DALIAH: Peginterferon-α head-to-head against hydroxyurea in MPN

Molecular response (MR) rates and complete haematologic response (CHR) rates did not differ between peginterferon-α (IFNα) or hydroxyurea-treated participants with myeloproliferative neoplasms (MPN), results of the phase 3 DALIAH trial showed.

Although hydroxyurea is the most common first-line cytoreductive therapy in patients with high-risk MPN, this agent has been associated with possible leukaemogenic potential [1]. Dr Trine Knudsen (University Hospital Odense, Denmark) introduced her talk: “On the other hand, off-label experience with IFNα-2a showed high response rates and a disease-modifying potential of this agent in MPN [2].”

The phase 3 DALIAH trial (NCT01387763) compared MR rates of participants with newly diagnosed MPN who were treated with low-dose IFNα or hydroxyurea. Participants (aged ≤60 years; n=91) were randomised 1:1 to IFNα-2a or IFNα-2b, whereas participants >60 years of age (n=112) were randomised 1:1:1 to IFNα-2a, IFNα-2b, or hydroxyurea [3]. The primary outcome was the JAK2^V617F MR rate at 18, 36, and 60 months per 2009 European LeukemiaNetwork criteria (ET, PV, PreMF) or 2005 European Myelofibrosis Network (PMF) criteria. Secondary outcomes included the CHR rate at 12 months. The JAK2^V617F allele burden was measured using quantitative PCR on peripheral blood (assay sensitivity: 0.1%).

203 participants (ET: 73 [36%], PV: 89 [44%], PreMF: 16 [8%], and PMF: 25 [12%]) were included in the modified intention-to-treat (ITT) population which did not reveal significant differences in MR and CHR rates between participants treated with IFNα or hydroxyurea at any timepoint (MR at 18 months: 19% vs 21%; 36 months: 19% vs 26%; 60 months 23% vs 24%; IFNα vs hydroxyurea). The CHR rate by ITT analysis was higher with hydroxyurea at 18 months (58% vs 38%; P=0.03) but similar at all other time points (12 months: 50% vs 36%; P=0.21; 60 months: 24% vs 22%; P=0.83). “Among participants remaining on treatment (per-protocol analysis), the MR and CHR rates were superior in the IFNα group compared with the hydroxyurea group at 36 months and beyond,” noted Dr Knudsen. The MR and CHR rates (IFNα vs hydroxyurea) by per-protocol analysis were: MR at 36 months: 56% vs 23%; P=0.01; 48 months: 59% vs 27%; P=0.02; 60 months: 67% vs 35%; P=0.03; CHR at 36 months: 67% vs 33%; P=0.002; 60 months: 62% vs 38%; P=0.05.

Furthermore, the JAK2^V617F allele burden was higher in participants treated with hydroxyurea than those treated with IFNα from 36 months and beyond.  “We observed a slow but steady decline in this burden in participants receiving IFNα and more fickle results in participants treated with hydroxyurea,” stated Dr Knudsen. For histopathologic response at month 60, there was a benefit for participants on hydroxyurea (18% vs 5%; P=0.01). Also, the grade of fibrosis was more often worsened in the IFNα group at 60 months (44% vs 9%; P=0.003). Discontinuation rates were higher among IFNα users (65% vs 37%; log-rank P=0.002) and within this group. The discontinuation rates were higher with IFNα-2b than with IFNα-2a (75% vs 55%; log-rank P=0.008).

Adverse events (AEs) ≥grade 3 were seen in 58% and 45% of participants on hydroxyurea and IFNα, respectively. There were no obvious differences between specific AEs between the study groups. 19 major thrombotic events were reported in 16 participants (hydroxyurea: 4 events in 4 participants; IFNα >60 years of age: 12 events in 10 participants; IFNα ≤60 years of age: 3 events in 2 participants). None of the participants transformed into secondary acute myeloid leukaemia. “Even psychiatric disorders, a well-known side effect of interferon therapy, did not occur significantly more frequently in participants treated with IFNα,” added Dr Knudsen.

Thus, there were no differences in MR rates between hydroxyurea users and IFNα users at 60 months. However, the per-protocol analysis suggests that participants with good IFNα tolerability outperform those on hydroxyurea in the long term.

1. Kiladjian J-J, et al. J Clin Oncol. 2011;29(29):3907-3913.
2. Kiladjian J-J, et al. Blood. 2006;108(6):2037-2040.
3. Knudsen TA, et al. Final analysis of the Daliah Trial: a randomized phase III trial of Interferon-a versus hydroxyurea in patients with MPN. Abstract 746, 65^th ASH Annual Meeting, 9–12 December 2023, San Diego, CA, USA.

 

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Posted on 7 February, 202415 February, 2024