A meta-analysis of selected studies of patients with essential thrombocythemia (ET) and/or polycythemia vera (PV) treated with various formulations of interferon alpha provided support for the use of these agents in the long-term treatment of patients with these conditions. These findings were published in Leukemia.
ET, PV, and myelofibrosis comprise the BCR/ABL1-negative myeloproliferative neoplasms (MPNs). ET is principally characterized by a high platelet count, and a high red blood cell count is a defining characteristic of PV. Hence, patients with these conditions may be at increased risk of experiencing a thromboembolic event.
Cytoreductive treatment approaches, such as hydroxyurea, anagrelide, and interferon alpha, are used in the first-line setting to lower the risk of thrombosis and alleviate the symptom burden, including fatigue and splenomegaly, that may be associated with ET and PV in patients with these conditions considered to be at increased risk of vascular complications. Nevertheless, questions remain regarding the role of interferon alpha in these settings.
Following a systematic review of the medical literature, a meta-analysis of data from selected studies investigating the safety and effectiveness of interferon alpha and pegylated interferon alpha in the upfront treatment setting for patients with ET and PV was conducted.
The primary outcome measure of the study was objective response rate (ORR), defined as a composite of the rates of complete response (CR), partial response (PR), complete hematologic response (CHR), and partial hematologic response (PHR). Although some of the definitions of these parameters, particularly CHR and PHR, varied according to the primary publication, they were mainly based on “the normalization/improvement of peripheral blood counts and resolution of MPN-associated symptoms.”
Of 8587 unique publications identified, 143 underwent a full review, and 44 studies were included in this meta-analysis. These included 30 and 23 studies of ET and PV, respectively, involving a total of 730 patients with ET and 629 patients with PV. Various interferon alpha formulations and treatment schedules were used with nonpegulated interferon alpha (31 studies), pegylated interferon alpha (12 studies), and ropegylated interferon alpha (1 study).
The overall ORR for patients with ET and PV was 80.6% and 76.7%, respectively, demonstrating the effectiveness of interferon-alpha and pegylated interferon alpha in these settings.
Of note, the annualized rate of thrombotic events was found to be low for patients with PV (0.5%) and ET (1.2%), with no significant differences observed for those treated with interferon alpha vs pegylated interferon alpha.
In addition, evaluations of ORR during treatment periods represented by less than 24 months and 24 months or longer were not significantly different for patients with ET or PV, demonstrating the long-term effectiveness of interferon alpha-based therapy for patients with these conditions.
An assessment of the impact of patient age on ORR revealed similar findings for those with ET treated with interferon-alpha-based therapy in the group of studies where median patient age was younger than 60 years (79.7%) and 60 years or older (78.5%; P =.70). However, in the setting of PV, the ORR for the group of studies with a median patient age of younger than 60 years (79.0%) was significantly higher compared with the ORR observed in the group of studies where the median patient age was 60 years or older (41.8%; P <.001).
Nevertheless, the study authors noted that “extrapolating these results to the individual patient level is limited as we only compared studies stratiﬁed by median patient age and cross-study heterogeneity remains a potential confounder.”
Although inconsistencies were observed across studies regarding reports of adverse events (AEs), with the absence of a standardized grading system in older studies, descriptive summaries of AEs showed flu-like symptoms, malaise, and fever were common in patients treated with these agents, with lower rates of neurological, hepatic, and psychiatric AEs also observed.
The annual treatment discontinuation rate for patients treated with these agents was 8.8% and 6.5% in the settings of ET and PV, respectively
“While most adverse events were reportedly manageable with antipyretics and dose adjustments, the frequency of dosing (up to daily for older formulations) can make even low-grade adverse events difﬁcult to tolerate for patients and lead to treatment discontinuation,” noted the investigators.
“Adverse events remain a major limitation to treatment with [interferon], but the high ORR and the durable molecular remission seen in a subset of patients suggest [interferon-alpha-based therapy] to be a reasonable therapeutic option for patients with ET or PV,” they stated in their conclusion.
Disclosures: Multiple authors declared affiliation with industry. Please refer to the original article for a full list of disclosures.
Bewersdorf JP, Giri S, Wang R, et al. Interferon alpha therapy in essential thrombocythemia and polycythemia vera — a systematic review and meta-analysis. Leukemia. Published online September 1, 2020. doi:10.1038/s41375-020-01020-4