Page 81 - Haematologica3

Pegylated interferon-α in myelofibrosis
reported in the reference cohorts used to establish the prognostic scores, especially in higher risk categories: according to the Lille score (8.9 versus 7.75 years for low risk, 5.42 versus 2.17 years for intermediate rsik and 4.46 versus 1.08 years for high-risk) and to the DIPSS score (6.9 versus 4 years for intermediate-2 and 4.58 versus 1.5 years for high-risk patients).20,21 For patients with IPSS interme- diate-2 or high-risk, the 5-year actuarial survival rate was 60% from diagnosis and 48.6% from the first prescription of interferon. We did not observe any differences between patients with primary and secondary myelofibrosis with regards to median overall survival (7.4 versus 7 years, P=0.82) or leukemia-free survival (not reached for both, P=0.95). The type of driver mutation had a statistically sig- nificant impact on survival: the median overall survival was 13.5 years for CALR-mutated patients compared to 7 years for JAK2-mutated patients (P<0.0001).
Causes of death were documented in 29/32 patients (90.6%): eight had a secondary malignancy including transformation to AML in seven and secondary cancer in one, seven died of complications of myelofibrosis/cytope- nia, five transplanted patients had fatal graft-versus-host disease (GvHD), five had cardiovascular events and four died of infections.
Overall, the disease evolved to acute myeloid leukemia in eight patients (13%), only one of whom was alive at the time of the analysis. Transformation to AML occurred during pegylated interferon-α2a treatment in three
patients at a median time of 1.2 years after initiation of pegylated interferon-α2a therapy (1.3 years since the diag- nosis of myelofibrosis). In five patients, the transforma- tion to acute myeloid leukemia occurred after discontinu- ation of pegylated interferon-α2a, at a median of 4.2 years after initiation of interferon and 6.8 years since the diag- nosis of myelofibrosis (the median duration of interferon treatment in these 5 patients was 2.1 years).
Discontinuation of pegylated interferon-α2a
At the time of analysis, 16 patients (25.8% of the entire cohort, 53.3% of the living patients) were still being treat- ed with pegylated interferon-α2a. Forty-five patients (72.6%) had discontinued interferon treatment: 25 (55.6%) due to resistance and 20 (44.4%) due to intolerance. Resistance was defined by myelofibrosis progression (n=19), transformation to acute myeloid leukemia (n=3) or failure of the disease to improve (n=3). Intolerance includ- ed occurrence of new cytopenia (n=8), psychiatric compli- cations (n=6), fatigue (n=2), cutaneous porphyria (n=1), type 2 diabetes mellitus (n=1) or other (n=2). The median duration of pegylated interferon-α2a treatment was 20 months in patients with resistance compared to 12 months in those with intolerance. Patients developing intolerance to pegylated interferon-α2a had longer median overall sur- vival and leukemia-free survival than patients with resist-
ance (P=10-5 and P=0.048, respectively) (Figure 2A,B).
Of the 45 patients who stopped interferon treatment, 15
AB
CD
Figure 1. Survival of the whole study cohort. (A) Overall and (B) leukemia-free survival of the whole cohort and survivals according to the prognostic (C) Lille and (D) DIPSS scores.
haematologica | 2018; 103(3)
441