Medical Editor: John P. Cunha, DO, FACOEP
Yescarta (axicabtagene ciloleucel) is a CD19-directed genetically modified autologous T cell immunotherapy 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, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma. Common side effects of Yescarta include:
- cytokine release syndrome,
- low blood pressure (hypotension),
- brain disease (encephalopathy),
- fast heart rate, fatigue,
- decreased appetite,
- low white blood cell count with fever,
- low blood oxygen,
- and irregular heartbeats.
Administer a lymphodepleting regimen of cyclophosphamide and fludarabine before infusion of Yescarta. Premedicate with acetaminophen and an H1-antihistamine. The target Yescarta dose is 2 × 106 CAR-positive viable T cells per kg body weight, with a maximum of 2 × 108 CAR-positive viable T cells. Yescarta may interact with other drugs. Tell your doctor all medications and supplements you use. Yescarta is not recommended for use during pregnancy. It may harm a fetus. Pregnancy after Yescarta infusion should be discussed with the treating physician. It is unknown if Yescarta passes into breast milk. Consult your doctor before breastfeeding.
Our Yescarta (Axicabtagene Ciloleucel) Suspension for Intravenous Infusion 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.
The following adverse reactions are described elsewhere in the labeling:
- Cytokine Release Syndrome [see WARNINGS AND PRECAUTIONS]
- Neurologic Toxicities [see WARNINGS AND PRECAUTIONS]
- Hypersensitivity Reactions [see WARNINGS AND PRECAUTIONS]
- Serious Infections [see WARNINGS AND PRECAUTIONS]
- Prolonged Cytopenias [see WARNINGS AND PRECAUTIONS]
- Hypogammaglobulinemia [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 safety data described in this section reflect exposure to YESCARTA in the clinical trial (Study 1) in which 108 patients with relapsed/refractory B-cell NHL received CAR-positive T cells based on a recommended dose which was weight-based [see Clinical Trials]. Patients with a history of CNS disorders (such as seizures or cerebrovascular ischemia) or autoimmune disease requiring systemic immunosuppression were ineligible. The median duration of follow up was 8.7 months. The median age of the study population was 58 years (range: 23 to 76 years); 68% were men. The baseline ECOG performance status was 43% with ECOG 0, and 57% with ECOG 1.
The most common adverse reactions (incidence ≥ 20%) include CRS, fever, hypotension, encephalopathy, tachycardia, fatigue, headache, decreased appetite, chills, diarrhea, febrile neutropenia, infections-pathogen unspecified, nausea, hypoxia, tremor, cough, vomiting, dizziness, constipation, and cardiac arrhythmias. Serious adverse reactions occurred in 52% of patients. The most common serious adverse reactions (> 2%) include encephalopathy, fever, lung infection, febrile neutropenia, cardiac arrhythmia, cardiac failure, urinary tract infection, renal insufficiency, aphasia, cardiac arrest, Clostridium difficile infection, delirium, hypotension, and hypoxia.
The most common (≥ 10%) Grade 3 or higher reactions include febrile neutropenia, fever, CRS, encephalopathy, infections-pathogen unspecified, hypotension, hypoxia and lung infections.
Forty-five percent (49/108) of patients received tocilizumab after infusion of YESCARTA.
Table 3 summarizes the adverse reactions that occurred in at least 10% of patients treated with YESCARTA and Table 4 describes the laboratory abnormalities of Grade 3 or 4 that occurred in at least 10% of patients.
Table 3: Summary of Adverse Reactions Observed
in at Least 10% of the Patients Treated with YESCARTA in Study 1
|Adverse Reaction||Any Grade (%)||Grade 3 or Higher (%)|
|General Disorders And Administration Site Conditions|
|Immune System Disorders|
|Cytokine release syndrome||94||13|
|Infections And Infestations|
|Musculoskelatal And Connective Tissue Disorders|
|Pain in extremityh||17||2|
|Nervous System Disorders|
|Respiratory, Thoracic And Mediastinal Disorders|
|Renal and Urinary Disorders|
|The following events were also counted in the incidence
of CRS: tachycardia, arrhythmia, fever, chills, hypoxia, renal insufficiency,
aTachycardia includes tachycardia, sinus tachycardia.
bArrhythmia includes arrhythmia, atrial fibrillation, atrial flutter, atrioventricular block, bundle branch block right, electrocardiogram QT prolonged, extra-systoles, heart rate irregular, supraventricular extra systoles, supraventricular tachycardia, ventricular arrhythmia, ventricular tachycardia.
cAbdominal pain includes abdominal pain, abdominal pain lower, abdominal pain upper.
dFatigue includes fatigue, malaise.
eEdema includes face edema, generalized edema, local swelling, localized edema, edema, edema genital, edema peripheral, periorbital edema, peripheral swelling, scrotal edema.
fHypogammaglobulinemia includes hypogammaglobulinemia, blood immunoglobulin D decreased, blood immunoglobulin G decreased.
gMotor dysfunction includes muscle spasms, muscular weakness.
hPain in extremity includes pain not otherwise specified, pain in extremity.
iEncephalopathy includes cognitive disorder, confusional state, depressed level of consciousness, disturbance in attention, encephalopathy, hypersomnia, leukoencephalopathy, memory impairment, mental status changes, paranoia, somnolence, stupor.
jHeadache includes headache, head discomfort, sinus headache, procedural headache.
kDizziness includes dizziness, presyncope, syncope.
lAphasia includes aphasia, dysphasia.
mDelirium includes agitation, delirium, delusion, disorientation, hallucination, hyperactivity, irritability, restlessness.
nHypoxia includes hypoxia, oxygen saturation decreased.
oCough includes cough, productive cough, upper-airway cough syndrome.
pDyspnea includes acute respiratory failure, dyspnea, orthopnea, respiratory distress.
qHypotension includes diastolic hypotension, hypotension, orthostatic hypotension.
rThrombosis includes deep vein thrombosis, embolism, embolism venous, pulmonary embolism, splenic infarction, splenic vein thrombosis, subclavian vein thrombosis, thrombosis, thrombosis in device.
Other clinically important adverse reactions that occurred in less than 10% of patients treated with YESCARTA include the following:
- Blood and lymphatic system disorders: Coagulopathy (2%)
- Cardiac disorders: Cardiac failure (6%) and cardiac arrest (4%)
- Immune system disorders: Hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS) (1%), hypersensitivity (1%)
- Infections and infestations disorders: Fungal infections (5%)
- Nervous system disorders: Ataxia (6%), seizure (4%), dyscalculia (2%), and myoclonus (2%)
- Respiratory, thoracic and mediastinal disorders: Pulmonary edema (9%)
- Skin and subcutaneous tissue disorders: Rash (9%)
- Vascular disorders: Capillary leak syndrome (3%)
Table 4: Grade 3 or 4
Laboratory Abnormalities Occurring in ≥ 10% of Patients in Study 1
Following Treatment with YESCARTA based on CTCAE (N=108)
|Grades 3 or 4 (%)|
|Uric acid increased||13|
|Direct Bilirubin increased||13|
|Alanine Aminotransferase increased||10|
YESCARTA has the potential to induce anti-product antibodies. The immunogenicity of YESCARTA has been evaluated using an enzyme-linked immunosorbent assay (ELISA) for the detection of binding antibodies against FMC63, the originating antibody of the anti-CD19 CAR. Three patients tested positive for pre-dose anti-FMC63 antibodies at baseline and Months 1, 3, or 6 in Study 1. There is no evidence that the kinetics of initial expansion and persistence of YESCARTA, or the safety or effectiveness of YESCARTA, was altered in these patients.
Read the entire FDA prescribing information for Yescarta (Axicabtagene Ciloleucel Suspension for Intravenous Infusion)