ALBERT

Description: Introduction: Multiple myeloma (MM) is a patchy bone marrow based malignancy of plasma cells, resulting in painful bone lytic lesions that can be visualized by 18F-FDG-PET-CT. We treated 45 NDMM patients with CRd-R therapy that resulted in high rates of minimal residual disease (MRD) negativity (62%)(Korde et al. JAMA Onc 2015). In this study, we assessed longitudinal FDG response through lenalidomide (Len) maintenance period and aimed to correlate with clinical findings and MRD status. Methods: The details of treatment received, study design and patients' characteristics have already been published. As part of the study design, all patients had serial PET imaging at baseline, after achievement of CR and/or at completion of 8 cycles of CRd, and at year-1 and -2 of Len maintenance, or termination of protocol therapy. Whole body (vertex to toes) static FDG imaging was performed at 1-hour post injection, implemented according to institutional practice. Focal lesions on FGD were defined as: increased uptake (above background reference) within the bone, (excluding articular regions due to high prevalence and likelihood of confounding arthritic disease), maximum standardized uptake value (SUV) 〉1.5 for lesion size on CT ranging from 0.5-1.0 cm, or maximum SUV 〉2.5 for lesions 〉1.0 cm. Results: At baseline, 37/45(82.2%) patients had FDG-positive lesions and 8/45(17.8%) were negative. Median follow-up for longitudinal analysis is 30.1 months. Among initial FDG-negative patients, 7/8 (87.5%) patients remained negative throughout follow-up; 1/8 (12.5%) patients developed a sclerotic FDG-positive lesion deemed not to be progression (rib 5 SUV 1.7). Among the 37 patients with baseline FDG-positive lesions, 12/37(32.4%) patients had complete resolution of FDG-PET-CTs (FDG-responders); 25/37(67.5%) remained FDG-long-term positive at time of last protocol scan. Eight of the 25(32%) FDG-long-term positive patients met IMWG criteria for progression, compared to 0/12 FDG-responders (p value=0.04). For patients with available data, MRD negative status after initial CRd (prior to Len maintenance) was not associated with long-term PET-CT response [19/24(79.2%) vs. 8/11(72.7%), FDG-long-term positive vs. FDG-responders, p=NS]. For the remaining FDG-long-term positive patients not meeting progression criteria, all 17 patients had low-positive persistent FDG with decreased or partial SUV response that decreased over time while on Len maintenance. Conclusions: In patients receiving CRd followed by long-term Len maintenance, 68% of baseline FDG-positive patients have persistent longitudinal FDG-positive myeloma lesions. While there is an increased risk of clinical progression among these patients, the majority showed low-positive FDG lesion uptake that decreased over time with long-term Len maintenance. Long-term resolution of FDG-positive lesions is not associated with MRD status after initial CRd therapy. Further follow-up is needed to examine the significance of persistent FDG-positive lesions in relationship to residual disease and mechanisms of resistance. Figure Figure. Disclosures Korde: Medscape: Honoraria. Hassoun:Takeda: Consultancy, Research Funding; Celgene: Research Funding; Novartis: Consultancy; Binding Site: Research Funding. Landgren:Medscape Myeloma Program: Honoraria; BMS: Honoraria; Merck: Honoraria; Takeda: Honoraria; Amgen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding.

Description: Introduction: BCMA targeted CAR T cell therapy has shown promising results in patients with relapsed/refractory multiple myeloma (MM). Herein, we report on the safety and efficacy of MCARH171, a second generation, human derived BCMA targeted autologous 4-1BB containing CAR T cell therapy, including a truncated epidermal growth factor receptor safety system (Smith EL. Mol Ther 2018). Methods: This is a phase I first in human, dose escalation trial of MCARH171. Patients received conditioning chemotherapy with cyclophosphamide (Cy) 3 gm/m2 as a single dose or fludarabine 30 mg/m2 daily and Cy 300 mg/m2 daily for 3 days followed by MCARH171 infusion in 1-2 divided doses. The trial followed a standard 3+3 design with 4 dose levels where patients received the following mean doses per cohort: (1) 72x106, (2) 137x106, (3) 475x106, (4) 818x106 viable CAR+ T cells. The primary objective was to demonstrate safety, and secondary objectives included efficacy and expansion, and persistence of CAR T cells using PCR from the peripheral blood. The last accrued patient received MCARH171 on Dec 6, 2017 and the data cut-off is July 16, 2018. The study is closed to accrual. Results: 11 patients with relapsed and/or refractory MM were treated. Median number of prior lines of therapy was 6 (range: 4-14), and all patients received prior therapy with a proteasome inhibitor, IMiD, anti-CD38 monoclonal antibody, and high dose melphalan/stem cell transplant. Nine (82%) patients had high-risk cytogenetics and 9 (82%) were refractory to their immediate prior line of treatment. One patient was not evaluable for DLTs given the need for early radiation and steroids for impending spinal cord compression by tumor. There are no DLTs reported. Cytokine release syndrome (CRS) grade 1-2 occurred in 4 patients (40%), grade 3 occurred in 2 (20%), and there was no grade 4-5 CRS. Grade 2 encephalopathy occurred in 1 patient (10%) in the setting of high fevers which resolved in less than 24 hours. There was no grade 3 or higher neurotoxicity observed. Tocilizumab was administered to 3 patients; 2 in cohort 2, and 1 in cohort 3. Laboratory values correlating with CRS reaching grade 3 or requiring Tocilizumab (N=4) compared to those with no or milder CRS (N=6) included peak CRP (mean: 28.5 vs 4.6 mg/dL, p

Description: Background: Several studies have indicated that the depth and duration of treatment response in multiple myeloma are both reduced in the relapsed setting. With further lines of therapy, responses continue to weaken in depth and shorten in duration. The National Comprehensive Cancer Network (NCCN) Guidelines suggest that regimens may be repeated in the relapsed setting if there has been a duration of at least 6 months since that regimen was given; however, there is limited information regarding treatment response and duration in the setting of re-treating patients with agents previously utilized. Moreover, preliminary data has suggested that carfilzomib-based regimens in the frontline may be able to attain deeper and longer responses than alternative therapies, which has led to carfilzomib being used more frequently in the frontline. This motivated us to investigate the treatment response, depth, and safety of re-challenging patients with carfilzomib in the relapsed setting. Methods: In this retrospective chart review, we identified all patients who were treated with multiple courses of carfilzomib-based regimens at Memorial Sloan Kettering Cancer Center between January 1, 2014 and November 30, 2018. Our primary objectives were to assess the response, duration of response and treatment, and safety of re-exposure to carfilzomib-based regimens. Responses were assessed as per IMWG 2016 consensus criteria (Lancet Oncol 2016). In this review we describe the clinical course, safety, and efficacy of re-challenging patients with carfilzomib in the relapsed and refractory settings. Results: Fifteen patients were identified as having received multiple, independent lines of carfilzomib-based therapy. The median age of the cohort was 58 years (49-76) with 53% male (8); two patients had R-ISS stage 1, eight stage 2, and five stage 3 disease. Five of these patients received their initial carfilzomib in the frontline as part of KRD; four of whom attained a sCR with the fifth attaining a VGPR. The remaining ten patients received their initial carfilzomib in the second-line (4) or 3rd and subsequent lines (6). Upon re-exposure to carfilzomib, patients were heavily treated with a median of four lines of therapy (2-15). All but three patients had at least one adverse cytogenetic abnormality; eight with 17p-, five with 13q-, three with t4;14, and six with 1q+. Regimens utilized in the relapsed setting included KRD (N=4), KPD (N=3), Cyklone (N=2), KD + HDAC inhibitor (N=3), KD (N=1), KCD (N=1), and KRD + daratumumab (N=1). Four patients received carfilzomib at a dose of 27 mg/m2 while the remaining 10 received 〉 36 mg/m2. Responses were seen in all but four patients (two VGPR, five PR, and four MR), with one patient experiencing progression during carfilzomib with no response; notably, this patient only attained a MR to primary carfilzomib therapy and their second exposure was the 15th line of therapy. The median time to next therapy was 4.8 months (1.9-19.4) with one patient being bridged to autologous hematopoietic cell transplantation (HCT), one to allogeneic HCT, and three are currently receiving ongoing carfilzomib treatment (13.9, 2.8, 2.5 months with VGPR, MR, and PR, respectively). Exacerbation of baseline hypertension was identified in three patients, but these instances were treated successfully with standard medications with no further complications. No additional cardiovascular events were identified in the frontline or re-treatment settings. Conclusions: We report that in a heavily pre-treated, high risk patient cohort, patients previously treated with carfilzomib-based regimens may be safely re-challenged with carfilzomib. Importantly, none of these patients experienced cardiovascular adverse effects other than exacerbation of underlying hypertension, further supporting the ability to safely re-treat a select group of patients with carfilzomib. We conclude that depending on the patient and treatment history, re-challenging with carfilzomib at relapse may be appropriate salvage therapy, particularly as a bridge towards HCT and/or clinical trials. Disclosures Hassoun: Novartis: Consultancy; Janssen: Research Funding; Celgene: Research Funding. Mailankody:Juno: Research Funding; Celgene: Research Funding; Janssen: Research Funding; Takeda Oncology: Research Funding; CME activity by Physician Education Resource: Honoraria. Lesokhin:Genentech: Research Funding; Serametrix Inc.: Patents & Royalties; Janssen: Research Funding; GenMab: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding; Juno: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Smith:Celgene: Consultancy, Patents & Royalties, Research Funding; Fate Therapeutics and Precision Biosciences: Consultancy. Landau:Prothena: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Caelum: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Honoraria. Shah:Janssen Pharmaceutica: Research Funding; Amgen: Research Funding. Scordo:Angiocrine Bioscience, Inc.: Consultancy; McKinsey & Company: Consultancy. Giralt:Amgen: Consultancy, Research Funding; Spectrum Pharmaceuticals: Consultancy; Miltenyi: Research Funding; Jazz Pharmaceuticals: Consultancy; Actinium: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy; Johnson & Johnson: Consultancy, Research Funding; Kite: Consultancy. Landgren:Karyopharm: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Adaptive: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Theradex: Other: IDMC; Merck: Other: IDMC; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Description: Background Minimal residual disease (MRD) negativity is a strong predictor for outcome in multiple myeloma. Next generation sequencing (NGS) for immunoglobulin heavy chain and kappa light chain VDJ rearrangements has become increasingly more common for MRD assessment. One of the known challenges with NGS for VDJ rearrangements is the vast diversity of sequences that are present, resulting in a need for a multiplex approach as common primers cannot be used to amplify all rearrangements. Also, somatic hypermutation may affect the annealing of primers and decrease the capture rate. The NGS VDJ assay developed by Adaptive Biotechnologies targets all theoretical combinations of VDJ sequences and has been used in several recent large randomized trials in multiple myeloma. The reported ~80% capture rate of the first version of the Sequenta/Adaptive 1.3 assay limited the ability to track MRD status post therapy. The assay has recently been updated and validated to increase resilience to somatic hypermutation. As there is no published reference data using this assay, we were motivated to assess VDJ capture in the clinical setting. Methods In total, 147 patients with newly diagnosed multiple myeloma (NDMM, n=101) or relapse/refractory multiple myeloma (RRMM, n=46) seen at Memorial Sloan Kettering Cancer Center were identified and included in the study. At bone marrow collection, patient samples were sorted for mononuclear cells and a subset of samples were sorted for CD138+ plasma cells. Stored bone marrow samples from these patients underwent DNA extraction and were sequenced with the Adaptive NGS VDJ assay. The same samples were also sequenced for genomic events using our internal NGS panel myTYPE. myTYPE is a custom capture panel targeting the most frequent multiple myeloma associated-somatic mutations, copy number alterations, and IGH translocations. Logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) of detection success in relation to clinical parameters such as age, gender, percent bone marrow plasma cells, as well as immunoglobulin heavy and light chain types, and myTYPE positivity. Results There overall capture rate for a unique VDJ sequence was 80%, 75% in NDMM samples and 89% in RRMM samples, respectively. The VDJ capture rate in samples that were myTYPE positive, e.g. samples with at least one genomic aberration detected by myTYPE, was 94%. In univariate analysis, the ORs of detecting a clonal VDJ sequence was 1.8 (95% CI 1.3-2.5) and 1.5 (1.2-1.9) for every 10% increase in plasma cells on bone marrow aspirate and biopsy, respectively. For every 1g/dL increase in M-spike, the OR of VDJ capture was 1.6 (1.2-2.2). Samples with at least one genomic aberration detected by myTYPE had a significantly higher detection rate of VDJ sequence, the OR of VDJ capture in myTYPE positive samples was 8.8 (3.2-31.3). Conversely, age, gender, type of immunoglobulin heavy chain (IgG or IgA), or light chain type (kappa or lambda) had no significant effect on the VDJ detection rate (Table). In multivariate analysis, myTYPE positivity was found to be an independent predictor of VDJ capture, with an OR of 4.9 (1.6-18.4, p=0.009) for myTYPE positive samples. The ORs were 1.4 (1.1-2.2, p=0.052) for an increase in 10% plasma cells on bone marrow aspirate and 1.5 (0.97-2.3, p=0.083) every 1g/dL increase in M-spike. Conclusion The VDJ capture rate using the updated Adaptive NGS VDJ assay was 94% in multiple myeloma samples of high quality as indicated by myTYPE positivity. The capture success rate was higher in samples with a greater disease burden. As expected, the assay was less sensitive in samples with insufficient DNA content. Our results are supportive of the use of this NGS VDJ in multiple myeloma, but also illustrate the importance of optimal sample ascertainment and processing. Disclosures Jacob: Adaptive Biotechnologies: Employment, Equity Ownership. Korde:Amgen: Research Funding. Mailankody:Juno: Research Funding; Physician Education Resource: Honoraria; Janssen: Research Funding; Takeda: Research Funding. Lesokhin:Serametrix, inc.: Patents & Royalties: Royalties; Squibb: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Janssen: Research Funding; Genentech: Research Funding. Hassoun:Oncopeptides AB: Research Funding. Smith:Celgene: Consultancy, Patents & Royalties: CAR T cell therapies for MM, Research Funding. Landgren:Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy; Amgen: Consultancy, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Consultancy; Merck: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Research Funding.

Description: Abstract 205 Background: Little progress in terms of improving survival in patients with chronic myeloid leukemia (CML) was made until the introduction of interferon alpha and allogeneic stem cell transplantation for selected patients in the 1980s. The management changed dramatically with the development of imatinib mesylate, the first tyrosine kinase inhibitor (TKI) that targets the BCR-ABL1 oncoprotein. In Sweden clinical trials started in December 2000 and the drug was approved for clinical use in November 2001. This study evaluates the impact of treatment developments in CML by studying temporal trends in short-term and long-term excess mortality in a population-based setting. Materials and Methods: Using data from the nationwide, population-based Swedish Cancer Registry and Swedish population life-tables stratified by age, sex, and calendar time we characterized trends in relative survival for all patients diagnosed with CML in Sweden 1973–2008 (n=3,173; 1,796 men and 1,377 women; median age 62 years). Patients were categorized into five age groups (79 years) and five calendar periods (1973-1979, 1980–1986, 1987–1993, 1994–2000 and 2001–2008). Six hundred and nine stem cell transplants (539 allogeneic and 70 autologous) were reported to the EBMT registry during the study period. Results: Incidence remained stable over time with a consistent male predominance. Relative survival improved with calendar period with the greatest improvement in the last two calendar periods (figure). Five-year cumulative relative survival ratios (RSRs; 95% confidence intervals) were 0.21 (0.17-0.24), 0.23 (0.20-0.27), 0.37 (0.33-0.41), 0.54 (0.50-0.58) and 0.80 (0.75-0.83) in the five calendar periods, respectively. Ten-year RSRs were 0.06 (0.04-0.08) and 0.78 (0.73-0.83) in the first and last calendar periods, respectively. This improvement was confined to age groups up to 79 years of age but most pronounced in patients below 60 years. The 5-year RSRs for patients diagnosed 2001–2008 were 0.91 (0.85-0.94), 0.87 (0.78-0.92), 0.82 (0.72-0.90), 0.75 (0.61-0.86), and 0.25 (0.10-0.47) for the five age groups, respectively. Older age at diagnosis and male sex were associated with significantly higher excess mortality rates in models adjusted for potential confounding factors. Conclusion: In this large population-based study including 〉 3,000 CML patients survival increased significantly after 2001 (when imatinib mesylate was approved for clinical use in Sweden) for patients up to 79 years of age. Future studies are needed to assess if very old (〉79 years) CML patients may benefit from an increased use of TKIs. Also newly introduced, targeted treatment options for CML need to be evaluated in future population-based studies. Disclosures: No relevant conflicts of interest to declare.

Description: Background Monoclonal gammopathy of undetermined significance (MGUS) is a precursor condition to multiple myeloma (MM) and other lymphoproliferative disorders. Patients with MM have an increased risk of venous and arterial thrombosis. Results from previous studies have also shown an increased risk of thrombosis in MGUS. However, these studies have been performed on clinically established cohorts, and no previous study has examined the risk of thrombosis in light chain MGUS (LC-MGUS). Methods We performed a population-based study on the longitudinal cohort of the AGES-Reykjavik Study, consisting of 5,764 elderly Icelandic men and women. Through screening all participants with free light chain analysis and serum protein electrophoresis, MGUS and LC-MGUS were identified in 299 and 52 individuals, respectively. The outcome was first incidence/occurrence of venous or arterial thrombosis, as diagnosis or as cause of death. Information on outcomes was supplemented by health care records, available from nine years prior to study baseline and for a median follow-up time of 8.8 years. Through logistic regression, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate history of arterial and venous thrombosis, respectively, at study baseline. A Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% CIs for the risk of first incidence of thrombosis during follow-up. Results A history of any thrombosis during the nine years prior to diagnosis was present in 30 (10.0%) of individuals with MGUS, 13 (25.0%) of individuals with LC-MGUS, and 643 (12.0%) of individuals without MGUS. In a model adjusting for age, sex, smoking, serum cholesterol levels, diabetes, hypertension, and family history of thrombosis, the odds of having had a thrombosis was not significantly different for neither MGUS (OR = 0.75, 95% CI 0.50-1.12) nor LC-MGUS (OR = 1.81, 0.92-3.58), compared to those without MGUS. During a median follow-up time of 8.8 years, 80 (26.8%) of individuals with MGUS, 14 (26.9%) of individuals with LC-MGUS, and 1,344 (25.0%) of individuals without MGUS were diagnosed with thrombosis. Individuals with MGUS and with LC-MGUS had no increased risk of arterial thrombosis, when adjusted for age, sex, cholesterol, diabetes, hypertension, smoking, and family history of thrombosis (HR 1.04, 0.82-1.32). Similarly, no increased risk was found in MGUS or LC-MGUS for venous thrombosis, in a model adjusted for age, sex, body mass index, and previous or current cancer (HR 0.89, 0.41-1.89). Excluding individuals with a diagnosis of thrombosis occurring before baseline, or adjusting for a personal history of thrombosis, did not affect the results. Summary and conclusions In this large, population-based, screening cohort study, we found no increased risk of arterial or venous thrombosis in MGUS. A history of thrombosis was more common in individuals with LC-MGUS, which might be an effect of higher age in LC-MGUS individuals. To our knowledge, this is the first study to investigate risk of thrombosis in LC-MGUS. The results from our screened study contradict previous findings from clinically established cohorts. Future work is needed to better understand observed differences between studies and across populations. For example, potential underlying factors may include aggregation of underlying comorbidities in clinically diagnosed MGUS patients, and biological variations (shared germline genetic susceptibility) by ethnic groups. Table. Risk of thrombosis in individuals with MGUS and LC-MGUS, compared to individuals without MGUS. MGUS LC-MGUS No MGUS No. HR (95% CI) No. HR (95% CI) No. HR (95% CI) Any thrombosis* 80 (26.76%) 1.01 (0.80-1.26) 14 (26.92%) 1.13 (0.80-1.26) 1,344 (25.02%) 1.00 (Reference) Arterial thrombosis† 76 (25.42%) 1.04 (0.82-1.32) 14 (26.92%) 1.16 (0.67-2.01) 1,240 (23.08%) 1.00 (Reference) Venous thrombosis†† 7 (2.34%) 0.89 (0.41-1.89) 0 (0.0%) - 151 (2.81%) 1.00 (Reference) *Results adjusted for age and sex. † Results adjusted for age, sex, smoking, hypertension, cholesterol, diabetes, and family history of arterial thrombosis. †† Results adjusted for age, sex, body mass index, and previous or current cancer. MGUS: monoclonal gammopathy of undetermined significance, LC-MGUS: light-chain monoclonal gammopathy of undetermined significance. HR: hazard ratio, CI: confidence interval. Disclosures Landgren: Celgene: Consultancy; BMJ Publishing: Consultancy; Onyx: Research Funding; International Myeloma Foundation: Research Funding; Bristol-Myers Squibb: Consultancy; Onyx: Honoraria; Celgene: Honoraria; Bristol-Myers Squibb: Honoraria; Medscape: Honoraria; BMJ Publishing: Honoraria; Onyx: Consultancy; Medscape: Consultancy.

Description: Background The Myeloproliferative neoplasms (MPNs) consists of the subtypes polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF), and MPN unclassifiable (MPN-U). The incidence rates of these diseases vary substantially between different reports, ranging from 1.15 to 4.99/100,000 person-years. However, in a recent metaanalysis, there was no significant difference in MPN incidence between Europe and North America and the variations in incidence may therefore reflect the quality of the cancer registers and reporting of MPNs. In addition, there is a limited number of reports on MPN incidence during more recent years. Therefore, we assessed the incidence of MPN based on the Swedish Cancer Register, a high-quality population-based cancer register between 2000 and 2012. Patients and Methods The Swedish Cancer Register was used to identify all patients diagnosed with an MPN between January 1st 2000 and December 31st 2012. These Swedish Cancer Registers have very high levels of quality and completeness. Between 2008 and 2012, the reporting of newly diagnosed MPN to the cancer register was 〉92%. Information on the Swedish population was obtained from the Human Mortality Database (www.mortality.org). Based on information from these registers, incidence rates of MPNs with 95% confidence intervals (CIs) were calculated. Confidence intervals were estimated on the log scale. In addition, the incidence rate in relation to MPN subtype, age group (18-39, 40-49, 50-59, 60-69, 70-79, and ³80 years), as well as calendar year of diagnosis was assessed. Results A total of 5,442 MPN patients were reported to the cancer register between 2000 and 2012. During these years, there were 1,810 incident cases of PV, 1,862 of ET, 636 of PMF, and 1,134 with MPN-U. Between January 1st 2000 and December 31st 2012, the population in Sweden increased from 8,861,426 to 9,555,893 inhabitants. The overall annual incidence rate of MPN was 5.83 (95% CI 5.68-5.99)/100,000 persons. The incidence rate of PV was 1.94 (1.85-2.03), ET 2.00 (1.91-2.09), PMF 0.68 (0.63-0.74), and MPN-U 1.22 (1.15-1.29) per 100,000 person-years. In addition, there was a strong correlation between age and incidence of MPN with incidence rates being substantially higher among the older age groups (Table). The overall incidence rate of MPNs increased during the study period, from 5.06 (4.55-5.62)/100,000 person-years in the year 2000 to 5.98 (5.45-6.55)/100,000 person-years in 2012. The incidence rate of PV was similar throughout the study period, the incidence was 2.05 (1.74-2.42)/100,000 person-years in 2000 and 2.12 (1.81-2.47)/100,000 person-years in 2012. The annual incidence rate of ET and PMF increased, from 1.62 (1.34-1.95) to 2.49 (2.15-2.87) per 100,000 persons for ET and from 0.36 (0.24-0.53) to 0.86 (0.67-1.10) per 100,000 persons for PMF between 2000 and 2012. Conversely, the incidence of MPN-U decreased, 1.03 (0.81-1.29) to 0.52 (0.38-0.71)/100,000 person-years between 2000 and 2012. Summary and Conclusions In this large population-based study, the incidence of MPN was higher than previously reported in both European and North American studies. As earlier lower incidence rates likely are an effect of limited coverage of cancer registers, there may be an underreporting of MPNs in many European and American countries. The increase in MPN incidence rates during the study period may reflect increasing life expectancy of the Swedish population, improved reporting to the cancer register as well as changes in the classification and diagnostic systems. Similarly, the decrease in incidence of MPN-U is also likely a result of improved diagnostics during more recent years. In conclusion, the MPN incidences rates reported here are presumably more accurate compared to earlier reports due to the high level of coverage and accuracy of the Swedish registers. Table 1. Incidence rates of MPNs overall and in relation to subtype and age at diagnosis Total number MPN diagnosed 2000-2012 Incidence/100 000 person-years (95% confidence interval) All MPN 5,442 5.83 (5.68-5.99) Subtype PV 1,810 1.94 (1.85-2.03) ET 1,862 2.00 (1.91-2.09) PMF 636 0.68 (0.63-0.74) MPN-U 1,134 1.22 (1.15-1.29) Age at diagnosis (years) 18-39 226 0.67 (0.59-0.76) 40-49 361 2.26 (2.04-2.51) 50-59 769 4.92 (4.58-5.28) 60-69 1,228 9.54 (9.02-10.1) 70-79 1,680 18.99 (18.1-19.9) 〉80 1,178 18.92 (17.87-20.03) Disclosures Landgren: BMJ Publishing: Honoraria; Bristol-Myers Squibb: Honoraria; Medscape: Honoraria; Onyx: Honoraria; Celgene: Honoraria; International Myeloma Foundation: Research Funding; Medscape: Consultancy; BMJ Publishing: Consultancy; Onyx: Research Funding; Bristol-Myers Squibb: Consultancy; Onyx: Consultancy; Celgene: Consultancy.

Description: Abstract 3071 Background: Available data on survival patterns among patients diagnosed with myeloproliferative neoplasms (MPN) show a great diversity. For instance, in essential thrombocythemia (ET) there are reports stating that survival is not affected by the disease while other investigators consider ET to be a serious disease that significantly reduces life expectancy. Patients with primary myelofibrosis (PMF) are consistently reported to have a shortened life span while polycythemia vera (PV) is associated with a reduced survival in many, but not all, studies. We conducted a comprehensive, population-based study to assess survival and to define causes of death MPN patients, and to compare patterns to the general population. Patients and Methods: The nationwide Swedish Cancer Registry was used to identify all cases of MPN between 1973 and 2008 with follow-up to 2009. Relative survival ratios (RSRs) and excess mortality rate ratios (EMRRs) were computed as measures of survival. The Cause of Death Registry was used to obtain information on causes of death both in the patient and the general population. Results: A total of 9,384 MPN patients were identified (PV n=4,389, ET n=2,559, PMF n=1,048 and MPN not otherwise specified (MPN NOS) n=1,288); 47% were males and the median age at diagnosis was 71. The reporting rate to the Cancer Registry increased over time being well above 95% during the most recent calendar period. There was a significant overall excess mortality in all subtypes of MPN, reflected in 5-year and 10-year RSRs of 0.83 (95% CI 0.81–0.84) and 0.64 (0.62-0.67) for PV, 0.80 (0.78-0.82) and 0.68 (0.64-0.71) for ET and 0.39 (0.35-0.43) and 0.21 (0.18-0.25) for PMF, respectively. Higher age at MPN diagnosis was associated with a poorer survival. For example, the 10-year RSR for patients

Description: Introduction The complete blood count is one of the most frequently ordered patient blood test. It provides the most basic hematological measurements including hematocrit (Hct), white blood cell count (WBC), and platelet count (PLT). An increase in some of these markers have been shown to be associated an increased thrombotic risk. Most notablyHctfor patients with polycythemiaveraand WBC and PLT in cancer patients. Some population studies have shown an increased propensity of thrombosis among healthy individuals with elevatedHct. However these studies have not included sufficient clinical data to account for potential confounders. The aim of this study is to assess whether elevation of these hematological markers are risk factors for thrombosis in the general population. Methods Complete blood count and baseline characteristics were obtained from participants in the Reykjavik-AGES study at enrollment in 2002. The Reykjavik-AGES study, a nationwide screening study of 5755 elderly individuals, includes thorough medical history, physical examination, and blood measurements. Lifetime incidents of thrombotic events were recorded up to 2015 in the Icelandic National Health Service and cross-linked to the participants of the study through the National Registry of the total Population. Primary outcomes of arterial and venous thrombosis were considered separately 10 years before and after enrollment. Hct, WBC, and PLT were used to determine exposure and stratified into five quintiles in four respective analyses. The second quintile was used as a reference group. Cox proportional hazard regression was used to determine hazard ratios and confidence intervals. We then adjusted for age, gender, body mass index, diabetes mellitus, cigarette smoking (in pack years), hypertension and statin use. For arterial thrombosis we also adjusted for family history of arterial thrombosis and for venous thrombosis we censored at diagnosis of malignant neoplasm. In the analysis of WBC we also adjusted for C-reactive protein, an acute phase protein. Individuals with abnormal values of these parameters were excluded from the study (PLT 〈 150x109/L, WBC 〉 13x109/L or 〈 2.0,Hct 〈 35% were excluded) Results Crude analyses ofHctrevealed a dose dependent increased risk of arterial (hazard ratio (HR) 1.2, 95% confidence interval (CI) 1.08-1.33, p