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Acute Morbidity and Mortality after High Dose IL-2 Treatment in Patients with Metastatic Melanoma

Acute Morbidity and Mortality after High Dose IL-2 Treatment in Patients with Metastatic Melanoma. Laura Miars, PharmD PGY-2 Hematology/Oncology Resident Huntsman Cancer Institute/University of Utah. Melanoma: Epidemiology and Risk Factors. 68,000 new cases and 8,600 deaths in 2009

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Acute Morbidity and Mortality after High Dose IL-2 Treatment in Patients with Metastatic Melanoma

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  1. Acute Morbidity and Mortality after High Dose IL-2 Treatment in Patients with Metastatic Melanoma Laura Miars, PharmD PGY-2 Hematology/Oncology Resident Huntsman Cancer Institute/University of Utah

  2. Melanoma: Epidemiology and Risk Factors • 68,000 new cases and 8,600 deaths in 2009 • Average age at diagnosis is 59 years • Risk factors • Prior melanoma/family history • Intermittent, high-intensity UV light exposure • Others www.cancer.org, N Engl J Med 2006:355:51-65, Mayo Clin Proc 2006;81:500-507, NCCN Clinical Practice Guidelines in Oncology: Melanoma. Version 2.2010

  3. Staging and Treatment www.cancer.org, N Engl J Med 2006:355:51-65, Mayo Clin Proc 2006;81:500-507, NCCN Clinical Practice Guidelines in Oncology: Melanoma. Version 2.2010

  4. Staging and Treatment www.cancer.org, N Engl J Med 2006:355:51-65, Mayo Clin Proc 2006;81:500-507, NCCN Clinical Practice Guidelines in Oncology: Melanoma. Version 2.2010

  5. High Dose IL-2 • Mechanism: immune modulation, T-cell growth factor, cytokine release • Usual dose range • 600,000 to 720,000 units/kg/dose • Administration • IV bolus every 8 hours x 14 doses • Days 1-5 and 15-19 (28 doses/cycle); repeat every 6-12 weeks JAMA 1994:271:907-913, J Clin Oncol 1999;17:2105-2116, J Immunother 2001;24: 287-293, NCCN Clinical Practice Guidelines in Oncology: Melanoma. Version 2.2010

  6. High Dose IL-2 • Efficacy: 16% response rate • 6% complete response • 10% partial response • Toxicity (morbidity) • Capillary leak syndrome: cardiac, GI, pulmonary, renal, altered mental status • Bone marrow suppression • Constitutional symptoms JAMA 1994:271:907-913, J Clin Oncol 1999;17:2105-2116, J Immunother 2001;24: 287-293, NCCN Clinical Practice Guidelines in Oncology: Melanoma. Version 2.2010

  7. IL-2 Protocols at Huntsman Cancer Hospital JAMA 1994:271:907-913, J Clin Oncol 1999;17:2105-2116

  8. Research Objectives • Primary objectives: in-hospital mortality, percent of patients requiring transfer to intensive care unit • Secondary objectives (morbidity) • Elevation of serum creatinine and bilirubin • Cardiac arrhythmias • Weight gain • Other: number of IL-2 doses, number of IL-2 courses, length of hospital stay JAMA 1994:271:907-913, J Clin Oncol 1999;17:2105-2116

  9. Study Design • Retrospective case-series • 2003-2010 • Two patient dose groups • Data collection • Toxicity grading: Common Terminology Criteria for Adverse Events, Version 3.0 • Statistical Analysis • Descriptive statistics Cancer Therapy Evaluation Program, Common Terminology Criteria for Adverse Events, Version 3.0, DCTD, NCI, NIH, DHHS March 31, 2003. Publish Date: August 9, 2006

  10. Patient Selection Criteria • Inclusion • Greater than 18 years of age • Diagnosed with metastatic melanoma • Admitted for high dose IL-2 therapy • 600,000 or 720,000 units/kg/dose • Exclusion • IL-2 with other dosing or for other reason besides melanoma JAMA 1994:271:907-913, J Clin Oncol 1999;17:2105-2116

  11. Patient Characteristics kg = kilograms, BMI = body mass index, ABW = actual body weight, IBW = ideal body weight J Clin Oncol 1999;17:2105-2116, www.americanheart.org

  12. Primary Objectives *Atkins, MB et al. J Clin Oncol 1999;17:2105-2116

  13. Toxicities *Patients admitted twice per IL-2 course, Days 1-5 and Days 15-19; VT = ventricular tachycardia, ST = sinus tachycardia

  14. Other Secondary Objectives kg = kilogram, LOS = length of stay, MU = millions of units, ABW = actual body weight

  15. Other Observations • Dose-limiting toxicities in 720,000 units/kg/dose group • Large volume diarrhea (15%) • Transient liver toxicity (7%) • Transient neurologic toxicity (45%) • Allergies developed to nafcillin in 720,000 units/kg/dose group • 40% (6/15 patients)

  16. Study Limitations • Retrospective data collection • Incomplete nursing documentation • Small sample size

  17. Conclusions • Comparable mortality and toxicities • Trends in 720,000 units/kg/dose group • Increased diarrhea, neurologic, and liver toxicities as dose-limiting toxicities • Increased antibiotic allergies • No difference in length of stay or cumulative IL-2 exposure, but increased toxicity with 720,000 units/kg/dose regimen

  18. Future Directions • Changes in practice • Decreasing dose to 600,000 units/kg/dose • No antibiotic prophylaxis • Presentation to nursing staff • Ideal, adjusted, or actual body weight?

  19. Acute Morbidity and Mortality after High Dose IL-2 Treatment in Patients with Metastatic Melanoma Laura Miars, PharmD PGY-2 Hematology/Oncology Resident Huntsman Cancer Institute/University of Utah

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