ALBERT

Beschreibung: Abstract 2844 Background: Myeloproliferative neoplasms, including PMF, PET-MF, and PPV-MF, are a group of clonal stem cell–derived diseases characterized by bone marrow fibrosis, splenomegaly, and debilitating constitutional symptoms. Ruxolitinib (rux), a potent oral JAK1 & 2 inhibitor, demonstrated rapid and durable reductions in splenomegaly and improved MF-related symptoms and quality of life in 2 phase 3 studies (COMFORT-I and -II). Due to unmet medical need, rux has been made available through an individual patient supply program (IPSP) outside the US. Methods: Patients (pts) with PMF, PPV-MF, or PET-MF requiring treatment (as determined by their physician) and classified as high-, intermediate (int)-2–, or int-1–risk with an enlarged spleen were evaluated for eligibility on an individual basis by the sponsor, irrespective of JAK2 mutation status. The starting dose of rux was determined on the basis of baseline platelet count (15 or 20 mg twice daily for pts with platelet counts of 100–200 × 109/L and 〉 200 × 109/L, respectively) and can be adjusted for efficacy and safety. Dose changes during treatment, adverse events (AEs), and serious AEs (SAEs) are registered throughout the program. Results: To date, 1339 requests have been received from 〉 800 physicians in 48 countries, including locations in Europe, Latin America, the Middle East, and Asia. The baseline characteristics are shown in the Table for pts whose requests for access were approved (n = 1240). Drug resupply requests are received every ≈ 3 months. Follow-up information, based on the first resupply request, was available for 381/639 (60%) of the pts who were enrolled in the program prior to February 2012; 303 (80%) remain on rux therapy, 37 (10%) have discontinued, 11 (3%) died, and 30 (8%) did not initiate therapy. Spleen response was available for 247 pts (decreased, n = 201; unchanged, n = 39; increased, n = 7). Changes in constitutional symptoms were available for 203 pts (decreased, n = 151; unchanged, n = 49; increased, n = 3). In pts enrolled in the IPSP undergoing rux treatment, most pts who had a decrease in spleen length also had a decrease in symptoms. Dose-modification information was available for 259 pts, of whom 44 had dose increases and 89 had dose decreases. Reasons for dose modifications included efficacy (n = 28), safety (n = 69), and other reasons (n = 36). Safety information was available for 266 pts; 75 reported significant AEs or SAEs as determined by investigators. Enrolled pt characteristics are generally similar to those expected in the overall MF pt population. Thus far, the proportion of pts enrolled in the IPSP with the JAK2 V617F mutation (73%) is higher than that for the general MF population (50%-60%). This may reflect a misconception that JAK inhibition is primarily effective in pts who have the JAK2 V617F mutation, when in fact rux has demonstrated similar efficacy in both pt types in the phase 1/2 251 study and the two phase 3 COMFORT trials. This may also be reflected in the higher proportion of PPV-MF pts in the IPSP than in the general MF population (28% vs 10%-15%), of whom 95% are JAK2 V617 F–positive. Conclusions: Considerable requests for access to rux have been received through the IPSP, highlighting the need for an effective treatment in pts with a range of IPSS risk-assessment scores. The demographics of the IPSP pts are similar to those expected in the overall MF population. Responses and safety patterns observed in the IPSP appear to be comparable to those from the COMFORT trials. Disclosures: Off Label Use: Jakafi™ (ruxolitinib) is indicated in the United States for the treatment of patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis, post–polycythemia vera myelofibrosis and post–essential thrombocythemia myelofibrosis. In Canada, JAKAVI ® is indicated for the treatment of splenomegaly and/or its associated symptoms in adult patients with primary myelofibrosis (also known as chronic idiopathic myelofibrosis), post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis. This abstract reports on a clinical study conducted outside the US including patients of all risk categories. All patients have provided written informed consent. Zweegman:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Willenbacher:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Raymakers:Novartis: Consultancy. Cantoni:CSL Behring Switzerland: Research Funding; Robapharm/Pierre Fabre Oncology Switzerland: Research Funding; Janssen-Cilag Switzerland: Consultancy; Novartis Oncology Switzerland: Consultancy, Research Funding. Modi:Novartis Pharmaceuticals Corporation: Employment. Khan:Novartis: Employment. Perez:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership. Gisslinger:AOP Orphan Pharmaceuticals AG: Consultancy, Speakers Bureau; Celgene: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Research Funding, Speakers Bureau. Lavie:Novartis: Membership on an entity's Board of Directors or advisory committees. Harrison:Sanofi Aventis: Honoraria; YM Bioscience: Consultancy, Honoraria; Novartis: Honoraria, Research Funding, Speakers Bureau; Shire: Honoraria, Research Funding.

Beschreibung: Abstract 1689 The increase dose of Imatinib, the shift to a Tyrosine Kinase (TKI) inhibitor of second generation or hematopoietic stem cell transplantation are treatment options when there is loss or lack of response to IM in CML; However, in patients without access to these therapeutic alternatives, the use of alkylating drugs or investigational agents is indicated. NF Kappa B pathway is constitutively activated in CML patients therefore the combination of IM with a NF Kappa B inhibitor (as thalidomide) contributes a new very interesting field of research. We treated 21 patients (11 female) with CML Ph +− resistant (n=13) or intolerant (n=8) to IM, mean +− SD age was 44 + 11 years. At diagnosis 16 (79%) were classified as high risk, according with Eutos scale. Mean +− SD time of IM treatment before adding thalidomide (100mg daily) was 47.8 +− 31 months. At the time of this preliminary analysis, mean follow up since thalidomide addition was 5 (1–18 months) and only 13 patients are evaluable for response (Global response rate was 76%): Six had hematological response & Four achieved complete cytogenetic response (CCgR). The first case was a 53 year old female, who started treatment with IM in accelerated phase, was intolerant to IM and neither achieve CCgR with IM, but reached it after 6 months of adding thalidomide and remains with this treatment after 18 months. The second case was a 38 year old female, who achieved CCgR after 6 months within IM treatment, lasted 53 months, and finally thalidomide was added after losing CCgR; she achieved a 2nd CCgR after 7 months with this combination, and continues with thalidomide at 11 months. The third one is a 44 year old female, who only achieved partial CCgR (pCGR), and after indicating thalidomide on accelerated phase, she had CCgR after 4 months of this drug and remains at 6 months of treatment. Finally, the fourth case is a 26 year old female that received thalidomide because of a suboptimal response to IM; she achieved CCgR after 2 months within thalidomide. Eight patients are not evaluable for response yet, but are ongoing and all will be detailed at ASH meeting. Toxicity has been acceptable, mainly grade 1 neurotoxicity & none severe adverse events have been documented. This is the first communication of the use of Thalidomide with Imatinib with promising results which may represent an alternative therapeutic in CML with antiproliferative enhancer and/or synergistic effect in patients with resistance to IM without opportunity of access to other treatments. This cases report open a future very interesting field of research in intolerance and resistance CML. Disclosures: No relevant conflicts of interest to declare.