Abstract 1908Poster Board I-931Previous studies of patients (pts) with polycythemia vera (PV) treated with pegylated interferon (peg-IFNá-2a) have shown an 83% complete hematologic response associated with an 89% molecular response over a median of 11 months (Kiladjian et al. Blood. 2008. 112(8):3065-3072) implying a causative relationship between molecular and hematologic responses. Our data show pts treated with rIFNá-2b or non-rIFNá-2b agents achieve hematologic response despite the absence of a molecular response suggesting that a molecular change is not a prerequisite to hematologic response.Thirty pts diagnosed with PV by the criteria of the Polycythemia Vera Study Group (PVSG) were followed clinically and hematologically with serial quantified JAK2V617F allele burden determined at six-month intervals over a mean of 21.6 months (mos) (range: 6.0 – 56.4 mos). These pts were treated with rIFNá-2b ranging from 0.5 mu to 3.0 mu three times per week depending upon clinical response. Primary clinical endpoints were hematocrit (hct) ≤45% men, ≤42% women, and no need for phlebotomy (PHL). Molecular and hematologic responses were graded according to the criteria of Barosi et al. (Blood. 2009. 113(20):4829-4833): complete hematologic response (CHR: hct ≤45% without PHL, platelets '400×109/L, WBC ≤10×109/L, normal spleen size, asymptomatic); partial hematologic response (PHR: hct ≤45% without PHL or response in 3 or more of the CHR categories); no hematologic response (NHR: failure to meet the criteria of CHR or PHR); complete molecular response (CMR: reduction of JAK2V617F marker to undetectable levels); partial molecular response (PMR: ≥50% reduction in pts with '50% mutant allele burden at baseline, or ≥25% reduction in pts with >50% mutant allele burden at baseline; applicable only to pts with ≥10% baseline allele burden); and no molecular response (NMR: failure to meet the criteria of CMR or PMR).Of the 30 pts treated with rIFNá-2b, 14 had a CHR, 13 had a PHR and 3 had NHR. Of 14 pts who had a CHR, 4 had a PMR and 10 had NMR. Of thirteen pts who had a PHR, 1 had a PMR and 12 had NMR. All 3 pts who had NHR also had NMR. Based on these data, the statistical agreement between hematologic response and molecular response was poor (kappa coefficient = 0.06, P=0.17).We then examined the hematologic responses (HR: CHR+PHR) of 25 non-rIFNá-2b treated pts, which included PHL ± anagrelide (3 pts: 2 HR/NMR, 1 NHR/NMR), dasatinib (5 pts: 5 HR/NMR), imatinib (9 pts: 3 HR/PMR, 4 HR/NMR, 2 NHR/NMR), and hydroxyurea (8 pts: 1 CHR/PMR, 7 HR/NMR). The minimal molecular response to dasatinib and hydroxyurea is noteworthy. Likewise, there was poor statistical agreement between hematologic response and molecular response for non-rIFNá-2b treated patients (kappa coefficient = 0.05, P=0.21).Of all 55 pts (rIFNá-2b and non-rIFNá-2b), those 9 patients with a PMR had a hematologic response (7 CHR and 2 PHR). Of 46 NMR's, 40 pts (87%) had a hematologic response (16 CHR, 24 PHR). Thus, NMR did not exclude the possibility of achieving CHR. Regardless of therapy, we demonstrate poor agreement between hematologic and molecular responses for these drugs (all pts: kappa = 0.05, P=0.13). This suggests a difference in action between peg-IFNá-2a, shown to cause molecular and hematologic responses concurrently, and several drugs we examined leading to clinical response without necessarily changing JAK2V617F allele burden. In this regard, other parameters such as bone marrow morphology and new biological markers may be useful in reconciling the differences.In summary, we find that a hematologic response is not always accompanied by a molecular response in PV pts treated with either rIFNá-2b or some non-rIFNá-2b drugs. We thus conclude that a reduction in JAK2V617F allele burden is not always required for patients to achieve hematologic response, and that following the JAK2V617F biomarker may be drug-dependent and may not always be a reliable measure of response. This warrants the importance of the randomized trial planned to compare peg-IFNá-2a to the current standard of treatment, hydroxyurea. Disclosures:No relevant conflicts of interest to declare.