PegIFN Improves Responses to Dasatinib in Newly Diagnosed CML Patients

The addition of pegylated interferon-ɑ2b (PegIFN) to the tyrosine kinase inhibitor (TKI) dasatinib yielded promising results in a small trial of newly diagnosed chronic myeloid leukemia (CML) patients.

“IFN is a good candidate to further increase the efficacy of TKI treatment, as its mode of action, induction of antitumoral immunity, and effects on stem cell proliferation and renewal, differs from TKIs,” wrote study authors led by Henrik Hjorth-Hansen, MD, PhD, of the Norwegian University of Science and Technology in Trondheim, Norway.

The study included 40 newly diagnosed CML patients. All began by receiving dasatinib for 3 months, followed by the addition of PegIFN at that point. Dosing of PegIFN began at 15 μg/week and increased to 25 μg/week over the first 3 months. The results of the trial were published in Leukemia.

At the 3-month mark prior to initiation of PegIFN, 10% of patients achieved a major molecular response (MMR) and 66% achieved a complete cytogenetic remission (CCgR). These response rates rose markedly after the introduction of PegIFN: at month 6, 82% of patients had achieved CCgR, and at month 12 this rose to 97%. Also, 55% of patients achieved an MMR at month 6, an absolute increase of 45% over month 3. The authors noted that the MMR rate at month 12 (84%) was significantly higher than seen in other studies of dasatinib alone.

The safety profile of the combination was manageable and no unexpected toxicities were observed. In total, six patients had seven serious adverse events that required hospitalization; these included bradycardia/atrial fibrillation, headache, fever, and others. Only one patient suffered a pleural effusion during the first year of treatment, though three more did during the second year of therapy.

The majority of patients (84%) remained on the combination therapy at month 12. During the first year, the entire cohort received 91.2% of the scheduled dasatinib dose and 73.4% of the scheduled PegIFN dose.

“Although follow-up time is short, our results suggest that combining dasatinib with PegIFN may increase the chance of achieving long-standing treatment-free remission,” the authors concluded. They added that these data support the development of a randomized trial of dasatinib with and without PegIFN.