Low-dose interleukin-2 immunotherapy does not improve outcome of patients age 60 years and older with acute myeloid leukemia in first complete remission: Cancer and Leukemia Group B Study 9720

J Clin Oncol. 2008 Oct 20;26(30):4934-9. doi: 10.1200/JCO.2008.17.0472. Epub 2008 Jun 30.

Abstract

Purpose: Cancer and Leukemia Group B (CALGB) 9720 evaluated subcutaneous low-dose recombinant interleukin-2 (rIL-2) maintenance immunotherapy as a strategy for prolonging remission in older patients with acute myeloid leukemia (AML).

Patients and methods: AML patients age 60 years and older in first complete remission after induction and consolidation chemotherapy were randomly assigned to no further therapy or a 90-day regimen of 14-day cycles of low-dose rIL-2, aimed at expanding natural killer (NK) cells, followed by 3-day higher doses aimed at activating cytotoxicity of expanded NK cells to lyse residual AML cells. All randomly assigned patients were included in an intention-to-treat analysis.

Results: A total of 163 (64%) of 254 patients who completed induction and consolidation chemotherapy on CALGB 9720 were randomly assigned to rIL-2 (n = 81) or no further therapy (n = 82); the most common reasons for lack of random assignment were patient refusal and relapse. Fifteen patients randomly assigned to rIL-2 never initiated it because of refusal, intercurrent medical problems, or relapse, and 24 patients initiated rIL-2 but stopped early because of toxicity or relapse. Grade 4 toxicities during rIL-2 therapy included thrombocytopenia (65%) and neutropenia (64%), and grade 3 toxicities included anemia (33%), infection (24%) and malaise/fatigue (14%). Forty-two patients (52%) randomly assigned to rIL-2 completed the full 90-day course. Patients in both arms had similar distributions of both disease-free (combined median = 6.1 months; P = .47) and overall survival (combined median = 14.7 months; P = .61) after random assignment. Moreover, the 42 patients who completed all planned therapy did not show prolongation of disease-free or overall survival.

Conclusion: Low-dose rIL-2 maintenance immunotherapy is not a successful strategy in older AML patients.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Disease-Free Survival
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Immunotherapy
  • Interleukin-2 / therapeutic use*
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / mortality*
  • Male
  • Middle Aged
  • Remission Induction
  • Survival Rate
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Interleukin-2