scholarly journals Clinical Characteristics and Treatment Patterns By Risk Stratification in Patients with Essential Thrombocythemia: An Analysis of the MOST Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 12-13
Author(s):  
Michael R. Grunwald ◽  
Ivy Altomare ◽  
Robyn M. Scherber ◽  
Patricia Kalafut ◽  
Haobo Ren ◽  
...  
Keyword(s):  
High Risk ◽  
Observational Study ◽  
Essential Thrombocythemia ◽  
Research Funding ◽  
Clinical Characteristics ◽  
Symptom Burden ◽  
Low Risk ◽  
Publicly Traded ◽  
Real World Data ◽  
Patient Reported

Background: Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm (MPN) characterized by thrombocytosis and increased risk of thrombotic events and hemorrhage. Treatment of ET is risk-adapted, focused on preventing thrombosis, bleeding, and minimizing symptoms. Real-world data regarding factors contributing to treatment initiation and therapy choice in this setting are limited. Here, we present the clinical characteristics of low- and high-risk pts with ET enrolled in Myelofibrosis and Essential Thrombocythemia Observational STudy (MOST) and assess whether these differ for pts who were treated vs untreated at the time of enrollment. Methods: MOST (NCT02953704) is an ongoing multicenter, non-interventional, longitudinal, prospective, observational study in pts with specific risk categories of ET or MF. Pts included in this analysis met modified ELN criteria (J Clin Oncol. 2011;29:761) for high-risk ET (age ≥60 y and/or thromboembolic event [TE] history) or low-risk ET if receiving ET-directed therapy (not including aspirin only). Data from pt records were entered into an electronic case report form during usual-care visits over a planned observation period of 36 months. Patient-reported symptom burden was assessed using the MPN-Symptom Assessment Form (MPN-SAF); Total Symptom Score (TSS) was calculated (0 [absent] to 100 [worst imaginable]; J Clin Oncol. 2012;30:4098). Data were analyzed with basic descriptive and inferential statistics. Results: Of 1235 pts with ET enrolled at 124 sites between 11/29/2016 and 12/31/2018, 1210 were included in the analysis; 25 were excluded (low-risk receiving aspirin alone [n=16]; low risk receiving neither ET-directed therapy nor aspirin [n=8]; BCR-ABL mutation-positive [n=1]). Of the 1210 pts analyzed, 159 (13.1%) were low-risk (all treated), 887 (73.3%) were high-risk and treated, and 164 (13.6%) were high-risk and untreated, respectively. Reasons for high-risk categorization were similar for treated and untreated high-risk pts (age ≥60 y, 67.5% vs 70.1%; TE history, 8.8% vs 10.4%; both age ≥60 y and TE history, 23.7% vs 19.5%). Pt characteristics are listed in Table 1A. Compared with low risk pts, significantly more high risk pts were JAK2 V617F positive (P = 0.0143); fewer were CALR positive, and more were MPL positive. Pts with high-risk disease who were untreated had the highest proportion of palpable splenomegaly; mean palpable spleen length below the costal margin was greater in treated pts (low- and high-risk) than in untreated pts. Blood counts were similar across cohorts, except platelets were elevated for untreated high-risk pts. The proportion of pts with comorbidities was similar across cohorts; cardiovascular comorbidities were not as common among low- vs high-risk pts. Mean TSS was highest for low-risk pts, and was similar in both treated and untreated high-risk pts. Fatigue was the most severe symptom in all cohorts. Mean MPN-SAF TSS was significantly higher for low- vs high risk pts (P = 0.0007), as were several individual symptom scores (abdominal discomfort, P = 0.0081; concentration, P = 0.0014; numbness/tingling, P = 0.0361; night sweats, P < 0.0001; itching, P = 0.0131; bone pain, P = 0.0206; weight loss, P = 0.0469). Physician-reported signs and symptoms were generally more common in low- vs high-risk pts, with differences between risk groups reaching significance for headache (P = 0.0009) and abdominal pain (P = 0.0455). Among currently untreated high-risk pts, 40.9% had not received any previous ET-directed therapy. Hydroxyurea (HU) was the most common ET-directed monotherapy at enrollment in both low- and high-risk treated pts (Table 1B). A small proportion of pts in both low- and high-risk treated groups was receiving >1 ET-directed therapy. Conclusion: These real-world data from the MOST study indicate that despite treatment, low-risk pts had greater patient-reported symptom burden and physician-reported signs/symptoms than high-risk (treated or untreated) pts. This finding suggests that current management (most commonly with HU in this analysis) may not address symptoms in low-risk pts. Notably, nearly 60% of currently untreated high-risk pts had been previously treated, highlighting an unmet need for effective and tolerable second-line treatments in pts with high-risk ET. Further analyses from MOST will help define changes in the clinical and treatment characteristics of pts with ET over time. Disclosures Grunwald: Premier: Consultancy; Janssen: Research Funding; Amgen: Consultancy; Celgene: Consultancy; Merck: Research Funding; Genentech/Roche: Research Funding; Amgen: Consultancy; Celgene: Consultancy; Pfizer: Consultancy; Trovagene: Consultancy; Premier: Consultancy; Astellas: Consultancy; Astellas: Consultancy; Premier: Consultancy; Forma Therapeutics: Research Funding; Cardinal Health: Consultancy; Merck: Consultancy; Merck: Consultancy; Forma Therapeutics: Research Funding; Forma Therapeutics: Research Funding; Janssen: Research Funding; Abbvie: Consultancy; Incyte: Consultancy, Research Funding; Genentech/Roche: Research Funding; Amgen: Consultancy; Abbvie: Consultancy; Agios: Consultancy; Cardinal Health: Consultancy; Pfizer: Consultancy; Daiichi Sankyo: Consultancy; Agios: Consultancy; Astellas: Consultancy; Daiichi Sankyo: Consultancy; Trovagene: Consultancy; Genentech/Roche: Research Funding; Incyte: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Celgene: Consultancy; Pfizer: Consultancy; Cardinal Health: Consultancy; Agios: Consultancy; Merck: Consultancy; Daiichi Sankyo: Consultancy; Trovagene: Consultancy; Abbvie: Consultancy. Altomare:Bayer: Consultancy; Rigel: Consultancy; Amgen: Consultancy; Incyte: Consultancy, Research Funding; Novartis: Consultancy. Scherber:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Kalafut:Incyte: Current Employment, Current equity holder in publicly-traded company. Ren:Incyte: Current Employment, Current equity holder in publicly-traded company. Verstovsek:Blueprint Medicines Corp: Research Funding; Roche: Research Funding; NS Pharma: Research Funding; Celgene: Consultancy, Research Funding; ItalPharma: Research Funding; Gilead: Research Funding; CTI Biopharma Corp: Research Funding; Genentech: Research Funding; Novartis: Consultancy, Research Funding; Sierra Oncology: Consultancy, Research Funding; PharmaEssentia: Research Funding; AstraZeneca: Research Funding; Protagonist Therapeutics: Research Funding; Promedior: Research Funding; Incyte Corporation: Consultancy, Research Funding.

scholarly journals To Treat or Not to Treat? Understanding Treatment Patterns in Patients with Lower-Risk Myelofibrosis at the Time of Enrollment in the MOST Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 49-51
Author(s):  
Rami S. Komrokji ◽  
Brady L. Stein ◽  
Robyn M. Scherber ◽  
Patricia Kalafut ◽  
Haobo Ren ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Lower Risk ◽  
Research Funding ◽  
Symptom Burden ◽  
Risk Groups ◽  
Treatment Patterns ◽  
Low Risk ◽  
Publicly Traded ◽  
Advisory Committees ◽  
Therapy Initiation

Background: Myelofibrosis (MF) is a chronic Philadelphia chromosome-negative myeloproliferative neoplasm (MPN) characterized by extramedullary hematopoiesis, bone marrow fibrosis, splenomegaly, constitutional symptoms, and diminished quality of life. Treatment decisions may involve a variety of factors including prognosis and symptomatology. Data regarding real-world disease and demographic factors that contribute to therapy initiation and choice in pts with lower risk MF are limited. This analysis of data from the ongoing Myelofibrosis and Essential Thrombocythemia Observational STudy (MOST; NCT02953704) assessed whether these factors differ for lower risk pts who were treated vs untreated at enrollment. Methods: MOST is a longitudinal, noninterventional, prospective, observational study in pts with MF or essential thrombocythemia enrolled at clinical practices within the US. Pts included in the analysis (≥18 y), had low risk MF by the Dynamic International Prognostic Scoring System (DIPSS; Blood. 2010;115:1703), or intermediate-1 (INT-1) risk by age >65 y alone. Pt data were entered into an electronic case report form during usual-care visits over a planned 36-month observation period. Pt-reported symptom burden was assessed using the MPN-Symptom Assessment Form (MPN-SAF); Total Symptom Score (TSS) was calculated (0 [absent] to 100 [worst imaginable]; J Clin Oncol. 2012;30:4098). Data were analyzed with basic descriptive and inferential statistics. Results: Of 233 pts with MF enrolled at 124 sites between 11/29/2016 and 03/29/2019, 205 were included in this analysis; 28 were excluded for being INT-1 risk for reasons other than age. Of the 205 pts, 85 (41.5%) were low- and 120 (58.5%) were INT-1 risk; 56.5% (48/85) and 59.2% (71/120), respectively, were being treated at enrollment. Pt characteristics are listed in Table 1A. Fewer low- vs INT-1 risk pts were JAK2 V617F or MPL positive, and more were CALR positive. The proportion of pts with palpable splenomegaly was similar for treated low- and INT-1 risk pts. In low risk pts, the proportion of pts with palpable splenomegaly was higher in untreated vs treated pts; whereas, in INT-1 risk pts, the opposite was observed (ie, lower proportion in untreated vs treated pts). Blood counts were generally similar across cohorts, except median leukocytes were lower for low risk treated pts and platelet counts were elevated in low- vs INT-1 risk pts. The proportion of pts with comorbidities was similar across cohorts, except for fewer cardiovascular comorbidities in low- vs INT-1 risk pts. Mean TSS was lower in low- vs INT-1 risk pts, but the proportion of pts with TSS ≥20 was greater in treated vs untreated pts in both low- and INT-1 risk groups. Fatigue was the most severe pt-reported symptom in all cohorts. Differences in mean TSS and individual symptom scores between risk groups were not significant (P > 0.05), except itching was worse among INT-1 risk pts (P=0.03). Physician-reported signs and symptoms were generally more frequent for untreated vs treated pts, irrespective of risk (all P > 0.05). Most low risk (69.4%) and INT-1 risk pts (61.2%) who were currently untreated at enrollment had not received any prior MF-directed treatment (Table 1B); the most common prior treatment among currently untreated pts was hydroxyurea (HU) in both risk groups. Of currently treated pts, HU was the most common MF-directed monotherapy at enrollment in low-risk pts, and ruxolitinib was most common in INT-1 risk pts. No low risk pts and few INT-1 risk pts were currently receiving >1 MF-directed therapy at enrollment. Conclusion: These real-world data from pts with MF enrolled in MOST show that a substantial proportion of both low- and INT-1 risk pts who had received treatment before enrollment were not being treated at the time of enrollment. Although watch-and-wait is a therapeutic option, the finding that many of these lower risk pts had in fact received prior therapies suggests an unmet need for effective and tolerable second-line treatment options. Treated pts had greater pt-reported symptom burden vs untreated pts, which suggests that high symptom burden may contribute to the decision for treatment. Prospective studies are needed to evaluate symptom burden change with therapy initiation. In this regard, future analyses of data from MOST are planned to assess the longitudinal evolution of the clinical characteristics, treatment patterns, and management of pts with MF. Disclosures Komrokji: Geron: Honoraria; Agios: Honoraria, Speakers Bureau; AbbVie: Honoraria; Incyte: Honoraria; Novartis: Honoraria; BMS: Honoraria, Speakers Bureau; JAZZ: Honoraria, Speakers Bureau; Acceleron: Honoraria. Stein:Incyte: Research Funding; Kartos: Other: educational content presented; Constellation Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Pharmaessentia: Membership on an entity's Board of Directors or advisory committees. Scherber:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Kalafut:Incyte: Current Employment, Current equity holder in publicly-traded company. Ren:Incyte: Current Employment, Current equity holder in publicly-traded company. Verstovsek:Incyte Corporation: Consultancy, Research Funding; Roche: Research Funding; Genentech: Research Funding; Blueprint Medicines Corp: Research Funding; CTI Biopharma Corp: Research Funding; NS Pharma: Research Funding; ItalPharma: Research Funding; Celgene: Consultancy, Research Funding; Gilead: Research Funding; Protagonist Therapeutics: Research Funding; Novartis: Consultancy, Research Funding; Sierra Oncology: Consultancy, Research Funding; PharmaEssentia: Research Funding; AstraZeneca: Research Funding; Promedior: Research Funding.

scholarly journals Hydroxyurea Treatment History and Quality of Life in Patients with Polycythemia Vera: Results from the MPN Landmark Survey in the United States

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4077-4077
Author(s):  
Ruben A. Mesa ◽  
Carole B. Miller ◽  
John O. Mascarenhas ◽  
Maureen Thyne ◽  
Sara Goldberger ◽  
...  
Keyword(s):  
High Risk ◽  
Research Funding ◽  
Symptom Burden ◽  
Employment Equity ◽  
Treatment History ◽  
The Past ◽  
Patient Reported ◽  
The Us ◽  
Equity Ownership

Abstract Background: Patients with the myeloproliferative neoplasm (MPN) polycythemia vera (PV) require treatment to manage blood cell counts and reduce the risks of cardiovascular/thromboembolic events. Hydroxyurea (HU) is a common cytoreductive treatment; however, some patients discontinue HU treatment because of resistance, intolerance, or frequently a combination of both limitations. Patients may also continue to receive HU despite diminishing or nonexistent clinical benefit, sometimes in combination with persistent need for phlebotomy procedures. This analysis of MPN Landmark survey data examined patient-reported quality of life (QoL) outcomes in patients with PV who were naive to HU (HU-N), were continuing HU (HU-C), or had discontinued HU (HU-D). Methods: Patients with an MPN under active management in the US were eligible to complete an online survey (fielded May - July 2014). This is a report of responses given by patients with PV to questions about symptom burden, QoL, activities of daily living (ADL), and work/productivity. PV-related effects on patients feeling depressed/discouraged, patients feeling anxious/worried, or interference with ADLs were considered to be at high levels if the patient-reported score was ≥4 on a scale of 1 (not at all) to 5 (a great deal). Symptom severity was rated on a scale of 0 (absent) to 10 (worst imaginable). Results: The survey respondents included 380 patients with PV (HU-N, n=159; HU-C, n=181; HU-D, n=40). Mean age was 62.2 years, 65.1 years, and 64.2 years in the HU-N, HU-C, and HU-D groups, respectively. Mean duration of PV was 8.3 years, 10.3 years, and 13.9 years in the HU-N, HU-C, and HU-D groups, respectively. Patients who had not received HU were currently or previously treated with phlebotomy (87.4%), interferon (11.3%), or anagrelide (9.4%); 66.0% of HU-N patients were classified as high-risk based on information provided by the patients in the survey (ie, age 60 or older or history of thrombosis). Among HU-C and HU-D patients, treatment history included phlebotomy (89.5% and 100%, respectively), interferon (7.2% and 52.5%), or anagrelide (15.5% and 35.0%); 79.6% and 82.5%, respectively, were classified as high-risk. Ruxolitinib was not FDA-approved for PV at the time of this survey. Patients reported high levels of feeling anxious/worried and depressed/discouraged as a result of their PV across all subgroups: HU-N, 27.7% and 15.1%, respectively; HU-C, 22.7% and 15.5%; HU-D, 32.5% and 22.5%. Many patients also experienced a high level of PV-related interference with ADLs, which was more common in the HU-D group (30.0%) than the HU-N (11.3%) or HU-C (18.2%) groups. HU-D patients were more likely to have reported ever reducing their work hours (54.2% of the patients who responded) compared with the HU-N (33.3%) and HU-C groups (36.8%). Among all patients, HU-D patients reported a mean of 8.3 doctor visits in the past 12 months, compared with 5.6 in the HU-N group and 6.6 in the HU-C group. Most patients had experienced PV-related symptoms in the past 12 months (Table 1), particularly fatigue, itching, and day/night sweats; fatigue was ranked first as the symptom that patients would most like to resolve. Conclusion: Patients with PV in a large retrospective real-world survey across the US are found to experience burdensome PV-related symptoms and reduced QoL. The findings from this study also show that standard treatments do not address these aspects of PV in many patients, and patients who have discontinued HU may experience an even greater disease burden, possibly because of a lack of effective and/or safe alternative treatment options. Importantly, while 66.0% of the patients in the HU-N group were classified as high-risk, the majority of the high-risk patients in the HU-N group (81.0%) were not treated with cytoreductive agents, suggesting a potential knowledge deficit regarding recommendations for PV management. Collectively, these results illustrate the adverse impact of PV-related symptom burden on patient QoL and reinforce the importance of unmet control of PV-related symptoms in choosing PV therapy. Disclosures Mesa: Novartis Pharmaceuticals Corporation: Consultancy; NS Pharma: Research Funding; Pfizer: Research Funding; Genentech: Research Funding; CTI Biopharma: Research Funding; Incyte Corporation: Research Funding; Promedior: Research Funding; Gilead: Research Funding. Miller:Incyte Corporation: Honoraria, Research Funding. Mascarenhas:Promedior: Research Funding; Roche: Research Funding; CTI Biopharma: Research Funding; Incyte Corporation: Research Funding; Novartis Pharmaceuticals Corporation: Research Funding; Kalobios: Research Funding. Thyne:Incyte Corporation: Speakers Bureau. Paranagama:Incyte Corporation: Employment, Equity Ownership. Parasuraman:Incyte Corporation: Employment, Equity Ownership. Fazal:Bristol Myers Squibb: Consultancy, Honoraria, Speakers Bureau; Ariad: Consultancy, Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau. Naim:Incyte Corporation: Employment, Equity Ownership. Mangan:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Patient Experiences with Liposomal Daunorubicin and Cytarabine (CPX-351) Versus Conventional Induction Regimens: An Analysis of Patient-Reported Outcomes Data from a Prospective Trial

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 29-30
Author(s):  
Thomas W. Leblanc ◽  
Susan Morris ◽  
Michael Hooks ◽  
Susan C. Locke ◽  
Areej El-Jawahri
Keyword(s):  
Patient Experience ◽  
Research Funding ◽  
Symptom Burden ◽  
Exploratory Analysis ◽  
Depression Symptoms ◽  
Publicly Traded ◽  
Patient Reported ◽  
Ptsd Checklist ◽  
Clinically Significant

Background: CPX-351 (Vyxeos®; daunorubicin and cytarabine liposome for injection) is a treatment for adults with newly diagnosed AML with myelodysplasia-related changes or therapy-related AML. Intensive induction chemotherapy causes marked symptom burden, quality of life (QOL) impairment, and psychological distress, but data on the patient experience with CPX-351 are lacking. We aimed to compare the patient experience of physician-chosen CPX-351 to standard induction regimens using validated patient-reported outcome (PRO) measures collected prospectively in a randomized clinical trial. Methods: This was an exploratory analysis of a US, multi-site supportive care trial in AML (NCT02975869). PRO assessments were collected at baseline, 2 weeks later (when studies show patients feel their worst during a typical induction hospitalization), and then at 1, 3, and 6 months. PROs assessed the following patient experience domains: symptoms (Edmonton Symptom Assessment Scale [ESAS]), QOL (FACT-Leukemia and FACT-TOI), anxiety (HADS-A), depression (HADS-D), and post-traumatic stress (PTSD Checklist). All analyses were adjusted for baseline PROs, patient age, receipt of additional targeted therapy, and supportive care interventions. Analysis of covariance models were used to find adjusted 2-week PRO scores by treatment, and logistic regression models were used to find adjusted odds ratios (aOR) for dichotomous PROs at 2 weeks. Linear mixed effects models were used to estimate adjusted mean between-group differences in PROs across the 6-month study period (reported as B). Given the exploratory nature of this study, we defined a 2-sided P value of <0.20 as hypothesis-generating, consistent with standard approaches to exploratory analysis, and not to imply significance. Results: Across 4 sites, we enrolled 109 patients with newly diagnosed AML. Thirty-five (32%) received CPX-351 and 74 (68%) received a standard regimen (72 received 7+3, 1 received FLAG, and 1 received MEC). Baseline sociodemographic characteristics and PROs were similar across groups. Mean age was 67 years (SD: 6.8) in the CPX-351 group and 65.2 (SD: 8.9) in the standard group. Most patients were white (>90%) and partnered (>70%). At 2 weeks, those receiving CPX-351 had better PRO scores (adjusted means) for symptoms (ESAS total score: 25.89 vs 31.73; P = 0.11) and depression (HADS-D: 5.17 vs 7.0; P = 0.08); CPX-351 was favored on all other PROs, including quality of life (FACT-Leu: 118.02 vs 112.56; P = 0.44), anxiety (HADS-A: 4.51 vs 5.27; P = 0.465), and PTSD symptoms (PTSD-checklist: 27.08 vs 28.16; P = 0.6). At 2 weeks, patients receiving CPX-351 were less likely to have worsening ESAS total symptoms (45.7% vs 54.1%; aOR = 0.52; P = 0.172), physical symptoms (45.7% vs 63.5%; aOR = 0.41; P = 0.064), and clinically significant depression symptoms (27.3% vs 37.7%; aOR = 0.48; P = 0.159), but no difference in clinically significant anxiety symptoms (28.9% vs 30.3%; aOR = 0.62; P = 0.392). In longitudinal analyses, those receiving CPX-351 had better QOL (FACT-TOI: B = 6.41; P = 0.173), lower anxiety (B = −1.47; P = 0.153), less depression symptoms (B = −1.58; P = 0.09), and less leukemia symptoms (B = 3.67; P = 0.16), but no differences in total symptom burden (ESAS: B = −0.06; P = 0.988) or in PTSD symptoms (PTSD Checklist: B = 2.23; P = 0.354). While patients receiving CPX-351 had a longer index hospitalization length of stay compared to standard induction (mean of 44.3 vs 39 days; P = 0.072), they also had fewer hospitalizations during the 6-month follow-up period (2.82 vs 3.55; P = 0.158). Furthermore, the total number of days hospitalized after the index admission was lower for those receiving CPX-351 (17.71 vs 22.27 days; P = 0.199). Patients receiving CPX-351 had an average of 94.08 days alive and out of the hospital, while those receiving standard induction had 91.85 days (P = 0.849). Conclusions: This exploratory analysis supports the observation that patients receiving CPX-351 may have an overall better patient experience during induction treatment, as measured by validated PROs assessing symptoms, QOL, mood, and PTSD. Our ability to draw more definitive conclusions is limited by sample size and the fact that treatment with CPX-351 is only indicated for certain AML subtypes, resulting in a non-random allocation to treatment groups and potential differences in clinical outcomes. Disclosures Leblanc: AstraZeneca: Research Funding; Agios, AbbVie, and Bristol Myers Squibb/Celgene: Speakers Bureau; UpToDate: Patents & Royalties: Royalties; American Cancer Society, BMS, Duke University, NINR/NIH, Jazz Pharmaceuticals, Seattle Genetics: Research Funding; AbbVie, Agios, Amgen, AstraZeneca, CareVive, BMS/Celgene, Daiichi-Sankyo, Flatiron, Helsinn, Heron, Otsuka, Medtronic, Pfizer, Seattle Genetics, Welvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Morris:Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Hooks:Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. El-Jawahri:Jazz Pharmaceuticals: Research Funding.

scholarly journals Disease and Clinical Characteristics of Patients with Essential Thrombocythemia Enrolled in the MOST Study

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4306-4306
Author(s):  
Abdulraheem Yacoub ◽  
Roger M. Lyons ◽  
Srdan Verstovsek ◽  
Ryan Shao ◽  
David Tin Chu ◽  
...  
Keyword(s):  
United States ◽  
Observational Study ◽  
Board Of Directors ◽  
Essential Thrombocythemia ◽  
Research Funding ◽  
Clinical Characteristics ◽  
The United States ◽  
Advisory Committees ◽  
History Of ◽  
Equity Ownership

Abstract Introduction: Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm characterized by clonal platelet production and an increased risk for thrombotic and hemorrhagic events. Limited real-world data exist regarding the clinical characteristics and treatment patterns of ET in the United States; most prior data have been generated outside the United States. The Myelofibrosis and Essential Thrombocythemia Observational STudy (MOST) is an ongoing observational study being conducted to describe contemporary demographics, burden of disease, clinical management, and patient-reported outcomes in patients with specific risk categories of myelofibrosis (MF) or ET in the United States. This analysis describes the clinical characteristics of patients with ET currently enrolled in MOST. Methods: MOST is a multicenter, noninterventional, prospective, observational study in patients with a clinical diagnosis of specific risk categories of MF or ET (NCT02953704). Eligible patients with ET included high-risk patients (≥ 60 years of age and/or a history of thromboembolic events [TEs]), or low-risk patients currently receiving ET-directed therapy. Key exclusion criteria included participation in blinded investigational drug studies, life expectancy ≤ 6 months, or diagnosis of other malignancy. Data regarding disease and clinical characteristics are collected at usual-care visits over a planned 36-month observation period. Patient demographics and clinical characteristics at enrollment were described with descriptive statistics. Results: At data cutoff (May 18, 2018), 793 eligible patients were enrolled from 85 sites since November 29, 2016. The median age at enrollment was 70 (range, 24-95) years, 66.5% were female, and 89.8% were Caucasian. The median time from ET diagnosis to enrollment was 4.2 (range, 0.0-42.1) years with a proportion of patients diagnosed within 1 year (19.5%), 1 to < 5 years (35.0%), 5 to < 10 years (21.7%), or ≥ 10 years (23.8%) of enrollment. Approximately 40% of patients were retired and 42.7% were working full- or part-time at enrollment. A total of 212 patients (26.7%) had a history of TE at the time of enrollment. The type of TE was available for 148 patients, the most common was arterial events (53.4%); 33.1% had venous, and 13.5% of patients had both arterial and venous events. Six hundred and eighty-eight patients (86.8%) were classified as high-risk. Assessments at the time of ET diagnosis, among evaluable patients, included bone marrow biopsy (51.4%; 393/765) and mutational testing (77.2%; 590/764). Three hundred and forty-nine patients had mutation test results reported at the time of diagnosis; of patients with JAK2 V617F test results reported at the time of diagnosis (n = 313), 78.6% were positive for JAK2 V617F (Table 1). Laboratory values and peripheral blood counts were reported for patients with available data (Table 2). The majority of patients (87.9%) had received at least 1 ET-directed therapy prior to enrollment, which in some cases was the same medication the patient was receiving at the time of enrollment. At the time of enrollment, 740 patients (93.3%) were receiving at least 1 current ET-directed therapy, including HU (71.6%; 530/740), anagrelide (13.1%; 97/740), ruxolitinib (4.7%; 35/740), interferon (3.0%; 22/740), and busulfan (0.3%; 2/740). Of 793 patients, the most frequently occurring relevant comorbid conditions were hypertension (52.7%), history of smoking (44.7%), and hyperlipidemia (24.1%). Among 761 patients with ET-related symptoms assessed at diagnosis, the most common symptoms documented by healthcare providers included constitutional (22.9%), vasomotor (16.0%), and spleen-associated symptoms (3.9%), and pruritus (2.6%). Conclusions: Prior real-world data in ET has predominately been generated outside of the United States or has been reported from single institutional experiences. The MOST study will provide a more complete picture of the patient characteristics and outcomes of patients receiving ET-directed therapy in the United States. Ultimately, these data will be important for determining ET treatment gaps and areas of unmet need. Disclosures Yacoub: Cara Therapeutics: Equity Ownership; Inycte: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Ardelyx, INC.: Equity Ownership; Seattle Genetics: Honoraria, Speakers Bureau; Dynavax: Equity Ownership. Verstovsek:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Italfarmaco: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy. Shao:ASH: Membership on an entity's Board of Directors or advisory committees; ASCO: Membership on an entity's Board of Directors or advisory committees. Agrawal:Incyte: Speakers Bureau. Sivaraman:Incyte: Employment. Colucci:Incyte: Employment, Equity Ownership. Yao:Incyte: Employment. Mascarenhas:Celgene: Membership on an entity's Board of Directors or advisory committees; Promedior: Research Funding; CTI Biopharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Merck: Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Research Funding; Janssen: Research Funding.

scholarly journals Community Versus Academic Practice in Essential Thrombocythemia and Myelofibrosis: Differences in Clinical Characteristics, Diagnosis, Treatment Patterns, and Symptom Burden (Analysis of Data from the MOST Study)

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1497-1497
Author(s):  
Roger Lyons ◽  
David Lessen ◽  
Salman Fazal ◽  
Robyn Scherber ◽  
Patricia Kalafut ◽  
...  
Keyword(s):  
Patient Education ◽  
Observational Study ◽  
Essential Thrombocythemia ◽  
Stock Options ◽  
Research Funding ◽  
Symptom Burden ◽  
The United States ◽  
Education Level ◽  
Treatment Patterns ◽  
Privately Held

Abstract Background: The Myelofibrosis and Essential Thrombocythemia Observational STudy (MOST) (NCT02953704) is an ongoing multicenter, noninterventional, longitudinal, prospective, observational study in patients with essential thrombocythemia (ET) or myelofibrosis (MF) enrolled in academic and community centers (ACs and CCs) throughout the United States. This analysis examined patient baseline characteristics, diagnosis, treatment patterns, and symptom burden in ACs vs CCs. Methods: Eligible patients had high-risk (HR) (≥60 years of age and/or thromboembolic history) or low-risk (LR) ET (if receiving ET-directed therapy [not including aspirin only]); patients with MF (≥18 years of age) had LR MF or intermediate-1 (INT-1)-risk (INT-1R) MF by reason of age &gt;65 years alone. Baseline data regarding demographics, diagnosis, treatment, and symptom burden were collected as previously characterized (Yacoub A. Clin Lymphoma Myeloma Leuk. 2021;21:461-69); this analysis compared data from 24 ACs with those from 82 CCs. Results: In the ET cohort, 1182 of 1237 patients were evaluable for this analysis, with 273 AC (17% LR; 83% HR) and 909 CC (12% LR; 88% HR) enrollees. In the MF cohort, 203 of 232 patients were evaluable for analysis, with 92 AC (50% LR; 50% INT-1R) and 111 CC (35% LR; 65% INT-1R) enrollees. Across both the ET and MF cohorts, the mean (SD) age was significantly higher in patients enrolled at CCs vs ACs (Table 1). In the ET cohort, significant differences were observed in patient race and ethnicity (both P&lt;0.01) and significantly higher proportions of patients were White (P&lt;0.05) and of Hispanic or Latino ethnicity (P&lt;0.05) in CCs vs ACs. Significant differences were also observed in patient education level (P&lt;0.0001) and employment status (P=0.0001) between ACs vs CCs, and a significantly higher proportion of patients were retired in CCs vs ACs (P=0.0001). In the MF cohort, a significant difference in ethnicity was observed (P&lt;0.05) and a significantly higher proportion of patients were of Hispanic or Latino ethnicity in CCs vs ACs (P&lt;0.05). Significant differences were also observed in patient education level in ACs vs CCs (P=0.0002), and a higher proportion of patients were retired in CCs vs ACs (P&gt;0.05). At diagnosis, the proportion of patients with ET or MF reported to have undergone bone marrow evaluation and mutation testing for myeloproliferative neoplasms in ACs vs CCs was not significantly different at the 0.05 level. At enrollment, leukopenia was significantly more common in patients with ET enrolled at ACs vs CCs (P&lt;0.01). In the ET cohort, the proportion of HR patients who were receiving ET-directed monotherapy were similar between ACs and CCs (Table 1). Compared with ACs, higher proportions of LR and HR patients were receiving anagrelide, higher proportions of LR and HR patients were receiving hydroxyurea, and lower proportions of LR and HR patients were receiving interferon in the CCs. The proportion of patients with ≥1 ET-related physician-reported symptom was higher among ACs vs CCs (P=0.0001). In the MF cohort, the proportion of LR patients receiving MF-directed monotherapy was higher in ACs vs CCs, while this proportion was lower in INT-1R patients in ACs vs CCs (Table 1). Compared with ACs, a higher proportion of LR patients were receiving anagrelide and ruxolitinib, a higher proportion of INT-1R patients were receiving hydroxyurea, and a lower proportion of LR and INT-1R patients were receiving interferon in CCs. The proportion of patients with ≥1 MF-related physician-reported symptoms was similar among ACs vs CCs (P&gt;0.05). Conclusion: These real-world data from MOST demonstrate that care was generally similar between ACs and CCs. Although there were key statistical differences in demographics (eg, age, ethnicity, and education level), disease features, and treatment history, the clinical significance of these differences remains unclear. Some of these differences (eg, demographics), however, could be attributed to the geographic location of the enrollee. Nevertheless, the older population and significant minority populations observed in CCs may represent a key population for clinical trial recruitment. Further investigation into these differences will help assess and enhance ET and MF disease management across sites. Figure 1 Figure 1. Disclosures Lessen: Astellas Pharma: Research Funding; Exact Sciences: Research Funding; Incyte Corporation: Consultancy, Research Funding, Speakers Bureau; Pfizer: Research Funding; Amgen: Speakers Bureau; Bayer: Consultancy, Speakers Bureau. Fazal: Sanofi Genzyme: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Karyopharm Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau; Janssen Oncology: Consultancy, Honoraria, Speakers Bureau; Taiho Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Speakers Bureau; Stemline Therapeutics: Consultancy, Honoraria, Speakers Bureau; Incyte: Consultancy, Honoraria, Speakers Bureau; Glaxo Smith Kline: Consultancy, Honoraria, Speakers Bureau; Gilead Sciences: Consultancy, Honoraria, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Speakers Bureau; AMGEN: Consultancy, Honoraria, Speakers Bureau; Agios: Consultancy, Honoraria, Speakers Bureau. Scherber: Incyte Corporation: Current Employment, Current holder of stock options in a privately-held company. Kalafut: Incyte: Current Employment, Current holder of stock options in a privately-held company. Ren: Incyte: Current Employment, Current holder of stock options in a privately-held company. Ritchie: NS Pharma: Research Funding; ARIAD Pharmaceuticals: Ended employment in the past 24 months, Speakers Bureau; Novartis: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria; Protaganist: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Research Funding; Astellas: Consultancy, Research Funding; Celgene/BMS: Consultancy, Other: travel support, Speakers Bureau; Abbvie: Consultancy, Honoraria; Incyte: Consultancy, Honoraria, Speakers Bureau; Jazz: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding.

scholarly journals Symptom Burden and Quality of Life in High-Risk Essential Thrombocythemia and Polycythemia Vera Patients Receiving Hydroxyurea or Pegylated Interferon Alfa-2a: Results of Myeloproliferative Neoplasms Research Consortium (MPN-RC) 111 and 112 Trials

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 19-21
Author(s):  
Gina L. Mazza ◽  
Carolyn Mead-Harvey ◽  
John Mascarenhas ◽  
Abdulraheem Yacoub ◽  
Ronald Hoffman ◽  
...  
Keyword(s):  
High Risk ◽  
Research Funding ◽  
Myeloproliferative Neoplasms ◽  
Symptom Burden ◽  
Pegylated Interferon ◽  
Abdominal Discomfort ◽  
Publicly Traded ◽  
Open Label ◽  
Early Satiety ◽  
High Baseline

Introduction Essential thrombocythemia (ET) and polycythemia vera (PV) patients suffer from various symptoms that worsen quality of life (QOL), yet serial data on symptom changes resulting from therapy are sparse in the literature. Patient questionnaires from 2 large multicenter trials (MPN-RC 111, 112) were used to assess change in symptom burden and QOL over 12 months and impact of baseline symptom burden on subsequent change in ET / PV patients on hydroxyurea (HU) or pegylated interferon alfa-2a (PEG). Methods Trials MPN-RC 111 was a single-arm, open-label, phase II trial evaluating response to PEG in high-risk ET / PV patients with HU resistance/intolerance or splanchnic vein thrombosis (SVT; NCT01259817). MPN-RC 112 was a randomized, open-label, phase III trial comparing response to PEG versus HU in cytoreductive therapy naïve high-risk ET / PV patients diagnosed &lt; 5 years ago (NCT01258856). Measures Patients reported disease-related symptoms via the validated Myeloproliferative Neoplasms Symptom Assessment Form (MPN-SAF), QOL via the European Organisation for the Research and Treatment of Cancer Core QOL Questionnaire (EORTC QLQ-C30), and (if applicable) PEG-related symptoms (flu-like symptoms, injection site irritation, blurry vision, vision change, flushing) at baseline, 3, 6, 9, and 12 months. Analysis Mixed models assessed mean changes from baseline in the MPN-SAF Total Symptom Score (TSS), MPN-SAF items, QOL, and PEG-related symptoms in MPN-RC 111, 112 PEG, and 112 HU patients. Mixed models also assessed the impact of baseline symptom burden (high [TSS ≥ 20] versus low) on subsequent change in PEG (MPN-RC 111 and 112) and HU patients. Results Patients Of the 135 enrolled MPN-RC 111 patients, 20 with SVT and 1 with no questionnaires were excluded. Of the remaining 114, 64 (56%) / 50 (44%) had ET / PV. Patients were 51% / 48% female. Median age was 65 / 64 years, and median time since diagnosis was 38 / 55 months. 31% / 22% had prior thrombosis, and 19% / 56% had splenomegaly. Of the 168 enrolled MPN-RC 112 patients (82 PEG, 86 HU), 2 with no questionnaires were excluded. Of the remaining 166, 79 (48%) / 87 (52%) had ET / PV. Patients were 50% / 33% female. Median age was 60 / 62 years, and median time since diagnosis was 3 / 3 months. 25% / 29% had prior thrombosis, and 11% / 37% had splenomegaly. Symptoms Questionnaire completion rates ranged from 90 - 99%, 87 - 100%, and 75 - 96% for on-treatment MPN-RC 111, 112 PEG, and 112 HU patients. At baseline, TSS (0 [absent] - 100 [worst imaginable]) and QOL (0 [very poor] - 100 [excellent]) means (SDs) were 19.5 (18.4) and 71.6 (20.1) for MPN-RC 111, 17.0 (13.6) and 67.9 (24.3) for MPN-RC 112 PEG, and 14.6 (11.4) and 73.8 (18.8) for MPN-RC 112 HU patients. On average, MPN-RC 111 patients had significant improvement of TSS, fatigue, abdominal pain, abdominal discomfort, dizziness, numbness, night sweats, and fever; MPN-RC 112 PEG patients had significant worsening of fever; and MPN-RC 112 HU patients had significant worsening of inactivity (no mean changes indicating improvement were observed). PEG patients had significant worsening of PEG-related symptoms. The greatest improvements occurred in the 46 (40%), 27 (33%), and 23 (28%) MPN-RC 111, 112 PEG, and 112 HU patients with high baseline symptom burden. On average, PEG patients with high baseline symptom burden had significant improvement of TSS, fatigue, early satiety, abdominal pain, abdominal discomfort, inactivity, headache, concentration, dizziness, numbness, insomnia, cough, night sweats, itching, bone pain, fever, weight loss, and QOL, while those with low baseline symptom burden had significant worsening of TSS, early satiety, headache, itching, and bone pain. On average, HU patients with high baseline symptom burden had significant improvement of TSS, early satiety, abdominal discomfort, headache, dizziness, numbness, insomnia, itching, and weight loss, while those with low baseline symptom burden had significant worsening of TSS, early satiety, abdominal discomfort, inactivity, concentration, and sexual desire/function (Figures 1 and 2). Conclusions Although no statistical comparisons were made across trials, overall improvements were seen in MPN-RC 111 but not 112. Patients with high baseline symptom burden experienced the greatest improvements in symptom burden and QOL during treatment with PEG or HU, which may explain the improvements seen in the more advanced patients in MPN-RC 111 compared to 112. Disclosures Mascarenhas: Celgene, Prelude, Galecto, Promedior, Geron, Constellation, and Incyte: Consultancy; Incyte, Kartos, Roche, Promedior, Merck, Merus, Arog, CTI Biopharma, Janssen, and PharmaEssentia: Other: Research funding (institution). Yacoub:Dynavax: Current equity holder in publicly-traded company; Ardelyx: Current equity holder in publicly-traded company; Cara Therapeutics: Current equity holder in publicly-traded company; Hylapharm: Current equity holder in private company; Incyte: Speakers Bureau; Agios: Honoraria, Speakers Bureau; Novartis: Speakers Bureau; Roche: Other: Support of parent study and funding of editorial support. Hoffman:Protagonist: Consultancy; Forbius: Consultancy; Novartis: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Dompe: Research Funding. Silver:PharmaEssentia: Speakers Bureau. Mesa:Bristol Myers Squibb: Research Funding; Incyte: Research Funding; AbbVie: Research Funding; Samus Therapeutics: Research Funding; Genentech: Research Funding; CTI BioPharma: Research Funding; Promedior: Research Funding; Sierra Oncology: Consultancy; LaJolla Pharmaceutical Company: Consultancy; Novartis: Consultancy.

scholarly journals Rusfertide (PTG-300) Induction Therapy Rapidly Achieves Hematocrit Control in Polycythemia Vera Patients without the Need for Therapeutic Phlebotomy

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 390-390
Author(s):  
Yelena Ginzburg ◽  
Kamini Kirubamoorthy ◽  
Sinari Salleh ◽  
Sung-Eun Lee ◽  
Jae Hoon Lee ◽  
...  
Keyword(s):  
High Risk ◽  
Adverse Events ◽  
Polycythemia Vera ◽  
Research Funding ◽  
Safety Monitoring ◽  
Data Safety Monitoring Board ◽  
Low Risk ◽  
Publicly Traded ◽  
The Mean ◽  
Mean Time

Abstract Background. Polycythemia (PV) patients with hematocrit above 45% are at increased risk of thrombotic complications and are treated with phlebotomy and/or cytoreductive therapy to reach a hematocrit target below 45%. Rusfertide (PTG-300) is a peptidic mimetic of hepcidin that is being developed for treatment of polycythemia vera (PV). A Phase 2 trial has indicated that rusfertide is effective at reducing the number of phlebotomies and maintaining hematocrit below 45% without phlebotomy in PV patients who are either high-risk or low-risk, patients treated with cytoreductive therapy (hydroxyurea, interferon, ruxolitinib) and patients treated with phlebotomy alone (Kremyanskaya, ASH 2020). The current trial (PTG-300-08) tested the ability of rusfertide to normalize hematocrit in PV patients with elevated hematocrit without instituting phlebotomy treatment to normalize hematocrit to below 45% in PV patients without requiring phlebotomy and/or cytoreductive treatment. Methods. Eligible study subjects were diagnosed with PV (in accordance with the WHO 2016 criteria), had baseline hematocrit above 48%, and a history of 3 or more hematocrit values above 48% in the year prior to enrollment. High-risk and low-risk subjects treated with phlebotomy alone or with concurrent cytoreductive therapy were eligible. Rusfertide was added on to each subject's current therapy. The initial rusfertide dose was 40 mg administered subcutaneously twice weekly. When each subject's hematocrit was below 45%, the dosing schedule was changed to weekly and the rusfertide dose was adjusted to maintain hematocrit below 45%. Results. Sixteen subjects (12 male and 4 females) have been enrolled. The mean age is 56.1 years; the mean time since diagnosis is 3.74 years; 10 subjects are low risk PV; 12 subjects are receiving concurrent hydroxyurea and 4 subjects were not receiving cytoreductive therapy. Baseline values (mean, min-max) HCT (51.0%, 47.4 - 59), WBC (12,338/µL, 7,000 - 24,600), RBCs (5.9x10 6/µL, 4.3 - 7.6), platelets (486,500/µL, 242,000 - 904,000). All subjects had rapid decreases in hematocrit to below 45% without the use of phlebotomy (Figure 1a). Hematocrit levels remained well controlled after falling below 45% as investigators reduced rusfertide dose to maintenance once weekly regimen. Hemoglobin (Figure 1b) fell rapidly. Erythrocyte counts (Figure 1c) also fell rapidly, indicating that decreased hematocrit is due to decreased erythrocytosis. For the 11 subjects with adequate follow-up, the mean rate of absolute hematocrit decrease was 1.76% per week (median: 1.81%/week; min - max: 0.65 - 2.69%) and the mean time to reach goal hematocrit below 45% was 4.79 weeks (median: 4.14 weeks, min - max: 3.57 - 8.14). Eight subjects reported adverse events (AEs). Injection site reactions (ISRs) occurred in 7 subjects and were mild or moderate in severity. The most common ISRs were erythema (n=7), induration (n=5) and pruritis (n=2). Adverse events other than ISRs that occurred in 2 or more subjects were hypertension (n=2), pyrexia (n=2) and thrombocytosis (n=2). There were two serious adverse events (worsening migraine and pleuritic chest pain) and both were considered unrelated to rusfertide. Overall, rusfertide was well tolerated. Conclusions. This study demonstrates that induction therapy with twice weekly rusfertide administration was effective in rapidly achieving target hematocrit below 45% without phlebotomy in all PV patients which was then successfully maintained with weekly rusfertide treatment. Moreover, the twice weekly injections of rusfertide used to rapidly lower hematocrit levels were safe and well tolerated. Key words: Hepcidin, Hematocrit, Rusfertide, PTG-300, Polycythemia Vera, PV, Therapeutic Phlebotomy Figure 1 Figure 1. Disclosures Gupta: Protagonist Therapeutics: Current Employment. Valone: Protagonist Therapeutics: Consultancy, Current equity holder in publicly-traded company. Khanna: Protagonist: Current Employment, Current equity holder in publicly-traded company. Modi: Protagonist Therapeutics: Current Employment. Hoffman: Kartos Therapeutics, Inc.: Research Funding; Protagonist Therapeutics, Inc.: Consultancy; Novartis: Other: Data Safety Monitoring Board, Research Funding; AbbVie Inc.: Other: Data Safety Monitoring Board, Research Funding.

scholarly journals REVEAL: Characteristics of Patients with Polycythemia Vera Who Were Diagnosed within 6 Months of Enrollment

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5370-5370
Author(s):  
Aaron T. Gerds ◽  
Ivy Altomare ◽  
Philomena Colucci ◽  
Dilan Paranagama ◽  
John M Burke
Keyword(s):  
High Risk ◽  
Polycythemia Vera ◽  
Research Funding ◽  
Clinical Characteristics ◽  
Prospective Observational Study ◽  
Low Risk ◽  
Early Satiety ◽  
High Risk Disease ◽  
History Of ◽  
Equity Ownership

Background Polycythemia vera (PV), characterized by erythrocytosis and JAK2 mutations, is associated with increased morbidity and mortality. Patients (pts) are at risk for thrombotic events and experience symptoms (sxs) that may impact quality of life. Data describing the clinical characteristics of pts with PV at the time of diagnosis (dx) are limited. The Prospective Observational Study of Patients with Polycythemia Vera in US Clinical Practices (REVEAL) is a multicenter, prospective, observational study designed to collect data on disease burden, clinical management, and pt-reported outcomes (PROs) of adult pts (aged ≥18) with PV. This analysis describes pt demographic and clinical characteristics, treatment patterns, and sxs of newly dxed pts with PV. Methods Pts enrolled in REVEAL who were dxed ≤6 months prior to enrollment were included in this analysis. Descriptive statistics were used to summarize pt demographic and clinical characteristics, tests at dx, and management patterns at dx. Sxs were assessed with a validated PRO instrument: the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS). Mean and standard deviation for individual sx scores and total sx score (TSS) at enrollment are reported. Results Of the 2510 pts enrolled in REVEAL, 321 dxed within 6 months of enrollment were included in this analysis. Median age at enrollment was 67.0 (range, 23.0-94.0) years, 54.8% were male, and most (74.5%) had high-risk disease (aged ≥60 years and/or history of thrombosis). The most common physician-reported symptoms at the time of presentation included fatigue (24.6%), pruritus (17.1%), insomnia (10.3%), and muscle aches/bone pain (9.7%). Of those pts reported to have undergone mutation testing at dx (n=201), 99.5% were JAK2V617F positive. A history of thrombosis was reported for 15.9% of pts (arterial, 8.1%; venous, 8.7%), and the most common relevant comorbidities were hypertension (58.6%), obesity (19.6%), and diabetes mellitus (15.9%). Of 188 pts with lab values within 1 month before dx, 95.2% had elevated (≥45%) hematocrit and 59.6% had elevated (>10 × 109/L) white blood cell counts. Most high-risk and low-risk pts were reported to have received phlebotomies within 6 months after dx (71.7% and 78.4%, respectively). A higher proportion of pts with high-risk disease initiated a pharmacologic therapy for PV compared with those who had low-risk disease (60.5% vs 23.9%); hydroxyurea (HU) was the most common cytoreductive therapy (n=151 [93.2%]). Most of these pts (n=137 [90.7%]) were still receiving HU 2 years after dx. Of those who initiated HU within 6 months of dx, 5.3% (n=8) received an alternative cytoreductive therapy following HU. A total of 287 pts provided PRO data at enrollment (Table 1). The most common pt-reported sxs were fatigue (77.2%), early satiety (61.1%), and inactivity (58.0%); the mean (SD) MPN-SAF TSS was 18.5 (15.6). The sxs with the highest reported mean (SD) scores were fatigue (3.4 [2.7]), inactivity (2.6 [2.9]), and early satiety (2.5 [2.6]) and were largely similar between low-risk and high-risk pts. Conclusions Compared with all 2510 pts enrolled in REVEAL (Clin Lymphoma Myeloma Leuk 2018[18]12:788-95), this subgroup of 321 pts dxed within 6 months of enrollment was similar with respect to age and sex. However, in the newly dxed subgroup, a slightly lower proportion of pts (74.5%) had high-risk disease (77.3% of the full cohort). In the newly dxed subgroup, a higher proportion of pts (62.6%) underwent mutation testing (49.2% of all enrolled pts). The HU discontinuation rate early in the treatment course was approximately 9.3%, which is similar to the rate (6.3%) of HU discontinuation due to toxicity in patients with PV in a large, multicenter, MPN cohort (Am JHematol 2012[87]5:552-4). Sx burden in pts who completed the MPN-SAF TSS at enrollment was similar in the newly dxed pts (mean TSS, 18.5) and all pts enrolled in REVEAL (18.8; Clin Lymphoma Myeloma Leuk 2018[18]9:590-6); the most frequent pt-reported sxs (fatigue, early satiety, and inactivity) in this smaller pt subgroup were the same as those observed in the larger pt cohort. Overall, near the time of dx, a greater proportion of pts had low-risk disease. Despite this difference, the sx constellation and severity tends to be very similar to the larger cohort. It also appears that only a very small proportion of pts are unable to tolerate HU early on in the course of the disease. Disclosures Gerds: Sierra Oncology: Research Funding; Imago Biosciences: Research Funding; Incyte: Consultancy, Research Funding; CTI Biopharma: Consultancy, Research Funding; Pfizer: Consultancy; Celgene Corporation: Consultancy, Research Funding; Roche: Research Funding. Altomare:Novartis: Consultancy; Amgen: Consultancy; Incyte: Consultancy, Speakers Bureau; Rigel: Consultancy. Colucci:Incyte: Employment, Equity Ownership. Paranagama:Incyte: Employment, Equity Ownership. Burke:Roche/Genentech: Consultancy; Celgene: Consultancy; Gilead: Consultancy.

Do Patients with Post-Essential Thrombocythemia and Post-Polycythemia Vera Differ from Patients with Primary Myelofibrosis?

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4069-4069 ◽  
Author(s):  
Lucia Masarova ◽  
Naval Daver ◽  
Naveen Pemmaraju ◽  
Prithviraj Bose ◽  
Sherry Pierce ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
High Risk ◽  
Polycythemia Vera ◽  
Essential Thrombocythemia ◽  
Research Funding ◽  
Clinical Characteristics ◽  
Univariate Analysis ◽  
Primary Myelofibrosis ◽  
Secondary Malignancy ◽  
Jak2 Mutation

Abstract Introduction: Clinical characteristics of post-essential thrombocythemia/polycythemia vera myelofibrosis "post ET/PV-MF" are not well defined as for primary myelofibrosis "MF". Objective: We aimed to identify morphological, clinical and prognostic characteristics of patients with post ET/PV-MF seen at our center. Methods: Retrospective chart review of 1120 patients with MF - 766 primary MF, 354 post ET/PV-MF, who were referred to our institution between years 1984-2013 was performed; 92% presented after the year of 2000. Fisher's exact and Mann-Whitney test were used for categorical and continuous variables; Cox proportional hazard model and Kaplan-Meier curves with log rank test for correlation between the variables and survival. Survival analysis were calculated after censoring patients for stem cell transplantation "SCT" (n=92). Results: Overall median follow up was 36 months (0-411), 51% (n=573) patients had died. Progression to AML after median time of 32 months was not different between groups and occurred in 9.5% (n=106) patients over observation period of 5180 persons-years. Incidence rate was 3.4 cases per 100 persons-year. Causes of death were known in 55% of patients, and included progression of MF in 38% (n=122), infection in 27% (n=86), and other reasons with less than 10% occurrence (complications post SCT; secondary malignancy; other medical conditions). Demographics and disease characteristics are depicted in a table. 92% of patients were evaluable for karyotype; abnormalities were detected in 39% (n=404), of which 53% were unfavorable with monosomal (23%), complex (43%) and trisomy 8 (18%) being the most common. Molecularly high risk mutations "MHR" in genes ASXL1, EZH2, and IDH1/2 were positive in 35% of tested patients (n=161) regardless of presence of driver mutation. IPSS and DIPSS plus scores were similar between MF and post ET/PV-MF (with IPSS low in 8.7%, intermediate 1 in 19%, intermediate 2 in 28%, and high in 44%). By multivariate analysis, higher risk categories of IPSS and DIPSSplus predicted shorter overall survival "OS" for both cohorts (by DIPSSplus - high risk: HR 2.7, 95% CI 2.1-3.5; int-2: HR 1.6; 95% CI 1.3-2.0). Median OS stratified by IPSS was 160 (HR 1.8, 95%CI 1.0-3.0), 116 (HR 1.5, 95%CI 1.0 -1.5), 78 (HR 1.4, 95%CI 1.2-1.7) and 54 months, p=0.001. Univariate analysis identified age over 65, anemia, trombocytopenia, leukopenia, increased blasts, splenomegaly, constitutional symptoms, unfavorable karyotype, JAK2 mutation and triple negativity as predictors for inferior survival. Age over 65; hemoglobin below 10, platelets below 100 and peripheral blasts ≥1% showed significance for predicting OS by multivariate analysis. When stratified according to diagnosis, higher age, anemia, thrombocytopenia, high blasts, JAK2 positivity and triple negativity retained prognostic significance for MF whereas anemia, thrombocytopenia, and JAK2 mutation for post ET/PV-MF. Median OS was 73 months (range, 0.1-210) without difference between MF and post ET/PV-MF. Conclusion: Post ET/PV-MF does not appear to have substantial different clinical characteristics than primary MF. Table. Characteristics Total, number or median (% or range) MF, number or median (% or range) PET/PV-MF, number or median (% or range) Age 65 (20-89) 64 (20-88) 64 (27-89) Age > 65 552 (49) 367 (48) 185 (53) Males 675 (60%) 494 (65) 181 (51)* WBC 9.6 (0.4-361) 17.3 (5-19) 16.7 (5-18) WBC > 24 203 (18) 133 (18) 70 (20) WBC < 4 160 (14) 130 (17) 30 (8.5)* Plt 204 (3-2690) 237 (1-1364) 354 (6-2690)* Plt < 100 276 (25) 220 (29) 56 (16)* Hgb 10.5 (5-18) 10 (5-18) 11 (5-19)* Hgb < 10 462 (42) 329 (43) 133 (38)* Transfusion dependency 265 (24) 203 (27) 62 (18)* Blasts ≥ 1% 523 (47) 371 (49) 152 (43) Splenomegaly 668 (60) 459 (63) 209 (65) Symptoms 793 (71) 537 (70) 256 (73) LDH 1246 (189-10343) 1248 (189-10353) 1261 (205-8476) LDH > 620 958 (86) 640 (85) 318 (90)* JAK2 positive 586 (57) 371 (63) 215 (37)* MPL positive 19 (1.9) 16 (84) 3 (16)* CARL positive 53 (5) 27 (51) 26 (49)* Triple negative 26 (2.5) 21 (81) 5 (19)* *statistically significant differences (p<0.05) Disclosures Pemmaraju: Stemline: Research Funding; Incyte: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; LFB: Consultancy, Honoraria. Cortes:Novartis: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Teva: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; ARIAD Pharmaceuticals Inc.: Consultancy, Research Funding.

Abstract 2126: Twoaces (tia Work-up Asoutpatient: Assessment Of Clincal Efficacy And Safety)

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Jenifer Green ◽  
Connie Wolford ◽  
Jean Marc Olivot ◽  
Gregory Albers ◽  
James Castle
Keyword(s):  
High Risk ◽  
Observational Study ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk ◽  
Stroke Rate ◽  
Significant Stenosis ◽  
Non Invasive ◽  
Low Rate ◽  
Arterial Imaging

Background: Much controversy exists as to which TIA patients need to be admitted to the hospital for evaluation and treatment and which can be sent home. One commonly used trigae tool is the ABCD 2 score (Age, presenting Blood Pressure, Clinical symptoms and Duration, and Diabetes). Although this tool gives good information for determining populations at low risk (score of 0-3) and high risk (score of 6-7) of stroke after TIA, it leaves a large moderate risk population (score of 4-5) for whom no clear triage guidance can be given. As previous studies have found large artery atherosclerosis to be a potent risk factor for stroke after TIA, we attempted to further delineate low and high risk TIA populations with the addition of non-invasive arterial imaging to the ABCD 2 score. Methods: All patients referred to the Stanford Stroke Service for possible TIA within 72 hrs of symptom onset between July 2007 and February 2010, and all patients referred to the Highland Park Stroke Service for possible TIA within 72 hrs of symptom onset after October 2009 were screened for enrollment in this observational study. Exclusion criteria included age <18 years, use of TPA at initial presentation, and symptoms lasting >24 hours. 352 patients were invited to enroll, 3 refused. Of the 349 enrolled, follow-up was obtained in 346 patients at 30 days. Patients were placed into two groups: 1) those with ABCD 2 scores of 0-3 or scores of 4-5 AND no sign of hemodynamically significant stenosis in an artery within the distribution of the TIA (Low Risk Group); and 2) those with ABCD 2 scores of 6-7 or scores of 4-5 AND a hemodynamically significant stenosis in an artery within the distribution of the TIA (High Risk Group). Non-invasive arterial imaging included CT angiogram, MR angiogram, and carotid ultrasound - all used at the discretion of the treating physician. 30 day stroke rates with 95% confidence intervals were recorded. Results: Of the 346 patients enrolled, 295 (85.3%) fell into the "Low Risk Group" based on ABCD 2 scoring and non-invasive arterial imaging. Within that group, the stroke rate at 30 days was 1.0% (3 strokes, 95% CI 0.2-3.1%). Within the "High Risk Group", the stroke rate at 30 days was 5.9% (3 strokes, 95% CI 1.4-16.5%). Within the "Low Risk Group", all 3 of the strokes occurred in patients with ABCD 2 scores of 4-5 (3/133 patients - 2.3% stroke rate with 95% CI 0.5-6.7%). The overall stroke rate was 6/346 (1.7%, 95% CI 0.7-3.8%). Conclusions: In our observational study we found that the overall 30 day stroke rate after TIA was quite low. The percentage of all TIA patients falling into the “Low Risk Group” was quite high, and these patients had a particularly low rate of stroke at 30 days. Given the high number of "Low Risk" patients and the low rate of stroke in that group at 30 days, the vast majority of TIA patients could likely be safely evaluated in an rapid outpatient setting provided that the treating physician is confident of the diagnosis.

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