ALBERT

Description: Background Ropeginterferon alfa-2b (AOP2014/P1101) is a novel long-acting pegylated IFN-alpha-2b, composed of mainly one isoform, resulting in longer half-life and exposure time. 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 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 ropeginterferon alfa-2b, administered subcutaneously every 14 to 28 days, has been defined earlier. Patients with confirmed diagnosis of PV, age ≥18 years, both naïve and cytoreductively 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 hematocrit (Hct) 50% mutant allele burden. The present analysis was focused on long-term tolerability and safety in correlation with the dose of ropeginterferon alfa-2b in PV. Results Data on treatment as by July, 24, 2015, are covered by the current analysis. Baseline characteristics of the study cohort during short-term treatment were already presented earlier (Gisslinger et al, ASH 2013). The full analysis set and efficacy set were composed of 51 and 47 patients, respectively. Currently, the median reported treatment duration is 138 weeks, 33 patients completed their follow up for two years, 19 for three years. Starting with the week 10, Hct-level, platelet- and WBC-counts could be constantly maintained within normal range in the majority of patients. In a group of patients with the mean administered dose of 300 µg, n=11) group of 8 (73%) and 3 (27%) respectively. However, no statistical significance can be observed if correlation between the dose and response status was analyzed. 30 patients are still being treated in the study. Similarly, no association between the dose and occurrence of adverse events in the study could be observed. Complete molecular response as best individual response was observed more frequently in the high dose group 4 (36%) compared to 8 (23%) in the low dose group, while partial molecular responses were equally frequent in both dose groups (in 6/55% and 20/57%, respectively). 21 patients discontinued the study, 18 being treated with AOP2014 doses corresponding to low, and 3 to the high dose arms, corresponding to the drop-out rate of 50% and 27% in the respective arms. Interestingly, all discontinuations in the high dose group occurred within the first year of treatment (at weeks 16, 18 and 32), while the drop-outs in the low dose group (6 patients, 33%) discontinued the study after completion of their first year of treatment. Conclusions Efficacy and safety profile remain in line with expectations from other (pegylated) interferons. Overall response rate of 〉80% with cumulative CRs in 45-50%, accompanied by phlebotomy independence, normalization of hematological parameters and spleen size reduction in majority of patients have been observed. Significant and sustained JAK2 allelic burden decrease, starting from week 28 of treatment, was seen. No significant difference between the two mean dose levels regarding response rates or adverse events even during long-term treatment and observation could be observed. These finding are to be further verified in a larger prospective setting. Disclosures Gisslinger: Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau; AOP ORPHAN: Consultancy, Honoraria, Research Funding, Speakers Bureau; Geron: Consultancy; Sanofi Aventis: Consultancy; Janssen Cilag: Honoraria, Speakers Bureau. Buxhofer-Ausch:AOP Orphan: Research Funding. Thaler:AOP Orphan: Research Funding. Schlögl:AOP Orphan: Research Funding. Gastl:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; AOP Orphan: Research Funding. Ban:AOP Orphan: Research Funding. Egle:AOP Orphan: Research Funding. Melchardt:AOP Orphan: Research Funding. Burgstaller:AOP Orphan Pharmaceuticals: Honoraria, Research Funding; Novartis: Honoraria; Mundipharma: Honoraria; Celgene: Consultancy, Honoraria, Research Funding. Willenbacher:COMET Center ONCOTYROL: Research Funding; AOP Orphan: Research Funding. Kralovics:AOP Orphan: Research Funding; Qiagen: Membership on an entity's Board of Directors or advisory committees. Zörer:AOP Orphan: Employment. Ammann-Mwathi:AOP Orphan: Employment. Kadlecova:AOP Orphan: Consultancy. Zagrijtschuk:AOP Orphan: Employment. Klade:AOP Orphan: Employment. Greil:Pfizer: Honoraria, Research Funding; GSK: Research Funding; Boehringer-Ingelheim: Honoraria; AOP Orphan: Research Funding; Celgene: Consultancy; Janssen-Cilag: Honoraria; Genentech: Honoraria, Research Funding; Novartis: Honoraria; Astra-Zeneca: Honoraria; Amgen: Honoraria, Research Funding; Ratiopharm: Research Funding; Sanofi Aventis: Honoraria; Merck: Honoraria; Mundipharma: Honoraria, Research Funding; Eisai: Honoraria; Cephalon: Consultancy, Honoraria, Research Funding; Bristol-Myers-Squibb: Consultancy, Honoraria; Roche, Celgene: Honoraria, Research Funding.

Description: Introduction Plasma cell leukemia (PCL) is a leukemic variant of Myeloma arising either de novo or from clinically pre-existent Multiple Myeloma (MM). Treatment options are limited and no drug has ever been explicitly registered in this indication. Furthermore, there is no generally accepted standard of care, although most haematologists would, depending on previous treatments, use combinations of MM drugs and chemotherapy as induction therapy. Pixantrone (PIX) is an aza-anthracenedione which has both alkylating and intercalating activity as well as a unique method of action the induction of cell death through mitotic perturbations and subsequent aberrant cell divisions. PIX is registered in both the US and EC for the treatment of relapsed or refractory aggressive NHL that has failed to respond to at least two previous regimens. Our group has previously shown significant in-vitro activity of PIX in both MM cell lines and primary patient materials*. Methods Peripheral blood mononuclear cells from patient samples containing 〉 80% plasma cells at high leucocyte counts were isolated by density gradient using Ficoll and incubated for 24 and 48h with various pharmacokinetically realistic concentrations of PIX ranging from 0.01 – 5.00 µM at 37°C in a humidified air atmosphere. Apoptosis was determined by annexin/propidium iodide staining of the whole population (Pt. 1) and 7-AAD staining of the CD38 high/CD45 low cells on a FACSCanto using Diva software (BD). Cases Pt 1. was a 63 year old female diagnosed MAR 2012 with an IgG lambda ISS stage I, Durie & Salmon stage III A MM. Cytogenetics showed a t(11;14). 1st line treatment consisted of VTD -〉 ASCT with a resulting PR. Post ASCT the pt. was stable on Rd – maintenance until JAN 13 when a leukemic transformation and a light chain escape phenomenon occurred. Cytogenetics showed clonal evolution with acquisition of additional aberrations (+18, amp 1p36, amp 11q22.3). From APR 2013 – JUL 2013 the pt. could be stabilized with a Bortezomib-liposomal Anthracyclin-Dexamethason combination. On progression she opted for palliative care and succumbed to PCL in AUG 2013. Her PCL cells were evaluated in-vitro. Pt. 2 was a 51 years old female diagnosed with FLC kappa ISS stage III, Durie & Salmon stage III A MM in NOV 2011. In JUN 2014 the pt. presented with a 2nd relapse having been pre-treated with VTD-ASCT in 1st line, and Rd in 2nd line. Out of PR under continuous Rd for 9 months she developed a rapidly progressive PCL with a complex aberrant karyotype and massively elevated sFLC kappa. The patient was severely anaemic and thrombopenic from presentation onwards. Her PCL cells were evaluated in-vitro while treatment was initiated with the Pi-Po-D regime: Table 1 Pi-Po-D regime DRUG APPLICATION DOSAGE SCHEDULE REPETITION Pixantrone i.v. 50mg/m² d1-8-15 d28 Pomalidomide p.o. 4mg d1-21 d28 Dexamethason p.o. 40mg d1-4, 8,15 d28 In-Vitro-Results Pt. 1 showed a significant induction of apoptosis concomitantly with a reduction of living cells after an incubation period of 24h starting with a PIX concentration of 2.50 µM and with 1.0 µM at 48h (Table 2). Similar results were obtained with the cells of Pt. 2, despite methodological problems however, plasma cells proofed not to be as sensitive as the whole cell population. Abstract 5732. Table 2 In-Vitro activity of Pixantrone in pt. 1 Pixantrone Concentration (µM) Living cells after 24 h (%) Apoptotic cells after 24h (%) Living cells after 48h (%) Apoptotic cells after 48h (%) 0.00 95.85 04.15 97.35 02.65 0.01 96.15 03.85 96.45 03.55 0.05 95.05 04.95 96.75 03.25 0.10 93.35 06.65 95.70 04.30 0.25 90.75 09.25 93.70 06.30 0.50 85.40 14.60 84.25 15.75 1.00 79.95 20.05 61.10 38.90 2.50 31.30 68.70 06.65 93.35 5.00 00.15 99.85 05.00 99.70 Clinical course with Pi-Po-D in PCL Pt. 2 received the Pi-Po-D regime as no suitable clinical alternative was available and in-vitro data were promising. We noticed a sharp decline of sFLC (〉 30%/3weeks) and peripheral plasma cell counts within cycle I as early sign of clinical activity. Unfortunately the pt. had a severe fall while being grade IV CTC thrombopenic and died from unstoppable intracranial haemorrhage. Discussion Pixantrone shows promising in-vitro activity in PCL and MM* at pharmacologically realistic concentrations and first signs of clinical activity in combination therapy. In our opinion PIX deserves further pre-clinical and clinical evaluation in MM and PCL. *J Clin Oncol 32, 2014 (suppl; abstr e19569) Figure 1 Figure 1. Disclosures Off Label Use: Use of Pixantrone in Plasma Cell Leukaemia.

Description: Abstract 2889 Poster Board II-865 Introduction: Serum free light chain analysis (sFLCA) is a tool to monitor myeloma disease activity and treatment response, and stratify myeloma pts. to defined risk groups and has been incorporated into diagnostic guidelines[1]. Either the ratio of the free kappa/lambda light chains (FLCQ), the absolute value of the involved light chain (FLCi) or the difference of involved and uninvolved light chain (FLCD) may be used. While sFLCA is recommended , urine analysis (uFLCA) at the moment is not. To analyze whether results from sFLCA and uFLCA would potentially have translated into altered clinical decision making and timing of treatments compared to classical paraprotein measurements (sPPM) in a cohort of myeloma patients we analyzed all measurements routinely performed at Innsbruck University Hospital between MAR 03 and OKT 08 and correlated them to individual pts. clinical courses. Methods: 187 pts. (109 m, 78 f) out 235 pts. identified were deemed eligible. Myeloma subtypes were IgG (57.2%), IgA (21,9%), light chain only (13.9%), IgM (3.2%), oligo and nonsecretory (2.6 %, incl. 2 pts. completely asecretory), and IgD (1,0%). 4 pts. were complete immunoglobulin only secreters. According to mSMART 15% were high risk, 61% standard risk and 23,5% of unknown category. In this cohort 3202 sFLCa, 1136 uFLCa and 2583 sPPM were performed (range 2-89, median 12). This measurements were correlated with 167 treatment lines applied in this pts. (49 auto-transplants, 3 allo-transplants, 7 auto/allo procedures, 68 regimes containing novel agents and 40 conventional chemotherapeutic approaches. Patients, Assays and Treatment Lines: 187 pts. (109 m, 78 f) out 235 pts. identified were deemed eligible. Myeloma subtypes were IgG (57.2%), IgA (21,9%), light chain only (13.9%), IgM (3.2%), oligo and nonsecretory (2.6 %, incl. 2 pts. completely asecretory), and IgD (1,0%). 4 pts. were complete immunoglobulin only secreters. According to mSMART 15% were high risk, 61% standard risk and 23,5% of unknown category. In this cohort 3202 sFLCa, 1136 uFLCa and 2583 sPPM were performed (range 2-89, median 12). This measurements were correlated with 167 treatment lines applied in this pts. (49 auto-transplants, 3 allo-transplants, 7 auto/allo procedures, 68 regimes containing novel agents and 40 conventional chemotherapeutic approaches. Results: sFLCa showed a significant advantage in detecting any of the predefined clinical endpoints (Table 1) . By using sPPM only , ∼ 40% of events would have been missed during the observation period. A median of 13% of the applied therapies proven to be ineffective could have been stopped and altered earlier on using the results of sFLCa. While the use of sFLCi and sFLCD resulted in comparable rates of false pos. and neg. results (Table 2) in comparison to sPPM, sFLCQ is more sensitive to effects of immunoparesis, changes of the uninvolved FLC concentration and renal function resulting in both more false pos., as well as false neg. results. sFLCa detected relapses with a median of 3 months prior to sPPM, therapeutic effectiveness with a median of 2 therapy cycles earlier than sPPM and therapeutic failure with a median of 1 antecedent cycle of therapy. Data on uFLCa will be provided at ASH. Discussion: This analysis proves sFLCa to be a useful tool in monitoring myeloma pts. clinical courses and the therapeutic effectiveness of myeloma treatment approaches, even in the setting of “real life medicine”. For monitoring purposes sFLCi and sFLCD should be used preferably due the higher false pos./neg. potential of sFLCQ . By using sFLCa in a structured diagnostic pathway treatment effectiveness could be judged earlier on and altered if necessary. Thus this analysis shows a potentially clinically significant benefit to myeloma pts. [1] Dispenzieri et al. Leukemia advance online publication 20 November 2008; doi:10.1038/leu.2008.307 Disclosures: No relevant conflicts of interest to declare.

Description: Introduction  Post-Transplant-Lymphoproliferative Disorders are well known known, but rare complications of solid organ or hematologic stem cell transplantations. Incidence after lung-transplantation [LU-TX] is estimated to be  ∼ 4.8% (Kremer et al. 2012). Most cases present as B-cell lymphomas (〉 90%)  and are EBV-associated. The WHO classification discriminates multiple subtypes (early lesions, monomorphic PTLD, polymorphic PTLD & classical Hodgkin lymphoma type PTLD). Treatment  options mirror this histologic diversity and range from reduction of immunosuppressive therapy only , to aggressive polychemotherapy, DLI  and second transplants. Patient history   In  May 2001 a left sided single LU-TX was performed for high grade bullous emphysema in a then 50 years old male patient. Several episodes  of organ rejection required the use of complex immunosuppressive combination therapies, but long-term pulmonary function was preserved and the patient could be tapered to Tacrolimus and low dose steroids for years.  Over the years the patient developed multiple severe comorbidities (Diabetes, renal retention, multiple pulmonary embolic events and peripheral thrombosis, as well as cardiac insuffiency and relapsing episodes of  pancreatitis). CIRS-G-severity index was 2.7/4 with an ECOG score of 3. In May 2013 the patient developed B-symptoms, cutaneous lesions and a predominantly inguinal and abdominal  lymphadenopathy. Histology & Staging   A lymph node excision biopsy showed a high grade T-Cell lymphoma (molecular and immunological features are sumarized in Table 1) which could be classified as ALK negative   anaplastic large cell lymphoma (ALCL) type PTLD, stage IV BE cutis  with additional high risk features (LDH elevation). Treatment  Because the patient was jugded to be unfit for aggresive polychemotherapy due to  multiple comorbidities and his lymphoma was found to be expressing the CD30 antigen strongly and uniformly  the anti-CD 30 immunotoxin Brentuximab-Vedotin (BV) was started at 1.8mg/m² every 21 days. B-symptoms disappeared within hours from the first infusion, palpable lymph nodes regressed within 3 weeks, and the patient improved to ECOG 1 in the same period. Furthermore  LDH normalized by cycle 2. A PET-CT scan after cycle 3 proved a first complete  metabolic remission and the treatment will be continued for 6 cycles. Data on response will be updated at ASH. No clinically relevant toxicities were observed. Conclusion  To our best knowledge this is the 1st report of the successful use of BV in a case of T-PTLD/ALCL  after SLU-TX. As this case illustrates Brentuximab-Vedotin  is a highly attractive , low toxicity treatment option in patients unfit to undergo aggressive polychemotherapy and can deliver complete responses with undeniable clinical benefit even in very advanced diease. For the rarity of these diseases the performance of a randomized clinical trial comparing BV to standard treatments seems unlikely for the foreseeable future and clinical decisions on treatment allocation have to be made on a case by case basis. We would recommend to at least  collect all cases of BV use in PTLD to improve the respective  best available evidence. Disclosures: Off Label Use: Brentuximab Vedotin for PTLD treatment.

Description: Background: Ropeginterferon alfa-2b (Ropeg) is a novel long-acting monopegylated IFN-alpha-2b. Due to reduced dosing frequencies, better tolerability and improved compliance, Ropeg may be a favorable treatment option for long-term therapy in patients with polycythemia vera (PV). Study design: PEGINVERA phase I/II (NCT: 2010-018768-18), a prospective, open-label, multicenter study, investigated the efficacy and safety of Ropeg for long-term treatment in 51 patients aged ≥18 years with a confirmed diagnosis of PV, regardless of prior cytoreductive therapy. Following ≥1 year of 2-weekly treatment, patients who responded well to Ropeg were permitted to switch to a 4-weekly dosing regimen. Results: Baseline characteristics of the study cohort and interim safety and efficacy data were presented previously (Gisslinger et al., Blood, 2015). Fifty-one patients were treated: Median exposure to Ropeg was approximately 5.1 years (61 months; range: 0 to 87 months). Patients were treated for a median of approximately 2 years (98.9 weeks; (Q1-Q3: 69.0 - 117.4 weeks) on the 2-weekly regimen and 4 years (207.1 weeks; Q1-Q3: 158.6 - 242.0 weeks) on the 4-weekly regimen. The best observed individual hematological response for patients in the efficacy analysis set (FAS) was a complete hematological response for 27/42 (64.3%) and a partial response for 14/42 (33.3%) patients. Patients required a median of 34 weeks (Q1-Q3: 10-96 weeks) treatment to achieve a complete hematological response, and 10 weeks (Q1-Q3: 10-20 weeks) to achieve any hematological response. Switch from 2 to 4-week dosing regimen had no apparent effect on maintenance of response. With respect to JAK-2 allele burden, the best observed individual molecular response was a complete response for 12/42 (28.6%) patients and a partial response for 19/42 (45.2%) patients. Lowest JAK-2 values relative to baseline are presented by patient in Figure 1. Patients required a median of 82 weeks (Q1-Q3: 44-115 weeks) treatment to achieve a complete molecular response and 34 weeks (Q1-Q3: 18-55 weeks) treatment to achieve any molecular response. Irrespective of dosing regimen, molecular responses tended to increase over time. Most patients reported at least one adverse reaction (AR) to treatment (409 ARs in 48/51 [94.1%]); however, the majority (296 in 44 [86.3%] patients) were mild; 102 (in 34 [66.7%] patients) were moderate and 11 (in 10 [19.6%] patients) were severe. The most frequently reported ARs (frequency 〉20%) were arthralgia, influenza-like illness and fatigue. Twelve serious treatment emergent adverse events (TEAE) reported by 8/51 patients (15.7%) were considered to be treatment related: 2 events of depression, 2 of positive anti-thyroid antibodies, and one each of acute stress disorder, increased antinuclear antibodies, arthralgia, atrial fibrillation, fatigue, influenza-like illness, pyrexia, and increased transaminases. 25 patients completed the trial. The majority of discontinuation due to TEAE (13/21 patients) occurred in the first year, when the recommended slow up-titration of Ropeg could not be applied because of the maximum-tolerated-dose design. After the first year, only 8 additional patients discontinued because of TEAE. Conclusions: The final results of this phase I/II study of Ropeg in patients with PV support the findings of the pivotal phase III clinical trial (Gisslinger et al., Blood 2015) with respect to safety and efficacy as determined by hematological, clinical and molecular parameters. In addition, these data provide evidence that treatment with Ropeginterferon alfa-2b for up to 7 years is efficacious, well-tolerated and disease-modifying at both the 2 week and 4 week maintenance treatment regimens. Disclosures Gisslinger: AOP Orphan Pharmaceuticals AG: Consultancy, Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Janssen Cilag: Consultancy, Honoraria; Shire: Consultancy, Honoraria. Kralovics:MyeloPro Diagnostics and Research GmbH: Equity Ownership. Krauth:BMS: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Greil:MSD: Honoraria, Research Funding; Merck: Honoraria, Research Funding; Sandoz: Honoraria, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra Zeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Research Funding; Janssen: Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees. Zoerer:AOP Orphan Pharmaceuticals: Employment. Empson:AOP Orphan Pharmaceuticals: Employment. Grohmann-Izay:AOP Orphan Pharmaceuticals AG: Employment. Klade:AOP Orphan Pharmaceuticals AG: Employment.

Description: Background Ropeginterferon alfa-2b (AOP2014/P1101) is a novel long-acting pegylated IFN-alpha-2b, consisting predominantly of only one isoform, leading to longer half-life and exposure time. 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 The PEGINVERA study (NCT01193699) is the phase I/II single arm dose escalation study with cohort extension after defining the MTD. 51 patients with PV who could be either cytoreduction therapy naive or pre-treated were included. Ropeginterferon alfa-2b was administered subcutaneously in a dose range of 50-540 µg every two weeks. Main objectives were definition of the maximum tolerated dose as well as observation long term safety and efficacy in terms of normalization of blood parameters and molecular abnormalities. 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 of the overall exposure to the drug. Outcomes of this switch are presented here. Results 44 patients (period A, median exposure duration 37 weeks, mean monthly dose 505 µg), eligible for the analysis, i.e. being treated in the maintenance setting, were dosed every two weeks based on the Phase II dosing rules prior the amendment. 33 patients (period B, median exposure duration 12 weeks, mean monthly dose 432 µg) were dosed every two weeks beyond the first year and, showing benefit from treatment, have been assessed as eligible for the switch. 28 patients (period C, median exposure duration 93 weeks) were then switched to dosing once every four weeks (mean monthly dose 203 µg). Blood parameters were normalized and remained stable following one year of treatment and could be maintained after the switch (hematocrit, median in % - period A: 42.7, period B: 42.9, period C: 42.8; WBC, median in G/l - period A: 5.6, period B: 5.3, period C: 5.8; platelets, median in G/l - period A: 252, period B: 217, period C: 210). Spleen length stayed stable within the normal range following the switch in the majority of patients (mean, in cm - period A: 11.6, period B: 8.8, period C: 11.1). Complete hematological response could be maintained in 57% of patients in period A, in 38% of patients in period B and in 50% of patients in period C, while for partial hematological responders the results were 71%, 54% and 57%, respectively. Molecular response improved continuously over time, being maintained at the best individual level in 38% of period A patients, compared to 53% of period B and 69% of period C patients. Comparison of patient discontinuations between the arms revealed the following rates: 5(11%) in the period A, 5(15%) in the period B and 3(11%) in the period C, while the mean numbers of adverse events per patient treatment week was 0.15, 0.27 and 0.09 respectively. There were no new drug-related SAEs occurring in the period C. Conclusions This explorative data re-confirm the feasibility to administer ropeginterferon alfa-2b once every four weeks, while efficacy was maintained compared to the biweekly application schedule. Reduced injection frequency is not associated with a lack or loss of response, but clearly improves tolerability. Finally, continuous reduction of the JAK2 allelic burden indicates that duration of interferon treatment rather than the absolute dose level 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 may be sufficiently maintained also at lower ropeginterferon alfa-2b levels. Disclosures Buxhofer-Ausch: AOP Orphan: Research Funding. Gisslinger:Geron: Consultancy; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; AOP ORPHAN: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau; Janssen Cilag: Honoraria, Speakers Bureau; Sanofi Aventis: Consultancy. Thaler:AOP Orphan: Research Funding. Schlögl:AOP Orphan: Research Funding. Gastl:AOP Orphan: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Kralovics:AOP Orphan: Research Funding; Qiagen: Membership on an entity's Board of Directors or advisory committees. Ban:AOP Orphan: Research Funding. Egle:AOP Orphan: Research Funding. Melchardt:AOP Orphan: Research Funding. Burgstaller:Celgene: Consultancy, Honoraria, Research Funding; Mundipharma: Honoraria; Novartis: Honoraria; AOP Orphan Pharmaceuticals: Honoraria, Research Funding. Willenbacher:AOP Orphan: Research Funding. Zörer:AOP Orphan: Employment. Ammann-Mwathi:AOP Orphan: Employment. Kadlecova:AOP Orphan: Consultancy. Zagrijtschuk:AOP Orphan: Employment. Klade:AOP Orphan: Employment. Greil:Novartis: Honoraria; Astra-Zeneca: Honoraria; Boehringer-Ingelheim: Honoraria; Sanofi Aventis: Honoraria; GSK: Research Funding; Celgene: Consultancy; Pfizer: Honoraria, Research Funding; Roche, Celgene: Honoraria, Research Funding; Bristol-Myers-Squibb: Consultancy, Honoraria; Cephalon: Consultancy, Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Eisai: Honoraria; Mundipharma: Honoraria, Research Funding; Merck: Honoraria; Janssen-Cilag: Honoraria; Genentech: Honoraria, Research Funding; Ratiopharm: Research Funding; AOP Orphan: Research Funding.

Description: Multiple myeloma (MM), the second most common hematologic malignancy, is characterized by the clonal expansion of plasma cells. Despite dramatic improvements in patients′ survival over the past decade due to advances in therapy exploiting novel molecular targets (immunomodulatory drugs, proteasome inhibitors and monoclonal antibodies), the treatment of relapsed and refractory disease remains challenging. Recent studies confirmed complex, dynamic, and heterogeneous genomic alterations without unifying gene mutations in MM patients. In the current review, we survey recent therapeutic strategies, as well as molecular profiling data on MM, with emphasis on relapsed and refractory cases. A critical appraisal of novel findings and of their potential therapeutic implications will be discussed in detail, along with the author’s own experiences/views.

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Description: Cancer patients frequently use complementary medicine. Curcumin (CUR) and its derivates (from the extract of Curcuma longa L.) represent some of the most frequently used ones, having a long history in traditional Asian medicine. CUR was demonstrated, both in vitro and in vivo, to have significant anti-inflammatory effects, thus potentially counteracting cancer-promoting inflammation, which is a hallmark of cancer. CUR modulate a plethora of signaling pathways in cancer cells, comprising the NF-κB (nuclear factor k-light-chain-enhancer of activated B cells), the JAK/STAT (Janus-Kinase/Signal Transducers and Activators of Transcription), and the TGF-β (transforming growth factor-β) pathways. Furthermore, CUR confers properties of electron receptors, which destabilize radical oxygen species (ROS), explaining its antioxidant and anti-apopototic effects. Although CUR has a low bioavailability, its role in advanced cancer treatment and supportive care was addressed in numerous clinical trials. After promising results in phase I–II trials, multiple phase III trials in different indications are currently under way to test for direct anti-cancer effects. In addition, CUR exerts beneficial effects on cancer treatment-related neurotoxcity, cardiotoxicity, nephrotoxicity, hemato-toxicity, and others. More efficient galenic formulations are tested to optimze CUR’s usability in cancer treatment. This review should provide a comprehensive overview of basic science, and pre-clinical and clinical data on CUR in the field of oncology.