ALBERT

Description: 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.

Description: Abstract 3881 Poster Board III-817 Background For MM patients with malignant bone lesions (BM), SREs including pathologic fracture, spinal cord compression, hypercalcemia of malignancy, and radiotherapy and/or surgery to bone are associated with significant morbidity and mortality and reduced quality of life. ZOL is an IV bisphosphonate (BP) proven to reduce and delay incidence of SREs in several tumor types. This study was designed to assess the benefit of long-term ZOL use in a real-life setting. Methods Claims-based analysis of commercial and Medicare data from a large US managed care plan and a 45 health-plan database was used to evaluate SRE rates, time from BM to 1st SRE, and mortality in patients treated with ZOL or no IV BP therapy. Patients older than 18 years with MM and BM diagnosed between Jan 2001 and Dec 2006 were included. Treatment Persistency was defined as the absence of a 〉45 day gap between ZOL administrations. Continuous enrollment in the health plan for 6 months before and no prior evidence of BM or IV BP use were required. When assessing mortality, patients with a date of death less than 30 days following index date were excluded. Patients were followed until they disenrolled from the plan or to the end of the study's follow-up period. In this study, SREs were defined as evidence of pathologic fracture, spinal cord compression, and radiotherapy and/or surgery to bone. Results The study sample included 1,655 Patients with a mean age of 61.7 ± 11.9 years; approx. 64% were treated with ZOL and 36% with no IV BP. Incidences of SREs and mortality rates were both greater in the no IV BP group (incidence rate ratio [IRR] = 1.58; p-value

Description: Abstract 4944 Background MM patients with BM may be treated with a variety of anti-cancer and bone treatments. The purpose of this study was to examine the use of ZOL, a therapy administered intravenously to reduce or delay skeletal complications, in the real-world treatment of adult patients with MM and BM. Of special interest to the study was the use of ZOL in the context of bortezomib (BOR) and lenalidomide (LEN). Methods Claims-based analysis of commercial and Medicare data from a large US managed care plan and a 45-health plan database was conducted to examine the use of ZOL in the treatment of adult patients (18 years and older) with MM and BM. Patients with at least one claim for ZOL and evidence of MM diagnosis and BM diagnosis were included. The identification period was 7/1/03 – 7/31/08 for the large US commercial health plan, 7/1/03 – 12/31/07 for the Medicare plan, and 7/1/04 – 6/30/08 for the 45-health plan database. The sequencing, number, and duration of ZOL treatments were analyzed. Continuous enrollment in the health plan for six months before and three months following the index date was required. Patients were followed until they disenrolled from the plan (including due to death), or the end of the study's follow-up period. Results The study sample included 8,632 of which 4,260 patients were enrolled in their health plan for at least one year following ZOL initiation, with a median follow-up length of 21.2 months (range = 12 months to 5.3 years). Among the 4,260 patients, 38.7% were men, the mean age was 60.7 ± 11.9 years, and the average Charlson comorbidity index score was 5.4 (SD=2.2). Accounting for variable follow-up during the study period, patients had an average of 7.01 ZOL administrations per person year. Approximately 63.5% (n=2,707) patients were still receiving ZOL at the end of the first year following ZOL initiation. The majority of patients (90.2%, n=3,841) treated with ZOL were not treated with either BOR or LEN. Approximately 93.0% of these cases received other types of anti-cancer treatments (e.g., melphalan, thalidomide, prednisone, and other chemotherapies) at some point during the study period. For 345 (8.1%) patients, BOR or LEN initiation followed the start of ZOL, and 185 (53.6%) of these cases started BOR or LEN within the first year following initiation of ZOL. Among those initiating BOR or LEN, the median time from ZOL initiation was 337 days (range = 5 to 1,594 days). In 19 (0.4%) cases, ZOL was started at the same time as BOR or LEN, and in 55 (1.3%) cases, ZOL treatment followed BOR or LEN initiation. Conclusions According to this retrospective database analysis, the vast majority of patients with MM and BM who initiate ZOL do not go on to receive BOR or LEN within the year following ZOL initiation. Among patients enrolled in the health plan for at least one year following ZOL initiation, the majority of patients remained on ZOL treatment. As anticipated, this study showed that the overwhelming proportion of MM patients with BM using ZOL were being treated with anti-cancer therapies, but only approximately 10.0% with either BOR or LEN. Disclosures Kaura: Novartis: Employment, Equity Ownership. Perez:Novartis: Employment, Equity Ownership.

Description: Abstract 5170 Background: There are currently no approved, effective drug therapies for myelofibrosis (MF). Ruxolitinib (INC424), a potent and selective oral JAK1 and JAK2 inhibitor, has recently demonstrated rapid and durable reductions in splenomegaly and improved disease-related symptoms, role functioning, and quality of life in 2 phase 3 studies in patients with MF. Both studies met their primary endpoint of the proportion of patients with ≥35% reduction in spleen volume at 24 weeks (COMFORT-I) and at 48 weeks (COMFORT-II): 41.9% vs 0.7% (ruxolitinib vs placebo, P