Decrease in JAK2 V617F allele burden is not a prerequisite to clinical response in patients with polycythemia vera

Abstract

Background: Although reduction in the JAK2(V617F) allele burden (%V617F) has been suggested as a criterion for defining disease response to cytoreductive therapy in polycythemia vera, its value as a response monitor is unclear. The purpose of this study is to determine whether a reduction in %V617F in polycythemia vera is a prerequisite to achieving hematologic remission in response to cytoreductive therapy.

Design and methods: We compared the clinical and hematologic responses to change in %V617F (molecular response) in 73 patients with polycythemia vera treated with either interferon (rIFNα-2b: 28, Peg-rIFNα-2a: 18) or non-interferon drugs (n=27), which included hydroxyurea (n=8), imatinib (n=12), dasatinib (n=5), busulfan (n=1), and radioactive phosphorus (n=1). Hematologic response evaluation employed Polycythemia Vera Study Group criteria, and molecular response evaluation, European Leukemia Net criteria.

Results: Of the 46 treated with interferon, 41 (89.1%) had a hematologic response, whereas only 7 (15.2%) had a partial molecular response. Of the 27 who received non-interferon treatments, 16 (59.3%) had a hematologic response, but only 2 (7.4%) had a molecular response. Median duration of follow up was 2.8 years. Statistical agreement between hematologic response and molecular response was poor in all treatment groups.

Conclusions: Generally, hematologic response was not accompanied by molecular response. Therefore, a quantitative change in %V617F is not required for clinical response in patients with polycythemia vera.

Figure 1.

Proportion of molecular response (CmolR + PMolR) in patients with hematologic response (CHR + PHR). MolR: molecular response; CmolR: complete molecular response; PmolR: partial molecular response; HR: hematologic response; CHR: complete hematologic response; PHR: partial hematologic response; rIFNα-2b: recombinant interferon alpha-2b therapy; Peg-rIFNα-2b: pegylated recombinant interferon alpha-2a therapy; Non-IFN: non-interferon therapy.

Figure 2.

Box-and-whisker plots. Boxes represent the interquartile distances. Upper and lower limits of the boxes indicate the 75th and 25th percentile, respectively. Horizontal lines in the boxes represent the median. The box and the whiskers together indicate the area in which all observations are found, unless outliers are present. When a given observation is located more than 1.5 times the interquartile distance (i.e. above the 75^th or below the 25^th percentile) then this observation is called an outlier. (A) Median JAK2^V617F Allele burden for the 1^st and final JAK2^V617F determinations in PV patients treated with Peg-rIFNα-2a who achieved a hematologic response (CHR+PHR) (n=16). Median 72.1 and 68.6% for 1^st and 2^nd JAK2V617F determinations, respectively (horizontal bars) (P=0.18 by Wilcoxon’s signed rank test). (B) Median JAK2V617F allele burden for the 1^st and final JAK2V617F determinations in PV patients treated with rIFNα-2b who achieved a hematologic response (CHR+PHR) (n=25). Median 42.3 and 52.5% for 1^st and 2^nd JAK2V617F determinations, respectively (horizontal bars) (P=0.26 by Wilcoxon’s signed rank test). (C). Median JAK2V617F allele burden for the 1^st and final JAK2V617F determinations in PV patients treated with non-interferon drugs who achieved a hematologic response (CHR+PHR) (n=16). Median=41.4 and 31.5% for 1^st and 2^nd JAK2V617F determinations, respectively (horizontal bars) (P=0.33 by Wilcoxon’s signed rank test). CHR: complete hematologic response; PHR: partial hematologic response.