December 12, 2023
John Schieszer
The final analysis of the DALIAH trial (ClinicalTrials.gov Identifier: NCT01387763), which was presented at the ASH Annual Meeting 2023, showed no significant differences with hydroxyurea (HU) and pegylated interferon-alpha2 (IFNα) in patients with myeloproliferative neoplasms (MPNs) receiving long-term treatment.
This modified intention-to-treat (ITT) analysis detected no significant difference in the molecular response (MR) or clinical hematologic response (CHR) rates between HU and IFNα with long-term treatment among patients with MPNs.
However, a higher treatment discontinuation rate in the IFNα group (65%) was noted, and when using the per-protocol principle the MR or CHR rates were superior in the IFNα group at 36 months and beyond. The study authors also noted that increasing evidence on the efficacy and safety of IFNα is emerging.
The DAHLIA study was a randomized phase III trial of HU versus IFNα in newly diagnosed or untreated patients with MPN. The cohort included a total of 203 patients with essential thrombocythemia (ET), polycythemia vera (PV), prefibrotic myelofibrosis (PreMF), and primary myelofibrosis (PMF).
All participants older than 60 years were randomly assigned (1:1:1) to HU, IFNα-2a, or IFNα-2b. Participants who were 60 years or younger were randomly assigned to receive IFNα-2a or IFNα-2b. The primary outcome was the JAK2V617F MR rate at 18 months, at 36 months, and at 60 months per 2009 European LeukemiaNetwork (ELN; ET, PV, PreMF) or 2005 European Myelofibrosis Network (EUMNET; PMF) criteria.
The 203 patients in the modified ITT cohort were made up of ET, 73 (36%); PV, 89 (44%); PreMF, 16 (8%); and PMF, 25 (12%). The baseline characteristics were well balanced in the different groups. However, the median age varied (HU, 68 years vs IFNα, 59 years; P <.0001).
The MR rate by ITT analysis was similar between HU and IFNα at 18 months (19% vs 21%), at 36 months (19% vs 26%) and at 60 months (23% vs 24%). However, the JAK2V617F allele burden was significantly lower in the IFNα group at month 36 and beyond.
The CHR rate by ITT analysis was higher with HU at 18 months (58% vs 38%, P =.03) but similar at all other time points. Comparable efficacy results were found in a post hoc subgroup analysis comparing HU with IFNα in patients older than 60 years. However, the MR and CHR rates were superior in the IFNα group compared to the HU group at 36 months and beyond among patients remaining on treatment.
The MR rates by per-protocol analysis were 23% HU versus 56% IFNα at 36 months, 27% HU versus 59% INFa at 48 months and 35% HU versus 67% INFα at 60 months. The CHR rates were significantly different at 36 months (33% HU versus 67% INFα) and at 60 months (38% HU versus 62% INFα).
Overall treatment discontinuation at 60 months was 60% (HU, 37%; IFNα, 65%; P =.0019). The most common cause of treatment discontinuation was adverse events (AEs; HU, 16%; IFNα, 43%). More AEs ≥ grade 3 occurred in HU (58%) vs IFNα (45%). In 16 patients, 19 major thrombotic events were reported (4 events in 4 patients with HU; 12 events in 10 patients with IFNα in patients older than 60 years; 3 events in 2 patients with IFNα in patients 60 years or younger).
No participants had their disease morph into secondary acute myeloid leukemia; however, 5 patients died during follow-up (HU, 2; IFNα, 3).
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of disclosures.
Reference
Knudsen TA, Lund Hansen D, Frans Ocias L, et al. Final analysis of the Daliah trial: a randomized phase III trial of interferon-α versus hydroxyurea in patients with MPN. Abstract 746.