Efficacy and Safety of Peg-Interferon-α2a In Myelofibrosis: a Study of the FIM and GEM French Cooperative Groups
Authors: Ianotto Jean-Christophe , Boyer-Perrard Françoise , Demory Jean-Loup , Rey Jerome , Roy Lydia , Berthou Christian , Dupriez Brigitte , Ranta Dana , Potard Mireille , Schoenwald Michele , Abgrall Jean-François , Kiladjian Jean-Jacques 
Published: October 2019

Abstract
Abstract 4103

Background:
The moderate effect of most palliative treatments in primary and secondary myelofibrosis (MF), in addition to the limited possibilities of allogeneic stem cell transplantation, has incited physicians to look for alternative treatments. Since 1987, several studies have suggested that interferon may be beneficial in the treatment of MF. However, important hematological and general limiting toxicities frequently occur in MF patients (pts), leading to rapid treatment discontinuation in more than 50% of pts. Better results were recently reported in a small series of 13 MF pts treated with Peg-Interferon-α2a (Ianotto et al., Br J Haematol, 2009). The present study aimed to collect data of pts with primary and secondary MF treated with Peg-Interferon-α2a in French centers members of the FIM (French Intergroup of Myeloproliferative disorders) and GEM (Groupe d'Etudes des Myelofibroses) groups, to better assess tolerance and efficacy of this form of interferon in MF.

Patients and Methods:
Between Dec 2006 and Feb 2010, 39 MF pts treated with Peg-Interferon-α2a were registered from 10 different French centers affiliated to FIM and GEM groups. Age of pts ranged from 41 to 81 years, 21 were men and 18 women. Sixteen pts had primary MF, 13 had post-PV and 10 post-ET MF, respectively. Twenty-five patients (64%) were JAK2V617F positive. Twenty-eight patients had previously received other cytoreductive treatment. Clinical and biological parameters were collected at diagnosis and every 3 months. Responses were assessed according to the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) criteria. Analyses were performed in July 2010, after a median follow-up of 18 months (range: 3 – 42 months).

Results:
Among the 28 patients with splenomegaly, we observed 10 responses (36%) including 7 complete and 3 partial responses. Fourteen patients had constitutional symptoms which resolved in 8 of them (57%). Seven of 15 patients (47%) with an initial hemoglobin level below 100 g/L achieved complete response (CR). Three of 8 (37%) transfused pts became transfusion-independent. Twenty-two patients had abnormal WBC count which normalized in 13 of them (59%). Platelet count was abnormal in 27 patients, and 14 (52%) achieved CR with Peg-Interferon-α2a treatment. The evolution of the JAK2V617F allele burden is currently under investigation and will be presented at the meeting. The initial median dose of Peg-Interferon-α2a effectively received was 103 μ g/wk, further decreased to a median of 85 μ g/wk after one year. At time of analysis, treatment was stopped in 11/39 (28%) pts due to side effects, inefficacy or hematologic evolution.

Conclusion:
In this observational study, we found higher efficacy and better tolerance of interferon than previously reported in patients with primary or secondary MF. Such results were possibly due to a better tolerance of the pegylated form used, and to the low-dose schedule applied by the physicians. Our results suggest at least that Peg-Interferon-α2a should be considered as a possible therapeutic option in selected MF patients. Future clinical trials in MF will hopefully involve combinations of low dose Peg-Interferon-α2a with JAK2-inhibitors or immunomodulatory agents in order to improve tolerability and increase efficacy.

Disclosures:
Off Label Use: This is an observational study of the off-label use of peg-Interferon-alfa2a in myelofibrosis.