Zynlonta Professional Information

SIDE EFFECTS

The following clinically significant adverse reactions are described elsewhere in the labeling:

Effusion and Edema [see WARNINGS AND PRECAUTIONS]

Myelosuppression [see WARNINGS AND PRECAUTIONS]

Infections [see WARNINGS AND PRECAUTIONS]

Cutaneous Reactions [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The pooled safety population described in the WARNINGS AND PRECAUTIONS reflect exposure to ZYNLONTA as a single agent at an initial dose of 0.15 mg/kg in 215 patients with DLBCL in studies ADCT-402-201 (LOTIS-2) and ADCT-402-101, which includes 145 patients from LOTIS-2 treated with 0.15 mg/kg x 2 cycles followed by 0.075 mg/kg for subsequent cycles. Among 215 patients who received ZYNLONTA, the median number of cycles was 3 (range 1 to 15) with 58% receiving three or more cycles and 30% receiving five or more cycles.

In this pooled safety population of 215 patients, the most common (>20%) adverse reactions, including laboratory abnormalities, were thrombocytopenia, increased gamma­glutamyltransferase, neutropenia, anemia, hyperglycemia, transaminase elevation, fatigue, hypoalbuminemia, rash, edema, nausea, and musculoskeletal pain.

Relapsed Or Refractory Diffuse Large B-Cell Lymphoma

LOTIS-2

The safety of ZYNLONTA was evaluated in LOTIS-2, an open-label, single-arm clinical trial that enrolled 145 patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), including high grade B-cell lymphoma, after at least two prior systemic therapies [see Clinical Studies]. The trial required hepatic transaminases, including gamma-glutamyltransferase (GGT), ≤2.5 times upper limit of normal (ULN), total bilirubin ≤1.5 times ULN, and creatinine clearance ≥60 mL/min. Patients received ZYNLONTA 0.15 mg/kg every 3 weeks for 2 cycles, then 0.075 mg/kg every 3 weeks for subsequent cycles and received treatment until progressive disease or unacceptable toxicity. Among the 145 patients, the median number of cycles received was 3, with 34% receiving 5 or more cycles.

The median age was 66 years (range 23 to 94), 59% were male, and 94% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Race was reported in 97% of patients; of these patients, 90% were White, 3% were Black, and 2% were Asian.

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 gamma­glutamyltransferase increased, neutropenia, thrombocytopenia, and edema.

Table 1 summarizes the adverse reactions in LOTIS-2.

Table 1: Adverse Reactions (≥10%) in Patients with Relapsed or Refractory DLBCL who received ZYNLONTA in LOTIS-2

Adverse Reaction ZYNLONTA
(N=145)
All Grades (%) Grades 3 or 4 (%)
General Disorders and Administration Site Conditions
Fatigueb 38 1a
Edemac 28 3a
Skin and Subcutaneous Tissue Disorders
Rashd 30 2a
Pruritus 12 0
Photosensitivity reaction 10 2a
Gastrointestinal Disorders
Nausea 23 0
Diarrhea 17 2a
Abdominal paine 14 3
Vomiting 13 0
Constipation 12 0
Musculoskeletal and Connective Tissue Disorders
Musculoskeletal painf 23 1a
Metabolism and Nutrition Disorders
Decreased appetite 15 0
Respiratory Disorders
Dyspneag 13 1a
Pleural effusion 10 2a
Infection
Upper respiratory tract infectionh 10 <1a
a No Grade 4 adverse reactions occurred
b Fatigue includes fatigue, asthenia, and lethargy
c Edema includes edema, face edema, generalized edema, peripheral edema, ascites, fluid overload, peripheral swelling, swelling, and swelling face
d Rash 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
e Abdominal pain includes abdominal pain, abdominal discomfort, abdominal pain lower, and abdominal pain upper
f Musculoskeletal pain includes musculoskeletal pain, musculoskeletal chest pain, musculoskeletal discomfort, back pain, limb discomfort, myalgia, neck pain, non-cardiac chest pain, and pain in extremity
g Dyspnea includes dyspnea, and dyspnea exertional
h Upper 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%)

a Pneumonia includes pneumonia and lunginfection
b Sepsis includes sepsis, escherichia sepsis, and septic shock

Selected Other Adverse Reactions

Inflammatory-related conditions were reported in 3% of patients in LOTIS-2, including pericarditis, pneumonitis, pleuritis, and dermatitis.

Table 2 summarizes the laboratory abnormalities in LOTIS-2.

Table 2: Select Laboratory Abnormalities (≥10%) That Worsened from Baseline in Patients with Relapsed or Refractory DLBCL Who Received ZYNLONTA in LOTIS-2

Laboratory Abnormality ZYNLONTAa
All Grades (%) Grade 3 or 4 (%)
Hematologic
Platelets decreased 58 17
Neutrophils decreased 52 30
Hemoglobin decreased 51 10b
Chemistry
GGT increased 57 21
Glucose increased 48 8
AST increased 41 <1b
Albumin decreased 37 <1b
ALT increased 34 3
a The 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
b No Grade 4 adverse reactions occurred

Immunogenicity

As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies in the studies described below with the incidence of antibodies to loncastuximab tesirine-lpyl in other studies or to other products may be misleading.

In LOTIS-2, 0 of 134 patients tested positive for antibodies against loncastuximab tesirine-lpyl after treatment. The potential effect of anti-drug antibodies to ZYNLONTA on pharmacokinetics, efficacy, or safety is unknown.

DRUG INTERACTIONS

No Information provided

Read the entire FDA prescribing information for Zynlonta (Loncastuximab Tesirine-lpyl for Injection)

© Zynlonta Patient Information is supplied by Cerner Multum, Inc. and Zynlonta Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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