Efficacy and safety of OK-432 immunotherapy of lymphatic malformations

Authors

  • Mark C. Smith MD,

    1. Division of Otolaryngology–Head and Neck Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire
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  • M. Bridget Zimmerman PhD,

    1. Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa
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  • Diane K. Burke RN, BSN,

    1. Department of Otolaryngology–Head and Neck Surgery, The University of Iowa, Iowa City, Iowa, U.S.A.
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  • Nancy M. Bauman MD,

    1. Department of Otolaryngology–Head and Neck Surgery, The University of Iowa, Iowa City, Iowa, U.S.A.
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  • Yutaka Sato MD,

    1. Department of Radiology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, U.S.A.
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  • Richard J. H. Smith MD,

    Corresponding author
    1. Department of Otolaryngology–Head and Neck Surgery, The University of Iowa, Iowa City, Iowa, U.S.A.
    • Department of Otolaryngology–Head and Neck Surgery, University of Iowa Hospitals and Clinics, 200 Hawkins Dr, 21151-A, Iowa City, IA, 52242-1078
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  • the OK-432 Collaborative Study Group

    1. Division of Otolaryngology–Head and Neck Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire
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    • *

      OK-432 Collaborative Study Group: 1. Alabama–Children's Hospital of Alabama, Birmingham: Keith Georgeson, MD, Beverly Haynes, RN; 2. Arizona–St. Joseph's Hospital, Phoenix: Edward Joganic, MD; 3. California–Rady Children's Hospital, San Diego: Anthony Magit, MD, Seth Pransky, MD, Candace Lee, RN; Children's Hospital of Central California, Madera: Elizabeth Pohlson, MD; 4. Colorado–The Children's Hospital, Aurora: Peggy Kelley, MD, Mary Carol Cryer, RN; 5. Delaware–Dupont Children's Hospital, Wilmington: Steven Cook, MD; 6. District of Columbia–Children's National Medical Center, Washington, D.C.: Nancy Bauman, MD; 7. Florida–Nemours Children's Clinic, Jacksonville: Gary Josephson, MD; All Children's Hospital, St. Petersburg: Thomas Andrews, MD, Susan Bryan, RN; 8. Hawaii–Kapiolani Medical Center, Honolulu: Daniel Robie, MD; 9. Iowa–University of Iowa Hospitals and Clinics, Iowa City: Jose Manaligod, MD, Richard J.H. Smith, MD, Diane Burke, RN; 10. Massachusetts–Children's Hospital, Boston: Patricia Burrows, MD; 11. Minnesota–Children's Hospitals and Clinics of Minnesota, Minneapolis: Bruce Bostrom, MD, Elizabeth McDonough, RN; 12. Missouri–University of Kansas Medical Center, Kansas City: Daniel Bruegger, MD; 13. New York–SUNY Upstate Medical Center, Syracuse: Anthony Mortelliti, MD, Amar Swarnkar, MD, Kelly Winchell, RN; New York Medical Center, New York: Francine Blei, MD; 14. Oregon–Oregon Health Sciences University, Portland: Henry Milczuk, MD, Mark Richardson, MD; 15. Pennsylvania–Thomas Jefferson University, Philadelphia: Louis Lowry, MD; Children's Hospital: Ian Jacobs, MD; 16. Texas–Children's Ear, Nose and Throat of Houston, Houston: Joseph Edmonds, MD, Susan Griffin, RN; University of Texas Southwestern, Dallas: Michael Biavati, MD, Nancy Rollins, MD; Capital Otolaryngology, Austin: Zachary Wassmuth, MD; 17. Virginia–Children's Hospital of the Kings Daughter, East Virginia Medical School, Norfolk: Craig Derkay, MD, Lorrie Coggsdale, RN; 18. Washington–Children's Hospital Medical Center, Seattle: Scott Manning, MD; 19. Wisconsin–Children's Hospital of Wisconsin, Milwaukee: Joseph Kerschner, MD, Roxanne Link, RN; American Family Children's Hospital, Madison: Scott McMurray, MD, Kari McConnell, RN, Nadine Connor, PhD.


  • This study was supported in part by FD-R-001774 (RJHS). Chugai Pharmaceutical Co., Ltd., Japan provided the OK-432 used in this study at no cost and also provided partial salary support to DKB during study period.

Abstract

Objectives:

To determine the efficacy and safety of the immunostimulant OK-432 (Picibanil) as a treatment option in the management of children with cervicofacial lymphatic malformations.

Study Design:

A prospective, randomized, multi-institutional phase II clinical trial at 27 U.S. academic medical centers.

Methods:

182 patients with lymphatic malformations (LM) were enrolled between January 1998 and November 2004. Of the 151 patients with complete case report forms, 117 patients were randomized into immediate or delayed treatment groups; 34 patients were nonrandomized and assigned to the open-label group. Treatment consisted of a four-dose intralesional injection series of OK-432 at eight-week intervals. Patients randomized into the delayed treatment group served as observational controls for spontaneous regression. Response to therapy was measured radiographically by quantitating change in lesion size and graded as complete (90%–100%), substantial (60%–89%), intermediate (20%–59%), or none (<20%).

Results:

Of 117 patients randomized with intent-to-treat, 68% demonstrated a complete or substantial response to OK-432 immunotherapy. Response data for macrocystic LM were higher, with a complete or substantial response in 94% of patients; 63% of patients with mixed macrocystic-microcystic LM responded to treatment; no patients with microcystic LM responded to treatment. Spontaneous resolution occurred in less than 2% of patients. Median follow-up of 2.9 years demonstrated a 9% recurrence rate. Major adverse effects related to therapy occurred in 11 patients. As compared to historical surgical data on LM, OK-432 immunotherapy is more effective (P < .001) and has a lower morbidity (P < .001).

Conclusions:

OK-432 immunotherapy is an effective, safe, and simple treatment option for the management of macrocystic cervicofacial LM.

Trial Registration:

ClinicalTrials.gov Identifier: NCT00010452. Laryngoscope, 119:107–115, 2009

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