Kymriah Side Effects Center

Last updated on RxList: 9/13/2017
Kymriah Side Effects Center

Last reviewed on RxList 9/13/2017

Kymriah (tisagenlecleucel) is aCD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse. Common side effects of Kymriah include:

Dosing of Kymriah is based on the number of chimeric antigen receptor (CAR) positive viable T cells. For patients 50 kg or less, administer 0.2 to 5.0x 106 CAR-positive viable T cells per kg bodyweight intravenously. For patients above 50 kg, administer 0.1 to 2.5 x 108 total CAR-positive viable T cells (non-weight based) intravenously. Kymriah may interact with some commercial HIV nucleic acid test (NAT) tests, causing them to yield false-positive results. Tell your doctor all medications and supplements you use. Kymriah is not recommended for use during pregnancy; it may harm a fetus. It is unknown if Kymriah passes into breast milk. Consult your doctor before breastfeeding.

Our Kymriah (tisagenlecleucel) 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.

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Kymriah 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.

A serious side effect of tisagenlecleucel is called cytokine release syndrome (CRS). Tell your caregivers right away if you have signs of this condition: fever, chills, trouble breathing, body aches, vomiting, diarrhea, or feeling light-headed. Your caregivers will have medication available to quickly treat CRS if it occurs.

Also tell your caregivers or seek emergency medical attention if you have signs of life-threatening nerve problems: problems with speech, problems with thinking or memory, confusion, or a seizure.

Also call your doctor at once if you have:

  • headaches, unusual tiredness;
  • tremors, anxiety, agitation;
  • unusual thoughts or behavior;
  • trouble speaking or understanding what is said to you; or
  • signs of infection--fever, chills, flu symptoms, mouth sores, skin sores, easy bruising or bleeding, cough, trouble breathing.

Common side effects may include:

  • nausea, vomiting, diarrhea, loss of appetite;
  • fever;
  • headache, confusion, feeling tired;
  • bleeding; or
  • fast heartbeats.

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.

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Kymriah Professional Information

SIDE EFFECTS

Most common adverse reactions (incidence greater than 20%) are hypogammaglobulinemia, infections-pathogen unspecified, pyrexia, decreased appetite, headache, encephalopathy, bleeding, hypotension, tachycardia, nausea, diarrhea, vomiting, viral infectious disorders, hypoxia, fatigue, acute kidney injury, and delirium.

The following serious adverse reactions are discussed in greater detail in another section of the label:

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 KYMRIAH in the clinical trial (Study 1) in which 68 patients with pediatric and young adult relapsed/ refractory (R/R) B-cell ALL received CAR-positive viable T cells.

Based on a recommended dose which was weight-based, all patients received a single intravenous dose of KYMRIAH [see Clinical Studies]. The most common adverse reactions were cytokine release syndrome (79%), hypogammaglobulinemia (43%), infections-pathogen unspecified (41%), pyrexia (40%), decreased appetite (37%), headache (37%), encephalopathy (34%), hypotension (31%), bleeding episodes (31%), tachycardia (26%), nausea (26%), diarrhea (26%), vomiting (26%), viral infectious disorders (26%), hypoxia (24%), fatigue (22%), acute kidney injury (22%), and delirium (21%).

Eleven deaths were reported for patients who received KYMRIAH, of which 2 deaths occurred within 30 days of infusion. Seven were disease-related, three were attributed to infections, and one to intracerebral hemorrhage. Of the two deaths before Day 30, one patient died with CRS and progressive leukemia and the second patient had resolving CRS with abdominal compartment syndrome, coagulopathy, and renal failure when an intracranial hemorrhage occurred.

The adverse reactions with greater or equal to 10% incidence for any Grade are summarized in Table 2.

Table 2: Selected Adverse Reactions (≥ 10%) Following Treatment with KYMRIAH (N=68)

Adverse Reaction All Grades (%) Grades 3 or Higher (%)
Cardiac disorders
aTachycardia 26 4
Gastrointestinal disorders
Nausea 26 3
Diarrhea 26 1
Vomiting 26 1
Constipation 18 0
bAbdominal pain 16 3
General disorders and administration site conditions
Pyrexia 40 15
Fatigue 22 0
Face edema 10 1
Edema peripheral 10 1
Chills 10 0
Immune system disorders
Cytokine release syndrome 79 49
cHypogammaglobulinemia 43 7
Infections and infestations
Infections-pathogen unspecified 41 16
Viral infectious disorders 26 18
Bacterial infectious disorders 19 13
Fungal infectious disorders 13 7
Investigations
International normalized ratio increased 13 0
Metabolism and nutrition disorders
Decreased appetite 37 15
Fluid overload 10 7
Musculoskeletal and connective tissue disorders
Pain in extremity 16 1
Myalgia 15 0
Arthralgia 12 1
Back pain 10 3
Nervous system disorders
dHeadache 37 3
eEncephalopathy 34 10
Psychiatric disorders
fDelirium 21 4
Anxiety 13 3
Renal and urinary disorders
gAcute kidney injury 22 13
Respiratory, thoracic and mediastinal disorders
Hypoxia 24 18
Cough 19 0
Pulmonary edema 16 10
Tachypnea 12 6
Pleural effusion 10 4
Nasal congestion 10 0
Vascular disorders
Hypotension 31 22
Hypertension 19 6
aTachycardia includes tachycardia and sinus tachycardia.
bAbdominal pain includes abdominal pain, abdominal pain upper, gastrointestinal pain, abdominal pain lower.
cHypogammaglobulinemia includes hypogammaglobulinemia, immunoglobulins decreased, blood immunoglobulin G decreased, blood immunoglobulin A decreased, blood immunoglobulin M decreased, hypogammaglobulinemia.
dHeadache includes headache and migraine.
eEncephalopathy includes encephalopathy, cognitive disorder, confusional state, depressed level of consciousness, disturbance in attention, lethargy, mental status changes, posterior reversible encephalopathy syndrome, somnolence, and automatism.
fDelirium includes delirium, agitation, hallucination, hallucination visual, irritability, restlessness.
gAcute kidney injury includes acute kidney injury, anuria, azotemia, renal failure, renal tubular dysfunction, renal tubular necrosis.

Additional important adverse reactions that did not meet the threshold criteria for inclusion in Table 2 were:

Blood and lymphatic system disorders: disseminated intravascular coagulation (9%), histiocytosis lymphocytic hemophagocytosis (7%), coagulopathy (6%), Grade 3 and Grade 4 hypofibrinogenemia with Grade 3 and 4 CRS (16%)

Cardiac Disorders: cardiac arrest (4%), cardiac failure (7%)

Gastrointestinal disorders: abdominal compartment syndrome (1%)

General disorders and administration site conditions: multiple organ dysfunction syndrome (3%)

Immune system disorders: graft versus host disease (1%)

Investigations: blood creatinine increased (7%), activated partial thromboplastin time prolonged (6%)

Nervous System: intracranial hemorrhage (1%), seizure (3%)

Respiratory, thoracic, and mediastinal disorders: respiratory distress (6%), respiratory failure (6%), acute respiratory distress syndrome (4%)

Metabolism and nutrition disorders: tumor lysis syndrome (6%)

Vascular disorders: capillary leak syndrome (3%)

Laboratory Abnormalities

Selected laboratory abnormalities worsening from baseline Grade 0-2 to Grade 3-4 are shown in Table 3.

Table 3: Selected Other Laboratory Abnormalities Worsening from Baseline Grade 0-2 to Grade 3-4 Following Treatment with KYMRIAH based on CTCAEa (N=68)

  Grade 3 or 4 (%)
Increased Aspartate Aminotransferase 28
Hypokalemia 27
Increased Alanine Aminotransferase 21
Increased bilirubin 21
Hypophosphatemia 19
aCTCAE = Common Terminology Criteria for Adverse Events version 4.03

All patients experienced neutropenia, anemia and thrombocytopenia. See Table 4 for the incidences of Grade 3 and Grade 4 prolonged thrombocytopenia and prolonged neutropenia in responding patients.

Table 4: Prolonged Cytopenias Following Treatment with KYMRIAH

  N=52 (%)
Day 28 Day 56
Prolonged neutropeniaa 40 17
Prolonged thrombocytopeniaa 27 12
aGrade 3 and 4 observed within 14 days after Day 28 or Day 56 in responding patients

Immunogenicity

In clinical studies, humoral immunogenicity of KYMRIAH was measured by determination of anti-murine CAR19 antibodies (anti-m CAR19) in serum pre- and post-administration. The majority of patients (86%) tested positive for pre-dose anti-m CAR19 antibodies in Study 1; however, the preexisting and treatment-induced antibodies were not associated with an impact on clinical response and did not have an impact on the initial expansion and persistence of KYMRIAH. Persistence of KYMRIAH was similar between patients with positive post-infusion anti-m CAR19 antibodies compared with patients with negative post-infusion anti-m CAR19 antibodies. There is no evidence that the presence of preexisting and treatment-induced anti-mCAR19 antibodies impact the safety or effectiveness of KYMRIAH.

Read the entire FDA prescribing information for Kymriah (Tisagenlecleucel Suspension for Intravenous Infusion)

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

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