Pegylated interferon-alfa-2a induces complete hematologic and molecular responses with low toxicity in polycythemia vera.
Interferon-alpha (IFN-alpha) is a nonleukemogenic treatment of polycythemia vera (PV) able to induce cytogenetic remissions. Its use is limited by toxicity, leading to treatment discontinuation in approximately 20% of patients. We completed a phase 2 multicenter study of pegylated IFN-alpha-2a in 40 PV patients. Objectives included evaluation of efficacy, safety, and monitoring of residual disease using JAK2V617F quantification (%V617F). Median follow-up was 31.4 months. At 12 months, all 37 evaluable patients had hematologic response, including 94.6% complete responses (CRs). Only 3 patients (8%) had stopped treatment. After the first year, 35 patients remained in hematologic CR, including 5 who had stopped pegylated IFN-alpha-2a. Sequential samples for %V617F monitoring, available in 29 patients, showed %V617F decrease in 26 (89.6%). Median %V617F decreased from 45% before pegylated IFN-alpha-2a to 22.5%, 17.5%, 5%, and 3% after 12, 18, 24, and 36 months, respectively. Molecular CR (JAK2V617F undetectable) was achieved in 7 patients, lasting from 6(+) to 18(+) months, and persisted after pegylated IFN-alpha-2a discontinuation in 5. No vascular event was recorded. These results show that pegylated IFN-alpha-2a yields high rates of hematologic and molecular response in PV with limited toxicity, and could even eliminate the JAK2 mutated clone in selected cases. Available at www.clinicaltrials.gov as #NCT00241241.
Kiladjian
Jean-Jacques
JJ
Assistance Publique-Hôpitaux de Paris, Hôpital Avicenne, Service d'Hématologie Clinique and Paris 13 University, Bobigny, France.
Cassinat
Bruno
B
Chevret
Sylvie
S
Turlure
Pascal
P
Cambier
Nathalie
N
Roussel
Murielle
M
Bellucci
Sylvia
S
Grandchamp
Bernard
B
Chomienne
Christine
C
Fenaux
Pierre
P
D000328:Adult; D004337:Drug Carriers / Q000627:therapeutic use; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D053614:Janus Kinase 2 / Q000235:genetics; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011087:Polycythemia Vera / Q000097:blood* / Q000628:therapy*; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins; D012074:Remission Induction; D013997:Time Factors; D016896:Treatment Outcome
D004337:Drug Carriers; 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