Abstract
Abstract 5055
Objective:
To retrospectively assess hematological response rates, and other clinical and molecular variables, in MPN patients treated with pegylated interferon α-2a (Pegasys®, Roche Ltd). Responses were graded according to criteria published by the European Leukemia Net for PV and ET (Barosi G et al Blood 2009;113:4829), with the exception that mesurement of spleen size using ultrasound was not routinely performed, and the European Myelofibrosis Network for PMF (Barosi G et al Blood 2005;106:2849), respectively.
Patient characteristics:
The 23 patient cohort consisted of 13 PV, 5 ET, 3 PMF and 2 post-ET/PV MF pts. Thirteen pts were JAK2V617F+, 6 were JAK2V617F wt, and in 4 pts JAK2 status is unknown. Median age was 50 years (range 26–69), 13 were female and 10 male. Median time from MPN diagnosis to start of pegylated interferon α-2a (Peg-IFN) therapy was 67 months (range 0–204). Six pts had a previous thrombotic event (TIA=2, portal vein thrombosis=2, DVT lower extremity=2), and 2 pts had a previous major hemorrhage (gynecological=1, gastrointestinal=1). Eleven pts had previously received therapy with anagrelide (n=8), hydroxyurea (n=4), interferon α-2b (n=1), busulfan (n=1) or P32 (n=1), while 12 pts had not received bone marrow suppressive therapy. All PV and ET pts were on aspirin. Phlebotomies were performed in PV with the aim of keeping the hematocrit < 0.45. Peg-IFN was given at a dose of 90 μg/week in 16 pts, 135μg/week in 6, and 180μg/week in 1.
Results:
The overall hematological response rate (CR+PR) was 18/21 (86 %), 14 pts achieving CR and 4 PR. Two pts are too early to evaluate at the time of astract submission. One PV and 1 PMF patient were non-responders. Resonse rates were similar in PV vs ET, female vs male pts, and previously treated vs previously untreated pts. Median time of follow-up on Peg-IFN therapy is 16 months (3+ - 49+). Thirteen pts are still on therapy, 9 in CR, 2 in PR, and 2 too early to evaluate. These 13 pts have very limited or no side effects. Therapy has also been stopped according to plan after long hematological CR with molecular response in 2 pts. Therapy has been discontinued in 8 pts, in five (22 %) due to side effects (depression n=3, joint pain n=3, hair loss n=2, pruritus n=1), non-response in 2 pts, and PMF progression in 1. Serial JAK2V617F measurements are available at time of abstract submission in 4 pts, 1 achieved molecular CR, 2 PR whereas 1 patient treated for 5 months had no molecular response. Three of 4 mildly anemic MF pts normalized their hemoglobin (HgB 113 → 137, 106 → 123, and 110 → 125 respectively). In one PMF patent a clear reduction of marrow fibrosis was noted, whereas it progressed in another. No thromboembolic or bleeding complications were observed during PEG-IFN therapy. Longer follow-up, as well as additional molecular and morphological studies will be presented.
Conclusions:
Pegylated interferon α-2a induced a higher hematological response rate with improved tolerability, compared to our previous experience with Peg-IFN α-2b (Samuelsson et al Cancer 2006;106:2397), although the current number of patients is limited. However, the two previous publications that describes Peg-IFN α-2a therapy in larger MPN patients cohorts have observed results similar to ours (Kiladjian JJ et al Blood. 2008;112:3065, Quintás-Cardama A et al J Clin Oncol. 2009;27:5418). Molecular responses noted in a subset of patients further highlights the effect of Peg-IFN α-2a on the malignant clone in MPN:s. Peg-IFN α-2a is a valuable therapeutic alternative in patients who tolerate initial side effects, and will soon be compared to hydroxyurea in a randomized trial in high-risk PV and ET pts performed by the MPD research consortium.
Disclosures:
Samuelsson: Roche Sweden: Advisory board on use of recombinant erytropoetin. Off Label Use: Alpha-interferon does not have a label for use in myeloproliferative neoplasms. Merup:Roche Sweden: Received honoraria for lectures on rituximab use in lymphoma.
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