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Original paper
2003NEJMHematology/Oncology

IRIS

Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia

RCTChronic myeloid leukemia

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Overview

In newly diagnosed chronic-phase CML, imatinib produced higher cytogenetic response rates and less progression than interferon plus low-dose cytarabine.

Clinical takeaway

Start imatinib rather than interferon plus low-dose cytarabine for newly diagnosed chronic-phase CML. This report is about cytogenetic response, tolerability, and short-term progression, not overall survival.

Key result

Estimated major cytogenetic response at 18 months was 87.1% with imatinib versus 34.7% with interferon alfa plus cytarabine (P<0.001).

Practice impact

Imatinib replaced interferon-based induction as first-line therapy for newly diagnosed chronic-phase CML.

Evidence

Study design

Randomized comparison of imatinib with interferon alfa plus low-dose cytarabine, with crossover allowed for treatment failure or intolerance.

Enrollment

1,106

Follow-up

Median follow-up 19 months; cytogenetic and progression estimates reported at 18 months.

Geography

Not listed

Clinical question

Is imatinib better than interferon alfa plus low-dose cytarabine as first-line therapy for newly diagnosed chronic-phase CML?

Population

  • Patients with newly diagnosed chronic-phase chronic myeloid leukemia.

Intervention

Imatinib (553 patients). The abstract does not state the dose.

Comparator

Interferon alfa plus low-dose cytarabine (553 patients). The abstract does not state the doses.

Primary outcome

Hematologic and cytogenetic responses, toxic effects, and rates of progression. A single named primary end point is not stated.

Estimated major cytogenetic response at 18 months was 87.1% with imatinib versus 34.7% with interferon alfa plus cytarabine.

p<0.001

Key results

  • Estimated major cytogenetic response (0 to 35% of metaphase cells Philadelphia-chromosome positive) at 18 months: 87.1% (95% CI 84.1-90.0) with imatinib versus 34.7% (95% CI 29.3-40.0) with interferon plus cytarabine (P<0.001).
  • Estimated complete cytogenetic response at 18 months: 76.2% (95% CI 72.5-79.9) versus 14.5% (95% CI 10.5-18.5) (P<0.001).
  • Estimated freedom from progression to accelerated-phase or blast-crisis CML at 18 months: 96.7% versus 91.5% (P<0.001).

Harms

  • Imatinib was better tolerated than interferon alfa plus low-dose cytarabine. Specific adverse-event rates are not given in the abstract.

Clinical Use

Practice impact

  • Use a BCR-ABL tyrosine kinase inhibitor, not interferon plus cytarabine, as first-line therapy for newly diagnosed chronic-phase CML.

Applicability

  • Most applicable to newly diagnosed chronic-phase CML. The background notes high imatinib response rates after interferon failure, but this comparison is first-line.

Limitations

  • The abstract does not name a single primary end point or report overall survival.
  • Median follow-up was 19 months.
  • Crossover was allowed for failure or intolerance, which can blur longer-term arm comparisons.
  • Drug doses are not stated in the abstract.

Common misinterpretations

  • This paper does not report overall survival; the advantage is cytogenetic response, tolerability, and 18-month freedom from accelerated or blast phase.
  • Do not treat the 18-month progression difference as a long-term survival result.

Citation

O'Brien SG, Guilhot F, Larson RA, et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2003;348(11):994-1004. doi:10.1056/NEJMoa022457

In terms of hematologic and cytogenetic responses, tolerability, and the likelihood of progression to accelerated-phase or blast-crisis CML, imatinib was superior to interferon alfa plus low-dose cytarabine as first-line therapy in newly diagnosed chronic-phase CML.