Pegylated interferon alfa-2a yields high rates of hematologic and molecular response in patients with advanced essential thrombocythemia and polycythemia vera.
OBJECTIVE
We conducted a phase II study of pegylated interferon alfa-2a (PEG-IFN-alpha-2a) in patients with essential thrombocythemia (ET) and polycythemia vera (PV).


METHODS
Seventy-nine patients (40 with PV and 39 with ET) have been treated. Median time from diagnosis to PEG-IFN-alpha-2a was 54 months in patients with PV and 33 months in patients with ET. Eighty-one percent of patients had received prior therapy. The first three patients received PEG-IFN-alpha-2a at 450 microg weekly. As a result of poor tolerance, this dose was decreased in a stepwise manner to a current starting dose of 90 microg weekly. Seventy-seven patients are evaluable and have been observed for a median of 21 months.


RESULTS
The overall hematologic response rate was 80% in PV and 81% in ET (complete in 70% and 76% of patients, respectively). The JAK2(V617F) mutation was detected in 18 patients with ET and 38 patients with PV; sequential measurements by a pyrosequencing assay were available in 16 patients with ET and 35 patients with PV. The molecular response rate was 38% in ET and 54% in PV, being complete (undetectable JAK2(V617F)) in 6% and 14%, respectively. The JAK2(V617F) mutant allele burden continued to decrease with no clear evidence for a plateau. The tolerability of PEG-IFN-alpha-2a at 90 microg weekly was excellent.


CONCLUSIONS
PEG-IFN-alpha-2a resulted in remarkable clinical activity, high rates of molecular response, and acceptable toxicity in patients with advanced ET or PV. The ability of PEG-IFN-alpha-2a to induce complete molecular responses suggests selective targeting of the malignant clone.
Quintás-Cardama
Alfonso
A
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Kantarjian
Hagop
H
Manshouri
Taghi
T
Luthra
Rajyalakshmi
R
Estrov
Zeev
Z
Pierce
Sherry
S
Richie
Mary Ann
MA
Borthakur
Gautam
G
Konopleva
Marina
M
Cortes
Jorge
J
Verstovsek
Srdan
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D053614:Janus Kinase 2 / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D009503:Neutropenia / Q000139:chemically induced; D011087:Polycythemia Vera / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use*; D011994:Recombinant Proteins; D013920:Thrombocythemia, Essential / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D016896:Treatment Outcome; D055815:Young Adult
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C507924:JAK2 protein, human; D053614:Janus Kinase 2; C100416:peginterferon alfa-2a