Download the CLS Management Guide for a quick reference on how to manage CLS.
Download the CLS On-Demand Deck for presentation slides with detailed guidance on how to manage CLS.
A CLS Alert Kit is available to healthcare professionals treating and monitoring patients receiving ELZONRIS on an inpatient or outpatient basis, indicating that the patient is a "CAPILLARY LEAK SYNDROME RISK." Kit contains patient alert bracelet, alert sign (to be placed in inpatient room), and chart sticker.
Summary of CLS in clinical trials
Common signs and symptoms associated with CLS that were reported during treatment with ELZONRIS include1:
- Hypoalbuminemia
- Edema, including pulmonary edema
- Weight gain
- Hypotension
- Hemodynamic instability
CLS incidence in patients receiving ELZONRIS in clinical trials1
Overall incidence of CLS was 53% (65/122)
- 43% incidence of Grade 1 or 2 events (52/122)
- 7% incidence of Grade 3 events (8/122)
- 1% incidence of Grade 4 events (1/122)
- 3% incidence of Grade 5 events (4/122)
Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, life-threatening; Grade 5, death.
CLS was managed per recommended CLS management guidelines described below and in Table 2 of the full Prescribing Information.
CLS assessment criteria for patients on ELZONRIS1
Assess all patients appropriately before and throughout ELZONRIS treatment1
- Before initiating therapy with ELZONRIS (first dose of first cycle):
- Ensure patients have adequate cardiac function*
- Ensure patients have serum albumin ≥3.2 g/dL
- Weigh patients to establish baseline weight for subsequent dose
- During treatment with ELZONRIS:
- Monitor serum albumin levels prior to the initiation of each dose of ELZONRIS and as clinically indicated thereafter
- Assess patients for signs/symptoms of CLS, including:
- Weight gain ≥1.5 kg from the previous day's predose weight
- New onset or worsening edema, including pulmonary edema
- Hypotension or hemodynamic instability
- Serum albumin <3.5 g/dL or reduced by ≥0.5 g/dL from the albumin value measured prior to ELZONRIS dosing initiation of the current cycle
Observe patients during ELZONRIS administration1
- Cycle 1
- The first cycle must be administered in the inpatient setting
Observe patients for at least 24 hours after the last infusion of the first cycle
- The first cycle must be administered in the inpatient setting
- Subsequent cycles
- Subsequent cycles may be administered in an inpatient setting or an appropriate outpatient setting
Counsel patients upon discharge1
- Advise patients of the risk of CLS, and to contact their healthcare provider for signs and symptoms associated with CLS, including new or worsening edema, weight gain, shortness of breath, and/or hypotension after infusion. Advise patients to weigh themselves daily
*In clinical studies, patients had a left ventricular ejection fraction ≥ institutional lower limit of normal as measured by multigated acquisition scan or 2-dimensional echocardiography within 28 days prior to start of therapy and no clinically significant abnormalities on a 12-lead electrocardiogram.2
Guidance for CLS management in patients1
Management of CLS is an important part of treating patients with BPDCN with ELZONRIS.
- 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 | Administer ELZONRIS when serum albumin |
||
| During ELZONRIS dosing | Administer 25 g 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 | Interrupt ELZONRIS dosing until the relevant CLS sign/ symptom has resolved† | |
| Serum albumin |
|||
| A predose body weight that is increased by |
Administer 25 g intravenous albumin (q12h or more frequently as practical) and manage fluid status as clinically indicated (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 clinically indicated Aggressive 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 |
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†ELZONRIS dose is held1:
- ELZONRIS 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
BPDCN, blastic plasmacytoid dendritic cell neoplasm; q12h, every 12 hours.
- References:
- ELZONRIS [prescribing information]. New York, NY: Stemline Therapeutics, Inc.; November 2022.
- Data on file. Stemline Therapeutics, Inc.