PEG‐IFN‐α‐2b therapy in BCR‐ABL–negative myeloproliferative disorders

Abstract

BACKGROUND.Interferon‐alpha (IFN‐α) has shown significant activity in the treatment of BCR‐ABL–negative myeloproliferative disorders (MPDs), particularly essential thrombocythemia (ET) and polycythemia vera (PV). PEG‐IFN‐α‐2b is a pegylated IFN‐α‐2b with a significant advantage over nonpegylated form in that it is administered once a week.METHODS.Thirty‐eight patients with BCR‐ABL–negative MPDs were treated with PEG‐IFN‐α‐2b, given subcutaneously weekly, at the starting dose of 3 μg/kg/wk for the first 14 patients and then 2 μg/kg/wk for the next 24 patients, with intent to treat patients as long as they benefited from the therapy.RESULTS.Median age was 54 years. Patient diagnoses were: 13 (34%) ET; 11 (29%) primary myelofibrosis (PMF); 5 (13%) BCR‐ABL–negative chronic myeloid leukemia (CML); 4 (10.5%) hypereosinophilic syndrome (HES); 4 (10.5%) PV; and 1 (3%) unclassified myeloproliferative disease (uMPD). Recorded grade 3–4 toxicities were related to fatigue, myelosuppression, and musculoskeletal pain. Ten (26%) patients stopped treatment because of toxicity. Thirteen (34%) patients achieved a complete remission, and 4 (11%) achieved a partial response. Only 1 patient with PMF responded. Median time to response was 5 months. Median duration of response was 20 months. Three patients had a sustained response for >24 months.CONCLUSIONS.PEG‐IFN‐α‐2b, with proper dose modifications, is effective in controlling disease in a significant proportion of BCR‐ABL–negative MPD patients, particularly ET and PV. However, toxicities encountered with PEG‐IFN‐α‐2b therapy are similar to those obtained with conventional IFN‐α, thus limiting the duration of therapy. Cancer 2007. © 2007 American Cancer Society.

Guideline for the diagnosis and management of myelofibrosis

“…Both standard and pegylated preparations of interferon-alpha appear to have little clinical effect in reducing splenomegaly and, as a result, their use is not recommended (Tefferi et al, 2001a;Jabbour et al, 2007;Ianotto et al, 2009). They do, however, have a role as myelosuppressive agents (see 'Myelosuppression Therapy' section).…”

“…In view of the particularly high rates of toxicity in PMF, the use of IFN in MPNs has been mainly restricted to PV and ET. Nevertheless, a number of studies of IFN in MF have been reported, although they give highly heterogeneous results, a fact complicated by non-standardized reporting of responses and lack of randomized control trial data (Gilbert, 1998;Tefferi et al, 2001a;Radin et al, 2003;Jabbour et al, 2007;Ianotto et al, 2009;Silver & Vandris, 2009). More recently, two small, retrospective, observational studies have shown more promising results in PMF patients.…”

Interferon-α in acute myeloid leukemia: an old drug revisited

“…9 Recent studies have underscored the therapeutic value of pegylated IFN-a in CML 81 and other myeloproliferative neoplasms (polycythemia vera, essential thrombocythemia and primary myelofibrosis). [81][82][83][84][85][86] Preliminary data are available on its clinical use in AML; a recent case study by our group has illustrated the therapeutic potential of pegylated IFN-a in the setting of AML. 15 This was demonstrated by the induction of a long-lasting complete remission in a poor-prognosis AML superimposed on a preceding state of primary myelofibrosis.…”

PEG‐IFN‐α‐2a therapy in patients with myelofibrosis

“…More recent reports have indicated that IFN-a is most frequently used in myelofibrotic patients (Kiladjian et al, 2008a). However, the use of Peg-IFN (a-2b) was reported only once and was found to produce poor results, with only one patient out of 11 achieving a 'complete response' (Jabbour et al, 2007). In a recent report, Peg-IFN a-2a induced haematological and even molecular responses in polycythaemic patients (Kiladjian et al, 2008b).…”