What is your preferred dosing and schedule for interferon in pregnant CML patients?

The ideal starting dose for interferon in pregnant patients is a bit of a challenge because of gaps in the evidence base. In the IRIS study, interferon alfa at a dose of 5 million units/m2 was administered on a daily basis (along with cytarabine) and the toxicities of this regimen are well known but the dose of interferon was the standard of care prior to the TKI era. Many studies have shown that pegylated interferons are better tolerated, and in many instances, are more effective. The challenge is that pegylated interferons had their advent after the TKI era. A small clinical study (reviewed in Bukowski et al. Cancer 95:389, 2002) found that pegylated interferon doses above 7.5 mcg/kg weekly were not tolerated in CML patients, but that doses up to 6 mcg/kg/week did appear to be tolerable and likely provided a higher "area under the curve" than non-pegylated interferon. Flat dosing regimens of pegylated interferon in combination with imatinib have been evaluated, but the tolerated dose of interferon is much lower than the single agent dosing. Thus, the ultimate answer to the question is challenging: I would not recommend non-pegylated interferon at this time, but the evidence base in CML patients receiving pegylated interferon is thin.

My practical approach depends on the patient's current response to TKI. If the patient has MR 4.5 or better, I would suspend the TKI and follow BCR-ABL PCRs monthly. If MR3 is lost, I would initiate pegylated interferon. For patients with a starting response above MR 4.5, I would start pegylated interferon at a dose of 2mcg/kg weekly and up-titrate on a monthly basis as tolerated, recognizing that the patient will be likely be able to resume TKI on delivery.