Prolonged administration of low-dose interleukin-2 in human immunodeficiency virus-associated malignancy results in selective expansion of innate immune effectors without significant clinical toxicity

  • Bernstein Z
  • Porter M
  • Gould M
 et al. 
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Abstract

Ten adult patients with human immunodeficiency virus (HIV)-associated malignancies (five with lymphoma and five with Kaposi's Sarcoma) were treated with a daily subcutaneous injection of interleukin-2 (IL-2) for 90 consecutive days in a phase I dose-escalation study. Seven patients had absolute CD4 counts below 200/mm3 at the time malignancy was diagnosed. Each lymphoma patient had obtained a complete or partial remission with standard chemotherapy before initiating IL-2. The daily dose of IL-2 did not change during the 90-day course of therapy. Seventeen courses of IL-2 therapy were completed at doses ranging from 0.4 x 10(6) U/m2/d to 1.2 x 10(6) U/m2/d without significant (grade III) toxicity. Two of two patients experienced grade III toxicity within 21 days of initiating IL-2 at a dose of 1.4 x 10(6) U/m2/d, but both patients subsequently completed 90 days of therapy at the maximum tolerated dose (MTD) of 1.2 x 10(6) U/m2/d. Although there were no significant increases or decreases in T-cell subsets at any dose level, there was an increase in absolute natural killer (NK) cell number at the three highest doses of IL-2 (mean percent increase 247; 95% confidence interval, 124 to 369) that was statistically significant (Wilcoxon one-sample signed rank test, P = .015). One patient developed an anti-IL-2 antibody titer that correlated with minimal NK cell expansion in vitro and in vivo. An increase in eosinophils was noted during 9 of 17 courses of IL-2 therapy without correlation to IL-2 dose, prior course of IL-2, or NK cell expansion. At the MTD, there was no consistent increase in the plasma HIV RNA level over time. Three of 10 patients had progressive disease while on study. During 50 months of IL-2 therapy, no patient was treated for an opportunistic infection. We conclude that daily low dose subcutaneous IL-2 can be self-administered safely with good compliance for prolonged periods of time to patients with HIV-associated malignancies, including those with profound immune deficiency. The majority of patients show selective expansion of innate immune effectors, ie, NK cells and/or eosinophils, in the absence of significant clinical toxicity or increased viral burden. These results suggest that low-dose IL-2 therapy should be studied further in phase II clinical trials for evidence of activity against malignancy and opportunistic infection in this patient population

Author-supplied keywords

  • 10
  • AIDS-Related
  • AIDS-Related: immunology
  • AIDS-Related: therapy
  • Adult
  • Antibodies
  • Cells
  • Clinical Trials
  • Disease
  • Drug Administration Schedule
  • Eosinophils
  • Eosinophils: immunology
  • HIV Infections
  • HIV Infections: complications
  • Human immunodeficiency virus
  • Humans
  • IL-2
  • Immune
  • Immunologic Factors
  • Immunologic Factors: administration & dosage
  • Immunologic Factors: adverse effects
  • Immunologic Factors: therapeutic use
  • Immunotherapy
  • In vitro
  • In vivo
  • In-vitro
  • In-vivo
  • Infection
  • Injections
  • Interleukin-2
  • Interleukin-2: administration & dosage
  • Interleukin-2: adverse effects
  • Interleukin-2: therapeutic use
  • Kaposi
  • Kaposi: etiology
  • Kaposi: immunology
  • Kaposi: therapy
  • Killer Cells
  • Lymphoma
  • Male
  • Middle Aged
  • Natural
  • Natural: immunology
  • OR
  • Plasma
  • RNA
  • Recombinant Proteins
  • Recombinant Proteins: administration & dosage
  • Recombinant Proteins: adverse effects
  • Recombinant Proteins: therapeutic use
  • Sarcoma
  • Studies
  • Subcutaneous
  • T cell
  • Treatment Outcome
  • a
  • activity
  • and
  • antibody
  • antibody titer
  • cell
  • chemotherapy
  • clinical trial
  • confidence interval
  • deficiency
  • during
  • eosinophil
  • human
  • immune deficiency
  • immunodeficiency
  • in
  • innate
  • interleukin 2
  • level
  • natural
  • nk cells
  • no
  • of
  • opportunistic infection
  • patient
  • patients
  • phase i
  • population
  • remission
  • sarcoma
  • standard
  • the
  • therapy
  • time
  • to
  • toxicity
  • virus
  • with
  • x

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  • SCOPUS: 2-s2.0-0028840964
  • ISSN: 0006-4971
  • PUI: 25326025
  • SGR: 0028840964
  • ISBN: 0006-4971
  • PMID: 7579429

Authors

  • Z P Bernstein

  • M M Porter

  • M Gould

  • B Lipman

  • E M Bluman

  • C C Stewart

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