More patients with chronic myeloid leukemia (CML) in chronic phase achieve molecular response when peginterferon alfa-2a is added to imatinib therapy, but toxic side effects make completing treatment difficult for many, according to analysis of SPIRIT trial data (N Engl J Med. 2010;363:2511-2521). The researchers concluded that this increase in molecular responses could translate into better survival.
The SPIRIT Investigators and the France Itnergroupe des Leucémies Myéloïdes Chroniques randomized 636 patients with untreated chronic-phase CML to imatinib alone (400 mg/day; standard of care at the time of trial design), imatinib plus cytarabine (20 mg/m2, days 15-28), imatinib plus peginterferon alfa-2a (90 μg weekly), or to high-dose imatinib alone (600 mg/day). Molecular response was defined as a decrease in the ratio of transcripts of the tyrosine kinase BCR-ABL of at least 3 log10 units.
At 12 months follow-up, the rate of molecular response was higher in the imatinib plus peginterferon alfa-2a group than in the 400-mg imatinib alone group (30% vs 14%; P = .001). The response rate was significantly higher in those treated for 12 months than for those treated less than 12 months (49% vs 23%).
Only 46% of patients completed 12 months of treatment with imatinib plus peginterferon alfa-2a, primarily because grade 3 and 4 adverse events were more frequent with this combination. These included rash, depression, asthenia, and edema.
Because they observed a positive relationship between duration of the therapy and the rate of molecular responses and because there was a high rate of treatment discontinuation from adverse effects, researchers lowered the dose of peginterferon alfa-2a. They postulated that “a lower dose of peginterferon alfa-2a (eg, 45 μg per week) might allow the combination to be given for a longer period and preserve its apparent increased antitumor efficacy.”