Phase III DALIAH trial: Peg-IFNα in newly diagnosed MPN

Results from the randomized, open-label, phase III DALIAH trial (NCT01387763), evaluating pegylated interferon alpha-2 (peg-IFNα) vs hydroxyurea (HU) in 203 adults with newly diagnosed (ND) myeloproliferative neoplasms (MPN), were published in eClinicalMedicine by Knudsen et al. The primary endpoint was JAK2 V617F molecular response (MR) at 18, 36, and 60 months.

Key data: In the modified intention-to-treat (mITT) analysis (HU, n = 38; peg-IFNα, n = 165), JAK2 V617F MR rates were similar between the HU and peg-IFNα groups at 18 months (19% vs 21%; p = 1.00), 36 months (19% vs 26%; p = 0.64), and 60 months (23% vs 24%; p = 1.00). In the per-protocol (PP) analysis, restricted to patients remaining on therapy, peg-IFNα vs HU demonstrated a superior MR at 36 months (56% vs 23%; p = 0.01) and 60 months (67% vs 35%; p = 0.03). From Month 36 onwards, median JAK2 V617F variant allele frequency (VAF) was lower with peg-IFNα vs HU (p < 0.05). There were no significant differences between peg-IFNα vs HU in 12-month complete hematologic response (CHR) rate (p = 0.27) or bone marrow response (BMR) at 36 months (ITT, p = 0.49; PP, p = 1.00). At 60 months BMR was significantly higher with peg-IFNα vs HU in the ITT analysis (p = 0.01), but not in the PP analysis (p = 0.12). At 60 months, treatment discontinuation was significantly more frequent with peg-IFNα vs HU (65% vs 37%, p = 0.0019). Grade ≥3 adverse events (AEs) were reported in 45% of patients receiving peg-IFNα vs 58% of patients receiving HU (p = 0.21).

Key learning: In the DALIAH trial, peg-IFNα and HU demonstrated similar MR rates in the ITT population, though peg-IFNα achieved superior long-term MRs among patients who remained on therapy through Month 60. These findings highlight the potential for long-term disease control with peg-IFNα in select patients with ND MPN.