ALBERT

Description: Abstract 1747 Background. IFN-alpha (IFN) is reported to induce molecular response in patients with chronic myeloproliferative neoplasms and may therefore improve survival. However, the use of conventional and pegylated IFNs is limited by toxicity, leading to treatment withdrawals in a substantial proportion of patients. In polycythemia vera (PV), recently published phase II data indicate occurence of grade 3 and 4 toxicities in 20%, and toxicity-related discontinuations in 22–24% of patients administered once weekly with pegylated IFNs. Results from large-scale randomized studies of IFNs in PV are not available. AOP2014 is a next generation long-acting IFNa-2b, consisting predominantly of only one isoform as opposed to other commercially available pegylated interferons. AOP2014 is expected to have pharmacokinetic and pharmacodynamic profiles which may allow a reduced dosing frequency compared to other pegylated IFNs, potentially leading to improved tolerability, better compliance, and, finally, favourable long-term treatment outcomes. Study design. This is an open-label, prospective, multicentre, phase I/II dose escalation study of AOP2014 to determine the maximum tolerated dose (MTD), safety and efficacy in PV. Inclusion criteria are: age ≥18 years, confirmed diagnosis of PV (WHO, 2008, or the PSVG plus JAK2 positivity). Both newly diagnosed and pre-treated (cytoreduction) patients are eligible; hydroxyurea (HU) is allowed until the first application of AOP2014. If abnormally elevated prior to entry, sustained hematocrit (Hct) ≤45% is to be achieved by phlebotomy prior to the first administration. 3+3 dose escalation with cohort extension after MTD definition is being utilized. Intra-patient dose escalation to the dose level, previously established to be safe, is encouraged. MTD is defined as the highest dose level at which no more than 1 of 6 subjects experience a DLT during the first treatment period (2 weeks). Complete hematological response (CR) is defined by Hct

Description: Introduction: In Multiple Myeloma immune dysregulation with quantitative and qualitative changes in T-cell subpopulations is thought to result in a reduced anti-tumour immune response promoting disease progression. Methods: A retrospective cohort of 45 myeloma patients was analyzed for the extent of tumor infiltrating CD4+ and CD8+ lymphocytes by means of immunohistochemistry using sophisticated automated evaluation software. Results: Here, for the first time we analyzed trephine biopsies of myeloma patients and we report a significant association of different patterns of immune cell infiltrations with OS and PFS suggesting that these patients might particularly benefit from immune modulating therapeutic strategies: CD4+ T-cells below a cutoff of 0.28% lymphocytes/total nucleated cells were associated with a significantly longer overall survival, while CD8+ T-cells above the cutoff of 6.51% predicted a longer progression free survival. Treatment with immunomodulatory drugs resulted in a significantly better overall- and progression free survival for patients with adverse local immunological features compared to those treated with proteasome inhibitors or non-novel agents. We suggest that immune dysregulation in myeloma significantly influences overall- and progression free survival. We will now validate this immuno algorithm of lymphocyte infiltration patterns as a predictive biomarker of IMiD responsiveness in the framework of a large randomized phase III trial. If confirmed they might be used as a putative biomarker to guide rational therapy allocation in the future. Disclosures Willenbacher: Celgene: Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Willenbacher:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; European Commision: Research Funding.

Description: Background AOP2014 is a next generation long-acting pegylated IFN-alpha-2b, consisting predominantly of only one isoform, as opposed to other commercially available pegylated interferons. Due to this property, reduced dosing frequencies, better tolerability, improved compliance and more favorable long-term treatment outcomes in patients with Polycythemia Vera (PV) are expected. The drug has Orphan designation by EMA and FDA and is currently in the phase III stage of development. Study design This phase I/II single arm dose escalation study with cohort extension included 51 patients with PV who could be either cytoreduction therapy naive or pre-treated. AOP2014 was administered subcutaneously in a dose range of 50-540 mcg every two weeks. Main objectives were to define the maximum tolerated dose as well as observe the long term safety and efficacy in terms of normalization of blood parameters and molecular abnormalities (results were already presented at the ASH 2013 annual meeting by Gisslinger et al). The option to switch to an "once every four weeks" schedule has been implemented by the amended protocol for patients who responded well to the treatment and participated in the study for longer than one year. The dose of the study drug had to remain unchanged after the switch, resulting in a decrease (by approx. the half) of the overall exposure to the drug. Outcomes of this switch are presented here. Results Patients (period A, median exposure duration 34 weeks, mean monthly dose 484 mcg) were dosed every two weeks based on the Phase II dosing rules prior having switch option. 33 patients (period B, median exposure duration 12 weeks, mean monthly dose 413 mcg) were dosed every two weeks beyond the first year and, showing benefit from treatment, have been assessed as eligible for switch. 28 patients (period C, median exposure duration 42 weeks) were then switched to once every four weeks schedule (mean monthly dose 221 mcg). Blood parameters were normalized and remained stable following one year of treatment and could be maintained after the switch (hematocrit, median,% - period A: 43, period B: 43, period C: 42; WBC, median, G/l - period A: 6.1, period B: 5.9, period C: 5.7; platelets, median, G/l - period A: 246, period B: 211, period C: 204). Spleen length stayed stable within the normal range following the switch in the majority of patients either (mean, in cm – period A: 11.4, period B: 8.3, period C: 10.3). Complete response as best individual response could be maintained in 42% from the period A, 55% in the period B and 67% of the period C patients, while for the partial hematological responders the results were 60%, 71% and 67%, respectively. Molecular response improved continuously over time, being maintained at the best individual level in 31% of period A patients, compared to 42% of period B and 75% of period C patients. Decrease of application frequency and total dose exposure led to decrease of the occurrence of all/drug related AEs (measured as mean count of adverse events [AE] per patient week exposure) to 0.17/0.09 (arm A) from 0.3/0.09 (arm B) and 0.08/0.03 (arm C). Conclusions This explorative data from endpoints pre-defined in the prospective study demonstrate the feasibility to further reduce the frequency of AOP2014 administration to once every four weeks in responding patients, previously treated every two weeks. Reduced injection frequency is not associated with a lack of- response, but clearly improves tolerability. Finally, continuous reduction of the JAK2 allelic burden indicates that duration of interferon exposure rather than dose of interferon is an important variable inducing molecular responses. The here presented findings support the idea that interferon alpha effects in PV are pleiotropic, such as induction of immune-surveillance, which is continuously maintained at lower AOP2014 levels. Disclosures Gisslinger: AOP Orphan Pharmaceuticals AG: Research Funding. Buxhofer-Ausch:AOP Orphan Pharmaceuticals AG: Research Funding. Thaler:AOP Orphan Pharmaceuticals AG: Research Funding. Schloegl:AOP Orphan Pharmaceuticals AG: Research Funding. Gastl:AOP Orphan Pharmaceuticals AG: Research Funding. Wolf:AOP Orphan Pharmaceuticals AG: Research Funding. Kralovics:AOP Orphan Pharmaceuticals AG: Research Funding. Gisslinger:AOP Orphan Pharmaceuticals AG: Research Funding. Strecker:AOP Orphan Pharmaceuticals AG: Research Funding. Egle:AOP Orphan Pharmaceuticals AG: Research Funding. Melchardt:AOP Orphan Pharmaceuticals AG: Research Funding. Burgstaller:AOP Orphan Pharmaceuticals AG: Research Funding. Willenbacher:AOP Orphan Pharmaceuticals AG: Research Funding. Zoerer:AOP Orphan Pharmaceuticals AG: Employment. Kadlecova:AOP Orphan Pharmaceuticals AG: Consultancy. Zagrijtschuk:AOP Orphan Pharmaceuticals AG: Employment. Klade:AOP Orphan Pharmaceuticals AG: Employment. Greil:AOP Orphan Pharmaceuticals AG: Research Funding.

Description: Introduction: Most indolent NHL patients (pts) have advanced stage disease at diagnosis, and no curative therapy exists. The mainstay of both first- and second-line (2L) therapy is anti-CD20 chemo-immunotherapy, and although initially effective, most pts relapse, with median PFS decreasing markedly after 2L and 3rd-line therapies. In addition, many pts eventually develop resistance to rituximab (RTX)/RTX-containing regimens, thus therapeutic targets other than CD20 are important. Those who develop resistance to RTX, especially the elderly, need new treatment approaches. With a median age at diagnosis of 67 (seer.gov), NHL is a disease of the elderly, who are at risk of developing cumulative myelosuppression, cardiac toxicity, and severe infections with currently available therapies. CD37 is highly expressed (〉90%) in B-cell NHL, providing an alternative target to CD20. Lutetium (177Lu) lilotomab satetraxetan (Betalutin®) is a beta-emitting anti-CD37 ARC in a ready-to-use formulation. LYMRIT 37-01 is a phase I/II open-label, multicenter, dose-escalation study to determine the safety, pharmacokinetics (PK), and preliminary efficacy of a single dose of Betalutin in pts with relapsed iNHL, and to establish a recommended phase II dose (RP2D). We present updated efficacy and safety data for the phase I/IIa part of the study (Part A) as of 22 June 2018; all pts have ≥ 6 months (m) of follow-up, except for 3 (will be completed in August). Methods: Pts with histologically confirmed iNHL relapsing after ≥1 prior therapy with 150 x 109/L, no prior SCT/RIT, and a life expectancy of ≥3 months were enrolled into 1 of 4 dose-escalation arms (Part A) to determine the optimal lilotomab pre-dose and Betalutin dose for further evaluation in an expanded phase II cohort. A fifth arm collected additional PK data. All pts received pre-treatment with RTX. Responses were assessed using Cheson IWG response criteria (including CT and FDG PET/CT scans) beginning at week 12. Results: 74 pts [57 follicular (FL), 7 mantle cell (MCL), 9 marginal zone (MZL), 1 small lymphocytic (SLL)] were enrolled at 13 sites from Dec 2012 to Feb 2018. Median age was 68 (range 38-87; 55% ≥ 65); the median no. of prior therapies was 3 (range 1-9); 48 pts (65%) had received ≥2 prior therapies. Two RP2Ds emerged: a lilotomab pre-dose of 40 mg + 15 MBq/kg Betalutin ("40/15"; Arm 1) and a lilotomab pre-dose of 100 mg/m2 + 20 MBq/kg Betalutin ("100/20"; Arm 4). For all pts, the overall response rate (ORR) was 61%, with 26% complete responses (CR). By subtype, the ORR was 65% (CR 24%) for FL, and 78% (CR 44%) for MZL. FL with ≥2 prior therapies (n=37) had an ORR of 70% (CR 27%). With a median follow-up of 9.1 m (range 4.9-49.5 m), the median duration of response for all pts is 13.3 m (20.5 m for those with a CR); 26 pts (35%) have remained free of disease progression for 〉12 m [CR(15)/PR(5)/SD(6)]. For the 36 pts receiving the "40/15" regimen, the ORR was 58% (CR 28%), and 64% (CR 28%) for FL (n=25). The ORR was 63% (CR 21%) for 19 pts receiving the "100/20" regimen, and 69% (CR 19%) for FL (n=16). Betalutinwas well-tolerated. The most common grade (G) 3/4 AEs were neutropenia (53%) and thrombocytopenia (48%); 5 pts (7%) had G3/4 infections (pneumonia, UTI, pharyngitis (G3), 2 G4 sepsis). No febrile neutropenia was reported. Four pts had plt transfusions [low plt count (2), epistaxis (1), hematuria (1)]; 3 received G-CSF. Two pts had infusion reactions; both were related to RTX. SAEs occurred in 14 pts (19%); SAEs in ≥2 pts were atrial fibrillation, thrombocytopenia, lymphoma progression and sepsis (all n=2). Five pts developed transient anti-drug antibodies. One case of CMML occurred 24 m after Betalutin (18 m after subsequent bendamustine-RTX therapy). There were no study drug-related deaths in the treatment period. G3/4 neutropenia and thrombocytopenia occurred in 56%/56% (40/15 regimen) and 47%/42% (100/20 regimen). Conclusions: Betalutin is well tolerated and has promising antitumor activity in recurrent iNHL, especially in FL and MZL. Use of a higher lilotomab pre-dose resulted in a lower incidence of G3/4 hematologic AEs. With a single administration, Betalutin has the potential to be a novel, safe, and effective therapy for pts with B-cell malignancies. The 2 RP2Ds from Part A of the study are now being compared in a randomized phase 2b cohort (Part B: "PARADIGME") in relapsed, RTX/anti-CD20 refractory FL pts who have received ≥2 prior therapies. Disclosures Kolstad: Nordic Nanovector: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Roche: Research Funding. Illidge:Nordic Nanovector: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Research Funding; Takeda: Consultancy, Honoraria. Hajek:Amgen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding. Jurczak:European Medicines Agency: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Consultancy; Acerta: Consultancy, Research Funding; Sandoz-Novartis: Consultancy; Afimed: Research Funding; Bayer: Research Funding; BeiGene: Research Funding; Celgene: Research Funding; Epizyme: Research Funding; Gilead: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Nordic Nanovector: Research Funding; Merck: Research Funding; Morphosys: Research Funding; Pharmacyclics: Research Funding; Servier: Research Funding; Roche: Research Funding; TG Therapeutics: Research Funding. Rojkjaer:Nordic Nanovector: Employment. Østengen:Nordic Nanovector: Employment.

Description: Purpose (1)To give an overview on published decision-analytic models evaluating treatment strategies in multiple myeloma with a focus on methodological aspects of modeling approaches. (2) To derive recommendations for future decision-analytic models analyzing different treatment regimens for multiple myeloma patients. Methods A systematic literature search was performed in the electronic databases Pubmed, NHS EED and the Tufts CEA Registry to identify studies evaluating multiple myeloma treatment strategies using mathematical decision-analytic models. To meet the inclusion criteria, models were required to compare different treatment strategies, to be published as full text articles in English, and comprise relevant clinical health outcomes (e.g., responses, progression-free survival, or QALYs) over a defined time horizon and population. Evaluation of costs was optional. We used evidence tables to summarize methodological characteristics, such as modeling approach and validation, simulation technique, health outcomes evaluated, included states/events, perspective, time horizon and uncertainty analysis. Results We found eleven decision-analytic modeling studies. Economic evaluations were included in all studies. The modeling approaches applied included a decision tree model, Markov cohort model, discrete event simulations, partitioned survival analyses and area under the curve models. Time horizons ranged from seven years to lifetime. Six models adopted the perspective of the health care system, three a third party payer, two the government payer and only one the societal perspective. Health outcomes included (overall, median, progression-free) survival, number needed to treat, time to discontinuation of treatment, life expectancy, and QALYs. Evaluated treatment strategies included lenalidomide, dexamethasone, bortezomib, melphalan, prednisone, thalidomide, haemodialysis, bone marrow transplantation, zoledronic acid, and clodronate. Health states used in the models were mainly either not progressed, progressed and death, or some authors also took into account the hematological response to therapy (partial, complete). In most studies, model validation was only mentioned in the discussion when comparing the results with other cost-effectiveness studies. All authors performed deterministic sensitivity analyses. Additionally, seven articles reported a probabilistic sensitivity analysis. Conclusions We identified several well-designed models for different multiple myeloma treatment strategies evaluating relevant health outcomes as well as economic parameters. However, the quality of reporting varied considerably and in some cases the models were not sufficiently described. For the future, we recommend an explicit model description including all relevant parameters and model validation using independent data. This work was supported by the COMET Center ONCOTYROL, which is funded by the Austrian Federal Ministries BMVIT/BMWFJ (via FFG) and the Tiroler Zukunftsstiftung/Standortagentur Tirol (SAT). Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 175 AOP2014 is a next generation long-acting pegylated IFNa-2b, consisting predominantly of only one isoform, as opposed to other commercially available pegylated interferons. AOP2014 has a distinct pharmacokinetic and pharmacodynamic profile which may potentially allow reduced dosing frequencies compared to other pegylated IFNs. This is being expected to result in improved tolerability, better compliance, and, finally, favorable long-term treatment outcomes. AOP2014 is a designated Orphan Drug in EU for treatment of patients with PV. The maximum tolerated dose (MTD), long term safety and efficacy of AOP2014, administered subcutaneously every 14 days, are the main objectives of the study. Patients with confirmed PV diagnosis, age equal or older 18 years, both naïve and cytoreduction pre-treated are eligible. After establishing the MTD, an extended cohort of 25 additional patients was planned to be recruited. European LeukemiaNet criteria were used for response assessment. 34 patients, treated by March 31, 2012 were included into this analysis: 25 in Phase I (dose-finding) and 9 in the Phase II (cohort extension). Median time from diagnosis was 24 months (range 0–180). 12 patients (35%) were HU pre-treated (mean past duration of HU pre-treatment 39 months, mean daily HU dose 950 mg). Median number of phlebotomies in the past 3 months prior to inclusion was 1 (range 0–8), a total of 21 patients (62%) were regularly phlebotomized at least once in three months prior to study entry. 11 patients (32%) had a history of thrombotic complications. Median Hct at baseline was 42% (range 36–51). Median WBC and platelet counts were 10.6*109/l (range 3.9–20.4) and 452*109/l (range 141–1019), respectively. 17 patients (50%) had splenomegaly at baseline. The median reported treatment duration was 41 weeks (range: 1 day – 80 weeks), 11 patients completed 1 year on treatment. Doses from 50 to 540 ug every two weeks were tested, 540 ug has been concluded as MTD as the highest tested dose, since no DLTs occurred in the study. The mean administered dose (both Phase I and II patients) was 287 ug. After 28 weeks of treatment (21 evaluable patients), 71% of patients had hematological response (7 CR, 33%; 8 PR, 38%), at week 36 (19 evaluable patients) 8 patients (42%) achieved a CR and 8 patients (42%) a PR, overall response rate (ORR, CR+PR) was 84%. At week 52 (1 year; 11 evaluable patients), 5 patients (46%) had CR and 5 (46%) PR, ORR was 91%; 8 (73%) patients presented with completely normalized blood values, all evaluable patients were phlebotomy free at this timepoint. 4 patients (of 12 evaluable for this measurement, 33%) had still enlarged spleen at week 52. At week 76, 2 evaluable patients were complete responders. At week 52, 1 patient (of 9 evaluable, 11%) developed partial molecular response, at week 68 3 patients (of 7 evaluable, 43%) had partial molecular response. One patient with allelic burden of 22% at baseline developed complete molecular response at week 36 (still ongoing). Mainly grade 1 and 2 adverse events were reported. A total of 358 adverse events occurred. 27 patients (79%) suffered from drug-related adverse events. 9 patients (26%) developed serious adverse events; 4 SAEs were considered to be treatment related. 5 patients (15%) discontinued their study participation prematurely, 3 of them due to adverse events (deterioration of underlying disease and two cases of depression). Acceptable tolerability and durable clinical benefits have been demonstrated in PV patients measured as overall response rate of above 90% with CRs of 46% at one year after treatment start. Phlebotomy independence and normalization of hematological parameters could be seen in most of the patients. The study continues to recruit and collect long term follow up information. Presented data support further development of AOP2014 in PV, a Phase III study is planned to start early 2013. Disclosures: Gisslinger: AOP Orphan Pharmaceuticals AG: Research Funding; Novartis: Speakers Bureau; Celgene Austria: Research Funding, Speakers Bureau. Kralovics:AOP Orphan Pharmaceuticals AG: Research Funding. Gisslinger:AOP Orphan Pharmaceuticals AG: Research Funding. Lechner:AOP Orphan Pharmaceuticals AG: Research Funding. Buxhofer-Ausch:AOP Orphan Pharmaceuticals AG: Research Funding. Strecker:AOP Orphan Pharmaceuticals AG: Research Funding. Gastl:AOP Orphan Pharmaceuticals AG: Research Funding. Willenbacher:AOP Orphan Pharmaceuticals AG: Research Funding. Greil:AOP Orphan Pharmaceuticals AG: Research Funding. Egle:AOP Orphan Pharmaceuticals AG: Research Funding. Melchardt:AOP Orphan Pharmaceuticals AG: Research Funding. Burgstaller:AOP Orphan Pharmaceuticals AG: Research Funding. Schloegl:AOP Orphan Pharmaceuticals AG: Research Funding. Tarmann:AOP Orphan Pharmaceuticals AG: Employment. Zoerer:AOP Orphan Pharmaceuticals AG: Employment. Klade:AOP Orphan Pharmaceuticals AG: Employment. Zahriychuk:AOP Orphan Pharmaceuticals AG: Employment. Thaler:AOP Orphan Pharmaceuticals AG: Research Funding.

Description: Background AOP2014/P1101 is a novel, investigational mono-pegylated proline-interferon alpha-2b. In contrast to other pegylated IFNs, AOP2014/P1101 consists of one predominant isoform. AOP2014/P1101 has Orphan Drug Designation in EU and USA for treatment of patients with PV. Study design Long term efficacy and safety data are being collected in the follow-up extension stage of the study (collecting the data of both Phase I and Phase II portions of the study), after the maximum tolerated dose (MTD) of AOP2014, administered subcutaneously every 14 days, has been defined earlier. Patients with confirmed PV diagnosis, age ≥18 years, both naïve and cytoreduction pre-treated were eligible. After establishing the MTD, an extended cohort of 25 additional patients has been planned to be recruited. Complete hematological response (CR) is defined by Hct 50% mutant allele burden. Results Study completed recruitment late 2012, after inclusion of 51 patients. Data on treatment by March, 31, 2013, are covered by the current analysis. Median time from diagnosis to inclusion was 2 years (Q1-Q3: 1.0-6.0). 20 patients (39%) were pre-treated with HU prior to study entry. Median number of phlebotomies in the past 3 months prior to inclusion was 1 (range 0–8), a total of 31 patients (61%) were regularly phlebotomized at least once in three months prior to study entry. 11 patients (22%) had a history of thrombotic complications. Median Hct at baseline was 43% (Q1-Q3: 41-44). Median WBC and platelet counts were 11.1*109/l (Q1-Q3: 9.3–13.6) and 415*109/l(Q1-Q3: 316-583), respectively. 17 of 46 (67%) evaluable patients had spleen 〉12cm in length at baseline (by ultrasound). Median JAK2 allelic burden at baseline was 48% (Q1-Q3: 29-71). The median reported treatment duration is 345 days, 25 patients completed were followed up for at least one year. After six months of treatment (35 evaluable patients), 60% of patients had hematological response (9 CRs, 26%; 12 PR, 34%). At one year (25 evaluable patients), 9 patients (36%) had CR and 10 (40%) had PR, resulting in an ORR of 76%. At 18 months (n=19), there were 9 CRs (47%) and 8 PRs (42%), resulting in an ORR of 89%. At months 6, 12 and 18; 6 (19%), 1 (4%) and 1 (5%) patients were still in need of phlebotomy, respectively. The percentage of patients with enlarged spleen (〉12cm in length) decreased to 56% at the end of the first treatment year. Mean JAK2 allelic burden dropped to 44% at both 6 months (7/29% mPRs) and 12 months (6/22%), while at 18 month the mean value was 25% (2 of 3 evaluable patients were in PR); decrease of allelic burden was more profound in the arm of HU naïve patients. 645 adverse events (AE) were reported in 48 (94%) patients, half of them (296; 46%) were drug-related and 26 (4%) serious. The following AEs were reported in 〉20% of the patients: pruritus, headache, fatigue, arthralgia, diarrhea and vertigo. AE related patient discontinuation occurred in 10 (20%) patients; two patients left the study due to administrative reasons; violation of eligibility criteria, lack of efficacy and administrative reasons led to withdrawal in one case per category, respectively. 87 events (13%) mandated dose reduction or delay. Conclusions The more convenient, every 14 days treatment schedule is feasible and effective. Efficacy and safety profile remain in line with expectations from other (pegylated) interferons. ORR of 〉80% with cumulative CRs 45-50%, accompanied by phlebotomy independence, normalization of hematological parameters and spleen size reduction in majority of patients has been observed. Significant and sustained JAK2 allelic burden decrease, starting from week 28 of treatment, was seen. The results support further development of AOP2014/P1101 in PV; accordingly, a phase III clinical study (PROUD-PV) is starting to recruit patients in Q4 2013. Disclosures: Gisslinger: AOP Orphan Pharmaceuticals AG: Research Funding. Buxhofer-Ausch:AOP Orphan Pharmaceuticals AG: Research Funding. Thaler:AOP Orphan Pharmaceuticals AG: Research Funding. Schloegl:AOP Orphan Pharmaceuticals AG: Research Funding. Gastl:AOP Orphan Pharmaceuticals AG: Research Funding. Wolf:AOP Orphan Pharmaceuticals AG: Research Funding. Kralovics:AOP Orphan Pharmaceuticals AG: Research Funding. Gisslinger:AOP Orphan Pharmaceuticals AG: Research Funding. Lechner:AOP Orphan Pharmaceuticals AG: Research Funding. Strecker:AOP Orphan Pharmaceuticals AG: Research Funding. Egle:AOP Orphan Pharmaceuticals AG: Research Funding. Melchardt:AOP Orphan Pharmaceuticals AG: Research Funding. Burgstaller:AOP Orphan Pharmaceuticals AG: Research Funding. Willenbacher:AOP Orphan Pharmaceuticals AG: Research Funding. Zoerer:AOP Orphan Pharmaceuticals AG: Employment. Zahriychuk:AOP Orphan Pharmaceuticals AG: Employment. Klade:AOP Orphan Pharmaceuticals AG: Employment. Greil:AOP Orphan Pharmaceuticals AG: Research Funding.

Description: Key Points The novel IFNα-2b, ropeginterferon alfa-2b, administered once every 2 weeks has low toxicity and induces high and sustained response rates in polycythemia vera patients. Ropeginterferon alfa-2b induces significant partial and complete molecular response rates, as reflected by reduction of JAK2 allelic burden.