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Safety

Management of Capillary Leak Syndrome (CLS)

Download the CLS Management Guide for important information about ELZONRIS and CLS.

Common signs and symptoms associated with CLS that were reported during treatment with ELZONRIS include1:

  • Hypoalbuminemia
  • Edema
  • Weight gain
  • Hypotension

CLS incidence in patients receiving ELZONRIS in clinical trials1

Overall incidence of CLS was 55% (52/94)

  • 7% incidence of grade 3 or 4 events (7/94)
  • 2% incidence of grade 5 events resulted in death (2/94)
    • Grade 3 = severe; grade 4 = life-threatening; grade 5 = fatal.

Assess and monitor patients appropriately1

  • Before initiating therapy with ELZONRIS, ensure that the patient has adequate cardiac function and serum albumin ≥ 3.2 g/dL
  • During treatment, assess patients for common signs/symptoms of CLS before each dose is given, such as
    • Weight gain ≥ 1.5 kg over pretreatment weight on prior treatment day
    • New onset or worsening edema, including pulmonary edema
    • Hypotension or hemodynamic instability
    • Hypoalbuminemia
      • Serum albumin < 3.5 g/dL or reduced by ≥ 0.5 g/dL compared to the value measured prior to dosing initiation of the current cycle
  • Follow the CLS management guidelines found in section 2.2 (Table 2) of the full Prescribing Information

Time of presentation

CLS SIGN/SYMPTOM

Recommended Action

ELZONRIS dosing management

Prior to first dose of ELZONRIS in cycle 1

Serum albumin < 3.2 g/dL

Administer ELZONRIS when serum albumin ≥ 3.2 g/dL

Interrupt ELZONRIS dosing until the relevant CLS sign/symptom has resolved.a

During
ELZONRIS
dosing

Serum albumin < 3.5 g/dL

Administer 25g intravenous albumin (q12h or more frequently as practical) until serum albumin is ≥ 3.5 g/dL AND not more than 0.5 g/dL lower than the value measured prior to dosing initiation of the current cycle

Serum albumin reduced by ≥ 0.5 g/dL from the albumin value measured prior to ELZONRIS dosing initiation of the current cycle

A predose body weight that is increased by ≥ 1.5 kg over the previous day's predose weight

Administer 25 g intravenous albumin (q12h or more frequently as practical) and manage fluid status as indicated clinically (eg. generally with intravenous fluids and vasopressors if hypotensive and with diuretics if normotensive or hypertensive) until body weight increase has resolved (ie. the increase is no longer ≥ 1.5 kg greater than the previous day's predose weight)

Edema, fluid overload, and/or hypotension

Administer 25 g intravenous albumin (q12h, or more frequently as practical) until serum albumin is ≥ 3.5 g/dL

Administer 1 mg/kg of methylprednisolone (or an equivalent) per day until resolution of CLS sign/symptom or as indicated clinically


Aggresive management of fluid status and hypotension if present, which could include intravenous fluids and/or diuretics or other blood pressure management, until resolution of CLS sign/symptom or as clinically indicated

aELZONRIS administration may resume in the same cycle if all CLS signs/symptoms have resolved and the patient did not require measures to treat hemodynamic instability. ELZONRIS administration should be held for the remainder of the cycle if CLS signs/symptoms have not resolved or the patient required measures to treat hemodynamic instability (eg, required administration of intravenous fluids and/or vasopressors to treat hypotension), even if resolved, and ELZONRIS administration may only resume in the next cycle if all CLS signs/symptoms have resolved, and the patient is hemodynamically stable.

See how to properly prepare ELZONRIS

Reference: 1. ELZONRIS [prescribing information]. New York, NY, US: Stemline Therapeutics, Inc.; December 2018.

INDICATION

  • ELZONRIS is a CD123-directed cytotoxin for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and in pediatric patients 2 years and older

IMPORTANT SAFETY INFORMATION

Boxed WARNING: CAPILLARY LEAK SYNDROME

  • Capillary Leak Syndrome (CLS), which may be life-threatening or fatal, can occur in patients receiving ELZONRIS. Monitor for signs and symptoms of CLS and take actions as recommended

WARNINGS AND PRECAUTIONS

Capillary Leak Syndrome

  • ELZONRIS can cause capillary leak syndrome (CLS), which may be life-threatening or fatal if not properly managed. The overall incidence of CLS in clinical trials was 55% in patients receiving ELZONRIS, including 46% in Grades 1 or 2, 6% in Grade 3, 1% in Grade 4, and 2 fatal events. Common signs and symptoms (incidence ≥ 20%) associated with CLS that were reported during treatment with ELZONRIS include hypoalbuminemia, edema, weight gain, and hypotension
  • Before initiating therapy with ELZONRIS, ensure that the patient has adequate cardiac function and serum albumin is ≥ 3.2 g/dL
  • During treatment with ELZONRIS, ensure that serum albumin levels are ≥ 3.5 g/dL and have not been reduced by ≥ 0.5 g/dL from the albumin value measured prior to dosing initiation of the current cycle. Monitor serum albumin levels prior to the initiation of each dose or more often as indicated clinically thereafter. Additionally, assess patients for other signs or symptoms of CLS, including weight gain, new onset or worsening edema including pulmonary edema, hypotension, or hemodynamic instability
  • Counsel patients to seek immediate medical attention should signs or symptoms of CLS occur at any time

Hypersensitivity Reactions

  • ELZONRIS can cause severe hypersensitivity reactions. Grade 3 or higher events were reported in 10% of patients in clinical trials. Monitor patients for hypersensitivity reactions during treatment with ELZONRIS. Interrupt ELZONRIS infusion and provide supportive care as needed if a hypersensitivity reaction should occur. If the reaction is severe, discontinue ELZONRIS permanently

Hepatotoxicity

  • Elevations in liver enzymes can occur with ELZONRIS. Grade 3 or higher elevations in liver enzymes occurred in approximately 40% of patients in clinical trials
  • Monitor alanine aminotransferase (ALT) and aspartate aminotransferase (AST) prior to each infusion with ELZONRIS. Temporarily withhold ELZONRIS if the transaminases rise to greater than 5 times the upper limit of normal (ULN) and resume treatment upon normalization or when resolved

ADVERSE REACTIONS:

The most common adverse reactions in the clinical trials (incidence ≥ 30%) are capillary leak syndrome, nausea, fatigue, peripheral edema, pyrexia, and weight increase. The most common laboratory abnormalities (incidence ≥ 50%) are decreases in albumin, platelets, hemoglobin, calcium, sodium, and increases in glucose, ALT, and AST.


Please see full Prescribing Information, including Boxed WARNING.


To report SUSPECTED ADVERSE REACTIONS, contact Stemline Therapeutics, Inc. at 1-877-332-7961 or contact the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

IMPORTANT SAFETY INFORMATION

INDICATION

  • ELZONRIS is a CD123-directed cytotoxin for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and in pediatric patients 2 years and older

IMPORTANT SAFETY INFORMATION

Boxed WARNING: CAPILLARY LEAK SYNDROME

  • Capillary Leak Syndrome (CLS), which may be life-threatening or fatal, can occur in patients receiving ELZONRIS. Monitor for signs and symptoms of CLS and take actions as recommended

WARNINGS AND PRECAUTIONS

Capillary Leak Syndrome

  • ELZONRIS can cause capillary leak syndrome (CLS), which may be life-threatening or fatal if not properly managed. The overall incidence of CLS in clinical trials was 55% in patients receiving ELZONRIS, including 46% in Grades 1 or 2, 6% in Grade 3, 1% in Grade 4, and 2 fatal events. Common signs and symptoms (incidence ≥ 20%) associated with CLS that were reported during treatment with ELZONRIS include hypoalbuminemia, edema, weight gain, and hypotension
  • Before initiating therapy with ELZONRIS, ensure that the patient has adequate cardiac function and serum albumin is ≥ 3.2 g/dL
  • During treatment with ELZONRIS, ensure that serum albumin levels are ≥ 3.5 g/dL and have not been reduced by ≥ 0.5 g/dL from the albumin value measured prior to dosing initiation of the current cycle. Monitor serum albumin levels prior to the initiation of each dose or more often as indicated clinically thereafter. Additionally, assess patients for other signs or symptoms of CLS, including weight gain, new onset or worsening edema including pulmonary edema, hypotension, or hemodynamic instability
  • Counsel patients to seek immediate medical attention should signs or symptoms of CLS occur at any time

Hypersensitivity Reactions

  • ELZONRIS can cause severe hypersensitivity reactions. Grade 3 or higher events were reported in 10% of patients in clinical trials. Monitor patients for hypersensitivity reactions during treatment with ELZONRIS. Interrupt ELZONRIS infusion and provide supportive care as needed if a hypersensitivity reaction should occur. If the reaction is severe, discontinue ELZONRIS permanently

Hepatotoxicity

  • Elevations in liver enzymes can occur with ELZONRIS. Grade 3 or higher elevations in liver enzymes occurred in approximately 40% of patients in clinical trials
  • Monitor alanine aminotransferase (ALT) and aspartate aminotransferase (AST) prior to each infusion with ELZONRIS. Temporarily withhold ELZONRIS if the transaminases rise to greater than 5 times the upper limit of normal (ULN) and resume treatment upon normalization or when resolved

ADVERSE REACTIONS:

The most common adverse reactions in the clinical trials (incidence ≥ 30%) are capillary leak syndrome, nausea, fatigue, peripheral edema, pyrexia, and weight increase. The most common laboratory abnormalities (incidence ≥ 50%) are decreases in albumin, platelets, hemoglobin, calcium, sodium, and increases in glucose, ALT, and AST.


Please see full Prescribing Information, including Boxed WARNING.


To report SUSPECTED ADVERSE REACTIONS, contact Stemline Therapeutics, Inc. at 1-877-332-7961 or contact the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.