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Who's a Proleukin Candidate?

Which patients may benefit the most from Proleukin?

A patient’s overall health status is an extremely important factor in identifying your adult mRCC or mM patients who may benefit the most from Proleukin. Overall health status has been shown to correlate with how well patients will respond to Proleukin. Nearly all the patients in the pivotal Proleukin clinical trials had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.1,2,*

Both younger and older patients may be candidates for Proleukin

A patient’s physiological age may actually be younger (or older) than their calendar age. Performance status is determined by multiple physiological factors, and age should not be a limiting factor when considering treatment with Proleukin.3 Of those patients who experienced a durable complete response in the Proleukin clinical trials, their age at treatment varied by decades.1,2

What does ECOG PS 0 or 1 mean?
  • PS 0: patient is fully active and able to carry on all predisease performance without restriction4,5
  • PS 1: patient is restricted in physically strenuous activity, but ambulatory, and is able to carry out work of a light or sedentary nature (eg, light housework, office work)4,5
Setting patient's treatment schedule expectations

With Proleukin, patients should expect to commit to (typically) two 5-day treatment cycles in a specialized IL-2 Treatment Center, with 9 days of rest in between.3

Does your patient have other serious health problems?

Only patients with normal cardiac and pulmonary functions should receive Proleukin. The checklist below provides important patient selection considerations that can make all the difference with Proleukin.

Careful patient selection is mandatory prior to the administration of Proleukin. Please see “CONTRAINDICATIONS,” “WARNINGS,” and “PRECAUTIONS” sections in the full Prescribing Information, regarding patient screening, including recommended cardiac and pulmonary function tests and laboratory tests.

*mRCC: PS 0 = 65% and PS 1 = 31%; mM: PS 0 = 71% and PS 1 = 27%.1,2

The Path to Proleukin Patient Selection and Treatment

1.

Adult mRCC or mM patients with ECOG PS of 0 or 1.a

2.

No:
active CNSb metastases, organ transplants, autoimmune diseases, inflammatory disorders, infection.

3.

Patient is referred to a specialized IL-2 Treatment Center.

4.

Patient is referred to a specialized IL-2 Treatment Center.

5.

Proleukin treatment cycle 1 is administered over 5 days.c

6.

Patient rests at home for about 9 days.

7.

Proleukin treatment cycle 2 is administered over 5 days.c

aOr an equivalent Karnofsky score.
bCNS = Central nervous system.
cTreatment with Proleukin is typically based on two 5-day cycles that constitute 1 course of therapy, with 9 days of rest in between. Patients who respond to Proleukin can go on to receive additional courses, while nonresponders are typically eligible for other treatment options.3

Checklist

Use this checklist to help determine if Proleukin may be right for your patients. If you check all the boxes, consider referring your patient to a specialized IL-2 Treatment Center for Proleukin therapy.

PERFORMANCE STATUS:
  • ECOG PS of 0 or 1,3 or an equivalent Karnofsky score
NEGATIVE FOR3:
  • Active central nervous system (CNS) metastases
  • Any organ transplant
  • Autoimmune diseases, including scleroderma, bullous pemphigoid, and myasthenia gravis
  • Inflammatory disorders, including Crohn’s disease, inflammatory arthritis, and thyroiditis
  • Infection
ORGAN FUNCTION:
  • Pulmonary: FEV1 > 2 liters or ≥ 75% of predicted for height and age3
  • Cardiac: normal ejection fraction and unimpaired wall motion on thallium stress test3
  • Renal: serum creatinine ≤ 1.5 mg/dL and creatinine clearance > 60 mL/min3,6
  • Hepatic: bilirubin ≤ 2 mg/dL7
  • CNS: normal CNS function3

References: 1. Fyfe G, Fisher RI, Rosenberg SA, Sznol M, Parkinson DR, Louie AC. Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. J Clin Oncol. 1995;13(3):688-696. 2. Atkins MB, Lotze MT, Dutcher JP, et al. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol. 1999;17(7):2105-2116. 3. Proleukin [package insert]. Yardley, PA: Clinigen, Inc; 2019. 4. Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5(6):649-655. 5. Sørensen JB, Klee M, Palshof T, Hansen HH. Performance status assessment in cancer patients. An inter-observer variability study. Br J Cancer. 1993;67(4):773-775. 6. Jarkowski A III, Wong MKK. A re-assessment of the safety and efficacy of interleukin-2 for the treatment of renal cell carcinoma. Clin Med Ther. 2009;1:527-540. 7. Schwartzentruber DJ. Guidelines for the safe administration of high-dose interleukin-2. J Immunother. 2001;24(4):287-293.

EXPAND +

Proleukin® (aldesleukin) is indicated for the treatment of adults with metastatic melanoma (mM) and metastatic renal cell carcinoma (mRCC).

Summary of Important Safety Information for Proleukin® (aldesleukin) for injection, for intravenous infusion.

Proleukin® (aldesleukin) is indicated for the treatment of adults with metastatic melanoma (mM) and metastatic renal cell carcinoma (mRCC).

Summary of Important Safety Information for Proleukin® (aldesleukin) for injection, for intravenous infusion.

WARNINGS

Therapy with Proleukin® (aldesleukin) should be restricted to patients with normal cardiac and pulmonary functions as defined by thallium stress testing and formal pulmonary function testing. Extreme caution should be used in patients with a normal thallium stress test and a normal pulmonary function test who have a history of cardiac or pulmonary disease.

Proleukin should be administered in a hospital setting under the supervision of a qualified physician experienced in the use of anticancer agents. An intensive care facility and specialists skilled in cardiopulmonary or intensive care medicine must be available.

Proleukin administration has been associated with capillary leak syndrome (CLS) which is characterized by a loss of vascular tone and extravasation of plasma proteins and fluid into the extravascular space. CLS results in hypotension and reduced organ perfusion which may be severe and can result in death. CLS may be associated with cardiac arrhythmias (supraventricular and ventricular), angina, myocardial infarction, respiratory insufficiency requiring intubation, gastrointestinal bleeding or infarction, renal insufficiency, edema, and mental status changes.

Proleukin treatment is associated with impaired neutrophil function (reduced chemotaxis) and with an increased risk of disseminated infection, including sepsis and bacterial endocarditis. Consequently, preexisting bacterial infections should be adequately treated prior to initiation of Proleukin therapy. Patients with indwelling central lines are particularly at risk for infection with gram positive microorganisms. Antibiotic prophylaxis with oxacillin, nafcillin, ciprofloxacin, or vancomycin has been associated with a reduced incidence of staphylococcal infections.

Proleukin administration should be withheld in patients developing moderate to severe lethargy or somnolence; continued administration may result in coma.

INDICATION AND USAGE

Proleukin® (aldesleukin) is indicated for the treatment of adults with metastatic renal cell carcinoma (metastatic RCC).

Proleukin is indicated for the treatment of adults with metastatic melanoma.

Careful patient selection is mandatory prior to the administration of Proleukin.

Evaluation of clinical studies to date reveals that patients with more favorable ECOG performance status (ECOG PS 0) at treatment initiation respond better to Proleukin, with a higher response rate and lower toxicity. Therefore, selection of patients for treatment should include assessment of performance status.

Experience in patients with ECOG PS > 1 is extremely limited.

CONTRAINDICATIONS

Proleukin® (aldesleukin) is contraindicated in patients with a known history of hypersensitivity to interleukin-2 or any component of the Proleukin formulation.

Proleukin is contraindicated in patients with an abnormal thallium stress test or abnormal pulmonary function tests and those with organ allografts. Retreatment with Proleukin is contraindicated in patients who have experienced the following drug-related toxicities while receiving an earlier course of therapy: sustained ventricular tachycardia (≥ 5 beats), cardiac arrhythmias not controlled or unresponsive to management, chest pain with ECG changes, consistent with angina or myocardial infarction, cardiac tamponade, intubation for > 72 hours, renal failure requiring dialysis > 72 hours, coma or toxic psychosis lasting > 48 hours, repetitive or difficult to control seizures, bowel ischemia/perforation, GI bleeding requiring surgery.

WARNINGS

Because of the severe adverse events which generally accompany Proleukin® (aldesleukin) therapy at the recommended dosages, thorough clinical evaluation should be performed to identify patients with significant cardiac, pulmonary, renal, hepatic, or CNS impairment in whom Proleukin is contraindicated. Patients with normal cardiovascular, pulmonary, hepatic, and CNS function may experience serious, life-threatening or fatal adverse events. Adverse events are frequent, often serious, and sometimes fatal.

Should adverse events, requiring dose modification occur, dosage should be withheld rather than reduced.

Proleukin has been associated with exacerbation of preexisting autoimmune disease and inflammatory disorders. In some cases, the onset of new autoimmune diseases, such as vitiligo, may occur. Symptomatic hyperglycemia and/or diabetes mellitus have been reported during Proleukin therapy.

All patients should have thorough evaluation and treatment of CNS metastases and have a negative scan prior to receiving Proleukin therapy. New neurologic signs, symptoms, and anatomic lesions following Proleukin therapy have been reported in patients without evidence of CNS metastases. Neurologic signs and symptoms associated with Proleukin therapy usually improve after discontinuation of Proleukin therapy; however, there are reports of permanent neurologic defects. In patients with known seizure disorders, extreme caution should be exercised as Proleukin may cause seizures.

PRECAUTIONS

Patients should have normal cardiac, pulmonary, hepatic, and CNS function at the start of therapy. Capillary leak syndrome (CLS) begins immediately after Proleukin® (aldesleukin) treatment starts and is marked by increased capillary permeability to protein and fluids and reduced vascular tone.

Proleukin® (aldesleukin) treatment should be withheld for failure to maintain organ perfusion as demonstrated by altered mental status, reduced urine output, a fall in the systolic blood pressure below 90 mm Hg or onset of cardiac arrhythmias.

Recovery from CLS begins soon after cessation of Proleukin therapy. Usually, within a few hours, the blood pressure rises, organ perfusion is restored and reabsorption of extravasated fluid and protein begins.

Kidney and liver function are impaired during Proleukin treatment. Use of concomitant nephrotoxic or hepatotoxic medications may further increase toxicity to the kidney or liver.

Mental status changes including irritability, confusion, or depression which occur while receiving Proleukin may be due to bacteremia or early bacterial sepsis, hypoperfusion, occult CNS malignancy, or direct Proleukin-induced CNS toxicity. Patients should be evaluated for these and other causes of mental status changes. Alterations in mental status due solely to Proleukin therapy may progress for several days before recovery begins. Rarely, patients have sustained permanent neurologic deficits.

Proleukin enhancement of cellular immune function may increase the risk of allograft rejection in transplant patients.

Serious manifestations of eosinophilia involving eosinophilic infiltration of cardiac and pulmonary tissues can occur following Proleukin.

ADVERSE REACTIONS

The rate of drug-related deaths in the 255 metastatic RCC patients who received single-agent Proleukin® (aldesleukin) was 4% (11/255); the rate of drug-related deaths in the 270 metastatic melanoma patients who received single-agent Proleukin was 2% (6/270).

In clinical trials, the following life-threatening (Grade 4) adverse events were seen in > 1% of 525 patients (255 with metastatic renal cell cancer and 270 with metastatic melanoma) treated with Proleukin: oliguria (6%), anuria (5%), hypotension (3%), respiratory disorder (3%), bilirubinemia (2%), coma (2%), diarrhea (2%), acidosis (1%), acute kidney failure (1%), apnea (1%), cardiovascular disorder (1%), coagulation disorders (1%), confusion (1%), creatinine increase (1%), dyspnea (1%), fever (1%), heart arrest (1%), infection (1%), myocardial infarction (1%), psychosis (1%), sepsis (1%), SGOT increase (1%), stupor (1%), supraventricular tachycardia (1%), thrombocytopenia (1%), ventricular tachycardia (1%), and vomiting (1%). From the same trials, the following adverse events (Grades 1-4) were seen in ≥ 30% of 525 patients (255 with metastatic renal cell cancer and 270 with metastatic melanoma) treated with Proleukin: hypotension (71%), diarrhea (67%), oliguria (63%), chills (52%), vomiting (50%), dyspnea (43%), rash (42%), bilirubinemia (40%), thrombocytopenia (37%), nausea (35%), confusion (34%), and creatinine increase (33%).

Please see the full Prescribing Information, including Boxed Warning, for Proleukin® (aldesleukin) for injection, for intravenous infusion.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

The content contained in this website is not intended to be a substitute for professional medical advice related to any topic discussed. Patients are urged to consult with their treating physicians or other professionals. Never disregard professional, medical, or legal advice or delay seeking such advice because of something you have read on this website.