data from the largest randomized, controlled (and only phase III) trial of
imatinib mesylate (Gleevec) confirm the drug’s superiority to interferon-alfa
and cytara-bine as first-line treatment of newly diagnosed chronic-phase
chronic myeloid leukemia (CML) but raise interesting questions about what
happens within the marrow after CML-causing Philadelphia-chromosome-positive
(Ph+) cells are beaten down to undetectable levels.
Richard Larson, MD, reported 18-month follow-up data on
behalf of the IRIS (International Randomized IFN vs STI571) Study Group in a
plenary presentation at the 44th
Annual Meeting of the American Society of Hematology (ASH abstract 2).
Dr. Larson said that imatinib (which has the additional
appeal of being an oral drug) improved complete cytogenetic responses to 76% vs
14% with interferon-alfa plus cytarabine (IFN + Ara-C) and increased 18-month
progression-free survival to 92% vs 73% with IFN + Ara-C (see
Stephen Mackinnon, MD, head of the bone marrow transplant program,
University College, London, UK, in his introduction to the presentation, said,
"Imatinib [also known as STI571] is clearly the drug of choice for newly
diagnosed CML, and a lot of hematologists think STI means ‘stop transplant immediately’."
Dr. Mackinnon pointed out that although the only cure for
CML is allogeneic bone marrow transplantation, most patients with CML are
unlikely to have allogeneic transplantation either because they are too old or
because they lack compatible marrow donors. "Imatinib is probably not a cure,
since most patients in cytogenetic complete remission remain PCR [polymerase
chain reaction]-positive, but it might be possible to produce a ‘functional
cure’ if these remissions have sufficient durability. The durability is yet
unknown," he said.
The IRIS study included 1,106 newly diagnosed CML patients
randomized either to imatinib 400 mg/d orally or IFN (target dose 5 MU/m2/d
subcutaneously) plus Ara-C (20 mg/m2/d
subcutaneously) for 10 days every month.
Patients were allowed to cross over to the alternate arm if
stringent criteria for treatment failure or intolerance were met, a feature
that greatly complicated interpretation of the data on progression-free and
overall survival. By the time of this analysis, 86% of patients randomized to
imatinib remained on that treatment, but only 11% of those randomized to IFN +
Ara-C were still taking that combination, while 58% had crossed over to