Treatment Patterns and Hydroxyurea Response Among Patients with Polycythemia Vera

Abstract Background: PV is a myeloproliferative neoplasm characterized by increased red cell mass and elevated hematocrit. Phlebotomy represents the initial treatment option to lower hematocrit with the goal of reducing the risk of thrombosis. However, many patients require cytoreductive therapy, HU being the most commonly used treatment. Based on European LeukemiaNet (ELN) guidelines, response to PV therapies includes clinicohematologic response (CHR) which is based on several laboratory parameters (hematocrit values, platelet count, white blood cell count) as well as disease-related symptoms. The aim of this study was to investigate the treatment patterns, outcomes, and unmet medical needs among patients with PV treated with HU in a real-world setting. Methods: A retrospective chart review of PV patients was conducted in the United States between April-July 2014. Oncologists and hematologists abstracted data from patient charts into an online survey. Physicians were eligible to participate if they spent ≥50% of their time on direct patient care and had ≥5 PV patients under their care in the past 12 months with at least 25% of whom had prior (if not current) HU experience. Initial individual qualitative interviews with a subset of eligible physicians (N=19) were conducted to inform the design of the survey instrument. A pilot test survey with 28 physicians meeting eligibility was conducted to demonstrate feasibility and included in the final analyses. Inclusion criteria for patient charts were: age≥18 years, alive at time of chart abstraction or deceased within the past 6 months, diagnosed with PV 3-15 years ago, received HU therapy for ≥2 months within the last 5 years, had medical record data 12 months pre- and post-HU initiation, and were not part of a PV-related clinical trial. Treatment history, lab values, disease symptoms, and healthcare resource utilization data were collected and reported descriptively. Results: A total 329 physicians participated (Hem Oncs=78.1%, Med Oncs=15.5%, and hematologists=6.4%) and provided information on 1309 PV patients. Almost two-thirds (62.3%) of patients were male, mean age was 62.5 years (SD=12.2), and mean time since diagnosis was 5.2 years (SD=2.8). Among those currently on HU therapy (n=1,080; 82.5%), mean duration of therapy was 47.0 months (SD=30.8) and mean daily dose was 984 mg (SD=674 mg). A total of 229 (17.5%) of patients had discontinued HU therapy. Prior to discontinuing HU treatment, mean therapy duration was 23.2 months (SD=24.5), and mean daily dose immediately prior to discontinuing was 991 mg (SD=689 mg); 27.3% (n=183) of patients had a dose adjustment in the 3 months prior to discontinuing (range: 1-8 adjustments). The most common reasons for HU discontinuation were elevated hematocrit (23.1%) and the presence of drug-related side effects (21.8%) (Figure 1). Among those currently on HU, a significant proportion had elevated blood counts above ELN response thresholds: 34.4% had hematocrit level ≥45%, 59.4% had platelet levels >400x109/L, and 58.2% had WBC >10x109/L. Two-thirds (66.3%) of patients had at least one elevated value, 40.3% had at least two elevated values, and 19.8% had all three elevated. The most commonly observed PV-related signs and symptoms were fatigue (62.2%) and splenomegaly (57.3%). Furthermore, among patients currently on HU therapy, almost half (46.2%) experienced new PV-related symptoms in the past 12 months, the most common of which fatigue (22.7%) and splenomegaly (19.5%) in the past 12 months. Conclusions: In our study, a significant number of patients with PV discontinued HU therapy due to a lack of effectiveness or tolerability. Of those still on HU therapy, the majority did not achieve ELN response criteria for CHR. Furthermore, nearly half of the patients experienced new PV-related symptoms fatigue and splenomegaly despite HU treatment. Consistent with other reports, these study findings demonstrate that despite HU treatment, many patients continue to have uncontrolled PV. These data further support the significant unmet medical need in PV, including the need for more effective treatment options. Figure 1. Reasons for discontinuation among those who discontinued HU (N=229). Figure 1. Reasons for discontinuation among those who discontinued HU (N=229). Disclosures Parasuraman: Incyte Corporation: Employment, Equity Ownership. Off Label Use: Ruxolitinib is a JAK1/JAK2 inhibitor approved for the treatment of patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis, post polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis. DiBonaventura:Incyte Corporation: Research Funding. Reith:Incyte Corporation: Employment, Equity Ownership. Concialdi:Incyte Corporation: Research Funding.

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Epidemiology of PNH and Real-World Treatment Patterns Following an Incident PNH Diagnosis in the US

Blood ◽

10.1182/blood-2019-125867 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3407-3407 ◽

Cited By ~ 2

Author(s):

Jessica J Jalbert ◽

Umesh Chaudhari ◽

Haixin Zhang ◽

Jonathan Weyne ◽

Jamile M. Shammo

Keyword(s):

Incidence Rate ◽

Real World ◽

Treatment Duration ◽

Research Funding ◽

The United States ◽

Treatment Patterns ◽

Employment Equity ◽

Equity Ownership ◽

Procedure Codes ◽

Rbc Transfusion

Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired, life-threatening blood disease. While PNH is known to be a rare disease, the incidence and prevalence of the condition has been described only in a few small studies. In addition, while the International PNH registry is a rich source of data on real-world PNH patients globally, it is not possible to estimate the incidence and prevalence of PNH directly from the registry. As complement inhibitors are becoming the standard of care for PNH treatment, we also sought to explore how patients are managed following an incident PNH diagnosis. The objective of this study was to estimate the incidence and prevalence of PNH and to describe real-world treatment patterns among patients newly diagnosed with PNH in the United States (US). Methods: We conducted a retrospective cohort study using Truven US MarketScan Commercial/Medicare data (1 Jan 2015 to 30 June 2018), an employer-sponsored insurance claims database including annually approximately 30 million insured patients and their dependents' complete longitudinal records of inpatient services, outpatient services, and prescription drug claims covered under a variety of fee-for-service and capitated health plans. While these data are considered nationally representative of Americans with employer-provided health insurance, data come mainly from large employers. To estimate prevalence, we identified patients with ≥ 1 PNH diagnosis (ICD10: D59.5) among persons continually enrolled in the databases in 2017. To estimate incidence, we required ≥1-year of baseline enrolment and no PNH diagnosis or eculizumab exposure, identified using national drug codes [NDC] or procedure codes for drug administration, during the baseline period. Person-time accrued post-baseline until PNH diagnosis, end of study period, or disenrollment. We stratified incidence and prevalence estimates by age and sex and described patients with incident PNH in terms of demographics, comorbidities, and past-year healthcare resource utilization. Using Kaplan-Meier estimators, we estimated incidence of eculizumab initiation, timing of initiation, treatment duration, and risk of discontinuation/treatment holiday (>42 days between eculizumab exposures [i.e. 14-day exposure period + 28-day grace period between infusions], the equivalent of missing 2 infusions assuming a bi-weekly infusion schedule for eculizumab) following the incident PNH diagnosis. While accounting for censoring, we also investigated patterns of red blood cell (RBC) transfusions, identified using procedure codes, in terms of incidence and timing of first transfusion following an incident PNH diagnosis. Results: The prevalence of PNH varied little between 2016 and 2017, from 12 to 13 per 1,000,000. The incidence rate over the study period was 5.7 per 1,000,000 person-years, representing 257 incident PNH cases. The incidence rate of PNH increased with age and was similar across sex. At diagnosis, mean age was 50.0 years (standard deviation [SD]: 18.6), 3.1% (8/257) were less than 18 years, 52.1% were women, 19.5% had a past-year diagnosis of aplastic anemia, 8.2% had a past-year diagnosis of myelodysplastic syndrome, 14.0% had a past-year RBC transfusion, and 31.5% had been hospitalized in the past-year. Over a mean follow-up time of 385.6 days (SD: 253.2), 10.3% (95% confidence interval [CI]: 6.3-14.1%) of patients initiated eculizumab on average 60.5 days (SD: 55.9) from PNH diagnosis. At 1 year, about one third of patients discontinued eculizumab or had taken a treatment holiday; average treatment duration was 328.2 days (SD:245.4). Cumulative incidence of RBC transfusions at 6 months and 1 year was 14.6% (10.1-18.9%) and 17.4% (12.2-22.3%), respectively. On average, the first RBC transfusion occurred within 63.6 days (SD: 114.4) of an incident PNH diagnosis. Conclusions: In routine clinical practice, only a minority of patients recently diagnosed with PNH are initiated on eculizumab. Among PNH patients treated with eculizumab, less than 70% remain on treatment after 1 year. Findings must be interpreted in the context of limitations including lack of information on clone size, symptom burden, measures of disease activity, or bone marrow failure state which may affect treatment course. Future studies should explore factors affecting eculizumab initiation and persistence on treatment. Disclosures Jalbert: Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Chaudhari:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Zhang:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Weyne:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Shammo:Incyte: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Alexion: Consultancy, Honoraria, Research Funding, Speakers Bureau; Onconova: Research Funding; Apellis: Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Speakers Bureau; Astex Pharma: Research Funding; Novartis: Consultancy, Honoraria; Otsuka: Consultancy, Honoraria; CTI Pharma: Research Funding.

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Disease and Clinical Characteristics of Patients with Myelofibrosis Enrolled in the MOST Study

Blood ◽

10.1182/blood-2019-122441 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4190-4190

Author(s):

Aaron T. Gerds ◽

Roger M. Lyons ◽

Philomena Colucci ◽

Patricia Kalafut ◽

Dilan Paranagama ◽

...

Keyword(s):

Research Funding ◽

Clinical Characteristics ◽

The United States ◽

Treatment Patterns ◽

Low Risk ◽

Normal Range ◽

Employment Equity ◽

Oncology Research ◽

Risk Patients ◽

Equity Ownership

Introduction: Myelofibrosis (MF) is a chronic Philadelphia chromosome-negative myeloproliferative neoplasm characterized by progressive bone marrow (BM) fibrosis, extramedullary hematopoiesis, splenomegaly, constitutional symptoms, and shortened survival. Data pertaining to the clinical characteristics and treatment patterns of patients with low-risk MF are limited; most studies have focused on patients with intermediate- and high-risk MF. The ongoing Myelofibrosis and Essential Thrombocythemia Observational STudy (MOST) was designed to characterize the demographics, disease burden, patient-reported outcomes, and management of patients with MF or essential thrombocythemia (ET) in clinical practices throughout the United States (NCT02953704). This analysis describes demographic and clinical characteristics of patients with low-risk MF enrolled in MOST. Methods: MOST is an ongoing multicenter, non-interventional, longitudinal, prospective, observational study in patients with MF or ET. Eligible patients with MF were at least 18 years old and had low- or intermediate-1 (INT-1) risk by age alone according to the Dynamic International Prognostic Scoring System (DIPSS). Patients participating in blinded investigational drug trials, having life expectancy ≤6 months, or having other concurrent myeloid malignancies were excluded. Data from patient records were entered into an electronic case report form during usual-care visits over a planned 36-month observation period. Data were analyzed with descriptive statistics. Results: A total of 232 patients with MF were enrolled between November 29, 2016 and March 29, 2019 at 124 sites. Two-hundred patients with low-risk (n=77) or INT-1 risk by age alone (n=123) MF were included in this analysis (data cut-off date, June 17, 2019); 32 patients were excluded due to incorrect risk categorization (n=27) or unanswered prognostic factors at enrollment (n=5). At enrollment, the median age was 68 (range, 35-88) years, 58% were aged >65 years, 49% were women, and 89% were white. Thirteen patients (7%) had a documented family history of MF, ET, or polycythemia vera. Of 157 patients with manual spleen assessment at enrollment, 55 (35%) had palpable splenomegaly; median spleen length was 7 (range, 1‒22) cm in 35 patients with available measurements. The median time from MF diagnosis to enrollment was 1.7 (range, 0.0-37.7) years; most patients (75%) were diagnosed within 5 years of enrollment. Of patients with available data, 93% (185/200) were reported to have undergone BM biopsy/aspiration and 82% (162/198) had mutation testing (MT) at the time of diagnosis; most patients had received both BM biopsy and MT (151/196 [77%]). Data from MT conducted prior to or within 30 days of diagnosis were available for 142 patients (71%); 134/142 patients (94%) were tested for a JAK2 mutation, of whom 95/134 (71%) were positive (Table 1). At enrollment, approximately half of patients with available data (97/190 [51%]) had hemoglobin below normal range, and approximately one-third had platelets (68/188 [36%]) or leukocytes (58/186 [31%]) above normal range (Table 2). The most common signs reported at the time of enrollment included lactate dehydrogenase greater than the upper limit of normal (41%), palpable spleen (31%), and leukocytosis (>11 × 109/L; 24%). Across both risk groups, 111 patients (56%) were receiving MF-directed monotherapy at enrollment (low-risk, 43/77 [56%]; INT-1 by age alone, 68/123 [55%]). Low-risk patients received hydroxyurea (HU; 23/43 [54%]), ruxolitinib (15/43 [35%]), interferon (4/43 [9%]), or anagrelide (1/43 [2%]); INT-1 patients received ruxolitinib (30/68 [44%]), HU (28/68 [41%]), interferon (8/68 [12%]), or anagrelide (2/68 [3%]). Five patients (3%) were receiving >1 MF-directed therapy. Less than half of low- (34/77 [44%]) and INT-1- (50/123 [41%]) risk patients were receiving no MF-directed therapy at enrollment. Conclusion: These real-world data provide insight into the clinical characteristics, diagnosis, and treatment patterns of patients with low- or INT-1 risk (by age alone) MF in the United States. Data from this trial will help characterize the rate at which patients transition from low- or INT-1-risk disease to higher risk categories of disease and how management is affected by disease progression. Disclosures Gerds: Sierra Oncology: Research Funding; Imago Biosciences: Research Funding; Incyte: Consultancy, Research Funding; Celgene Corporation: Consultancy, Research Funding; CTI Biopharma: Consultancy, Research Funding; Pfizer: Consultancy; Roche: Research Funding. Lyons:Texas Oncology: Equity Ownership; Amgen: Consultancy; McKesson: Other: Leadership. Colucci:Incyte: Employment, Equity Ownership. Kalafut:Incyte: Employment, Equity Ownership. Paranagama:Incyte: Employment, Equity Ownership. Verstovsek:Promedior: Research Funding; Blueprint Medicines Corp: Research Funding; CTI BioPharma Corp: Research Funding; Genetech: Research Funding; Pragmatist: Consultancy; Pharma Essentia: Research Funding; Astrazeneca: Research Funding; Ital Pharma: Research Funding; Protaganist Therapeutics: Research Funding; Constellation: Consultancy; Incyte: Research Funding; Roche: Research Funding; NS Pharma: Research Funding; Celgene: Consultancy, Research Funding; Gilead: Research Funding; Novartis: Consultancy, Research Funding; Sierra Oncology: Research Funding.

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Treatment-Related Symptoms and Impact on Health-Related Quality of Life in AL Amyloidosis

Blood ◽

10.1182/blood.v128.22.4753.4753 ◽

2016 ◽

Vol 128 (22) ◽

pp. 4753-4753

Author(s):

Martha Bayliss ◽

Michelle K. White ◽

Kristen McCausland ◽

Colin Oliver ◽

Spencer D. Guthrie

Keyword(s):

Research Funding ◽

The United States ◽

Functional Health ◽

Al Amyloidosis ◽

Point Scale ◽

Employment Equity ◽

The Past ◽

History Of ◽

Equity Ownership

Abstract Introduction:Light-chain (AL) amyloidosis is a rare disease characterized by misfolded amyloid protein deposits in tissues and vital organs. Although no medications to treat AL amyloidosis have yet been approved by the United States Food and Drug Administration or the European Medicines Agency, chemotherapy, stem cell transplantation (SCT), and immunomodulatory drugs are used off-label. These treatments can be associated with treatment-related symptoms (TRSs). The objective of this study is to describe the history of TRSs and their impact on treatment regimens and HRQoL among a diverse sample of patients with AL amyloidosis. Methods: We report data from a non-interventional cohort of community-based patients with self-reported AL amyloidosis. Patients who completed a baseline and six-month follow-up online survey to assess TRSs and HRQoL were included in this analysis (n=226). TRSs were assessed among ever treated patients (n=216) and patients who were treated in the past year (recently treated, n=111). The following aspects of TRSs were captured: 1) prevalence of TRSs; 2) consequences of recent TRSs (discontinuation of a treatment; reduction of a treatment; or maintenance of treatment despite TRSs); 3) severity of specific TRSs (five point scale with a symptom checklist: none, mild, moderate, severe, very severe); and 4) ability to tolerate current AL amyloidosis treatment (based on a 4 point scale from "extremely poorly" to "very well"). A three-level categorical variable (i.e. better, same, worse) was derived to classify individuals by how they ranked their ability to tolerate their treatment at baseline as compared to their ranking at follow-up. A generic measure of HRQoL, the SF-36v2 Health Survey® (SF-36v2), was used to measure eight domains and two component summary measures of functional health and well-being. Higher SF-36v2 scores represented better functioning. Changes in patients' ability to tolerate current treatments were evaluated in relation to changes in SF-36v2 scores using ANCOVA methods and controlling for baseline SF-36v2 scores. Results:Three-quarters (79%) of all treated patients reported ever having problems tolerating AL amyloidosis treatment, of which nearly half (47%) discontinued at least one treatment; half (51%,) reduced at least one treatment; and half (51%) reported tolerability problems which did not lead to changes in treatment. Patients reported, on average, 3 moderate-to-severe TRSs. The most commonly reported moderate-to-severe TRSs included: fatigue (65%), neuropathy (36%), diarrhea (34%), and nausea (33%). Among recently treated patients, 53% endorsed a ranking of less than "very good" ability to tolerate current treatment. Ability to tolerate current treatments improved in the past six months for approximately 32% of recently treated patients and declined in 16% of recently treated patients. On average, patients who reported an improvement in their ability to tolerate current treatments also reported positive changes in HRQoL. Conversely, patients who reported a decline in their ability to tolerate their current treatments reported declines in HRQoL. These associations were not significant; however, the patterns for most scales were in the expected directions (Figure 1). Conclusion : Overall, patients' reported ability to tolerate treatment was poor. Lifetime history of TRSs was high. Discontinuation of AL amyloidosis treatment was fairly common, though most patients were able to tolerate their current regimen. The high prevalence of treatment discontinuation and history of multiple AL amyloidosis treatments suggests that physicians and patients try a variety of treatments to balance tolerability and efficacy. Findings related to change in ability to tolerate treatment six months after the initial survey suggest a relationship with changes in HRQoL. In some cases, the changes in HRQoL approached established minimally important differences which can alert clinicians to actual changes in functioning. While this relationship should be further tested with larger samples and longer follow-up periods, these findings highlight the importance of assessing HRQoL during treatment for AL amyloidosis to better understand tolerability, and the need for more treatment options for AL amyloidosis, particularly those with favorable tolerability. Disclosures Bayliss: Prothena Biosciences Inc: Research Funding. White:Prothena Biosciences Inc: Research Funding. McCausland:Prothena Biosciences Inc: Research Funding. Oliver:Prothena Biosciences, Inc.: Employment, Equity Ownership. Guthrie:Prothena: Employment, Equity Ownership, Other: Leadership.

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Treatment Patterns and Outcomes in Elderly Patients with Newly Diagnosed Multiple Myeloma: Results from the Connect® MM Registry

Blood ◽

10.1182/blood-2019-126205 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3129-3129

Author(s):

Hans C. Lee ◽

Sikander Ailawadhi ◽

Cristina Gasparetto ◽

Sundar Jagannath ◽

Robert M. Rifkin ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Causes Of Death ◽

Age Groups ◽

Treatment Patterns ◽

Age Group ◽

Newly Diagnosed ◽

Employment Equity ◽

Advisory Committees ◽

Equity Ownership

Background: Multiple myeloma (MM) is common among the elderly, with 35% of patients (pts) diagnosed being aged ≥75 years (y). With increasing overall life expectancy, the incidence and prevalence of newly diagnosed and previously treated MM patients ≥80 y is expected to increase over time. Because elderly pts are often excluded from clinical trials, data focused on their treatment patterns and clinical outcomes are lacking. The Connect® MM Registry (NCT01081028) is a large, US, multicenter, prospective observational cohort study of pts with newly diagnosed MM (NDMM) designed to examine real-world diagnostic patterns, treatment patterns, clinical outcomes, and health-related quality of life patient-reported outcomes. This analysis reviews treatment patterns and outcomes in elderly pts from the Connect MM Registry. Methods: Pts enrolled in the Connect MM registry at 250 community, academic, and government sites were included in this analysis. Eligible pts were adults aged ≥18 y with symptomatic MM diagnosed ≤2 months before enrollment, as defined by International Myeloma Working Group criteria; no exclusion criteria were applied. For this analysis, pts were categorized into 4 age groups: <65, 65 to 74, 75 to 84, and ≥85 y. Pts were followed from time of enrollment to the earliest of disease progression (or death), loss to follow-up, or data cutoff date of February 7, 2019. Descriptive statistics were used for baseline characteristics and treatment regimens. Survival outcomes were analyzed using Cox regression. Time to progression (TTP) analysis excluded causes of death not related to MM. Results: Of 3011 pts enrolled (median age 67 y), 132 (4%) were aged ≥85 y, and 615 (20%) were aged 75-84 y at baseline. More pts aged ≥85 y had poor prognostic factors such as ISS stage III disease and reduced hemoglobin (<10 g/dL or >2 g/dL <LLN) compared with other age groups, although no notable differences between creatinine and calcium levels were observed across age groups (Table). A lower proportion of elderly pts (75-84 and ≥85 y) received triplet regimens as frontline therapy. More elderly pts received a single novel agent, whereas use of 2 novel agents was more common in younger pts (Table). The most common frontline regimens among elderly pts were bortezomib (V) + dexamethasone (D), followed by lenalidomide (R) + D, whereas those among younger pts included RVD, followed by VD and CyBorD (Table). No pt aged ≥85 y, and 4% of pts aged 75-84 y received high-dose chemotherapy and autologous stem cell transplant (vs 61% in the <65 y and 37% in the 65-74 y age group). The most common maintenance therapy was RD in pts ≥85 y (although the use was low) and R alone in other age groups (Table). In the ≥85 y group, 27%, 10%, and 4% of pts entered 2L, 3L, and 4L treatments respectively, vs 43%, 23%, and 13% in the <65 y group. Progression-free survival was significantly shorter in the ≥85 y age group vs the 75-84 y age group (P=0.003), 65-74 y age group (P<0.001), and <65 y age group (P<0.001; Fig.1). TTP was significantly shorter in the ≥85 y group vs the <65 y group (P=0.020); however, TTP was similar among the 65-74 y, 75-84 y, and ≥85 y cohorts (Fig. 2). Overall survival was significantly shorter in the ≥85 y group vs the 75-84 y, 65-74 y, and <65 y groups (all P<0.001; Fig. 3). The mortality rate was lowest (46%) during first-line treatment (1L) in pts aged ≥85 y (mainly attributed to MM progression) and increased in 2L and 3L (47% and 54%, respectively); a similar trend was observed in the younger age groups. The main cause of death was MM progression (29% in the ≥85 y vs 16% in the <65 y group). Other notable causes of death in the ≥85 y group included cardiac failure (5% vs 2% in <65 y group) and pneumonia (5% vs 1% in <65 y group). Conclusions: In this analysis, elderly pts received similar types of frontline and maintenance regimens as younger pts, although proportions varied with decreased use of triplet regimens with age. Considering similarities in TTP across the 65-74 y, 75-84 y, and ≥85 y cohorts, these real-world data support active treatment and aggressive supportive care of elderly symptomatic pts, including with novel agents. Additionally, further clinical studies specific to elderly patients with MM should be explored. Disclosures Lee: Amgen: Consultancy, Research Funding; GlaxoSmithKline plc: Research Funding; Sanofi: Consultancy; Daiichi Sankyo: Research Funding; Celgene: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Ailawadhi:Janssen: Consultancy, Research Funding; Takeda: Consultancy; Pharmacyclics: Research Funding; Amgen: Consultancy, Research Funding; Celgene: Consultancy; Cellectar: Research Funding. Gasparetto:Celgene: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; Janssen: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; BMS: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed . Jagannath:AbbVie: Consultancy; Merck & Co.: Consultancy; Bristol-Myers Squibb: Consultancy; Karyopharm Therapeutics: Consultancy; Celgene Corporation: Consultancy; Janssen Pharmaceuticals: Consultancy. Rifkin:Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Durie:Amgen, Celgene, Johnson & Johnson, and Takeda: Consultancy. Narang:Celgene: Speakers Bureau. Terebelo:Celgene: Honoraria; Jannsen: Speakers Bureau; Newland Medical Asociates: Employment. Toomey:Celgene: Consultancy. Hardin:Celgene: Membership on an entity's Board of Directors or advisory committees. Wagner:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; American Cancer Society: Other: Section editor, Cancer journal. Omel:Celgene, Takeda, Janssen: Other: Patient Advisory Committees. Srinivasan:Celgene: Employment, Equity Ownership. Liu:TechData: Consultancy. Dhalla:Celgene: Employment. Agarwal:Celgene Corporation: Employment, Equity Ownership. Abonour:BMS: Consultancy; Celgene: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Janssen: Consultancy, Research Funding.

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A Phase I Trial of Janus Kinase (JAK) Inhibition with INCB039110 in Acute Graft-Versus-Host Disease (aGVHD)

Blood ◽

10.1182/blood.v128.22.390.390 ◽

2016 ◽

Vol 128 (22) ◽

pp. 390-390 ◽

Cited By ~ 8

Author(s):

Mark A. Schroeder ◽

H. Jean Khoury ◽

Madan Jagasia ◽

Haris Ali ◽

Gary J. Schiller ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Janus Kinase ◽

Cell Transplant ◽

Employment Equity ◽

Advisory Committees ◽

Daily Dose ◽

Equity Ownership ◽

Grade 3 ◽

Steroid Refractory

Abstract Background: Corticosteroids are considered standard first-line systemic therapy for patients with aGVHD, but this approach is effective in only approximately half of all cases. For patients who progress or do not respond to corticosteroids, no specific agent has been identified as standard, and regimens are typically selected based on investigator experience and patient co-morbidities. In preclinical models, JAK inhibition has been shown to impair production of cytokines as well as the differentiation and trafficking of T cells implicated in the pathogenesis of aGVHD. Retrospective studies have suggested that JAK1/JAK2 inhibition with ruxolitinib treatment provides clinical benefit in patients with steroid-refractory GVHD (Zeiser et al, Leukemia 2015;29:2062-2068). Herein, we report preliminary safety results from a prospective randomized, parallel-cohort, open-label phase 1 trial evaluating the potent and selective JAK 1 inhibitor INCB039110 in patients with aGVHD. Methods: Male or female patients 18 years or older who underwent their first allo-hematopoietic stem cell transplant (HSCT) from any donor source and developed grades IIB-IVD aGVHD were eligible for the study. Patients were randomized 1:1 to either a 200 or 300 mg oral daily dose of INCB039110 in combination with corticosteroids, and were stratified based on prior treatment status (treatment-naive [TN] versus steroid-refractory [SR]). The primary endpoint of the study was safety and tolerability; secondary endpoints included overall response rate at Days 14, 28, 56, and 100, non-relapse mortality, and pharmacokinetic (PK) evaluations. Patients were assessed through Day 28 for dose-limiting toxicities (DLTs) and response. A Bayesian approach was used for continuous monitoring of DLTs from Days 1-28. Treatment continued until GVHD progression, unacceptable toxicity, or withdrawal from the study. Acute GVHD was graded according to MN-CIBMTR criteria; adverse events (AEs) were graded according to NCICTCAE v 4.03. Results: Between January and June 2016, 31 patients (TN, n=14; SR, n= 17) were randomized. As of July 25, 2016, data were available from 30 patients who received an oral daily dose of 200 mg (n=14) or 300 mg (n=16) INCB039110 in combination with 2 mg/kg methylprednisolone (or equivalent dose of prednisone). The median durations of treatment were 60.8 days and 56.5 days for patients receiving a daily dose of 200 mg and 300 mg INCB039110, respectively. One DLT of Grade 3 thrombocytopenia was reported. The most frequently reported AEs included thrombocytopenia/platelet count decrease (26.7%), diarrhea (23.3%), peripheral edema (20%), fatigue (16.7%), and hyperglycemia (16.7%). Grade 3 or 4 AEs occurred in 77% of patients and with similar frequency across dose groups and included cytomegalovirus infections (n=3), gastrointestinal hemorrhage (n=3), and sepsis (n=3). Five patients had AEs leading to a fatal outcome, including multi-organ failure (n=2), sepsis (n=1), disease progression (n=1), and bibasilar atelectasis, cardiopulmonary arrest, and respiratory distress (n=1); none of the fatal events was attributed to INCB039110. Efficacy and PK evaluations are ongoing and will be updated at the time of presentation. Conclusion: The oral, selective JAK1 inhibitor INCB039110 can be given safely to steroid-naive or steroid-refractory aGVHD patients. The safety profile was generally consistent in both dose groups. Biomarker evaluation, PK, and cellular phenotyping studies are ongoing. The recommended phase 2 dose will be selected and reported based on PK studies and final safety data. Disclosures Schroeder: Incyte Corporation: Honoraria, Research Funding. Khoury:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding. Jagasia:Incyte Corporation: Research Funding; Therakos: Research Funding; Janssen: Research Funding. Ali:Incyte Corporation: Research Funding. Schiller:Incyte Corporation: Research Funding. Arbushites:Incyte Corporation: Employment, Equity Ownership. Delaite:Incyte Corporation: Employment, Equity Ownership. Yan:Incyte Corporation: Employment, Equity Ownership. Rhein:Incyte Corporation: Employment, Equity Ownership. Perales:Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte Corporation: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Chen:Incyte Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding. DiPersio:Incyte Corporation: Research Funding.

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Efficacy of Ruxolitinib By Baseline Spleen Volume in Patients with Polycythemia Vera Resistant to or Intolerant of Hydroxyurea

Blood ◽

10.1182/blood.v124.21.1840.1840 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1840-1840 ◽

Cited By ~ 1

Author(s):

Alessandro M. Vannucchi ◽

Srdan Verstovsek ◽

Mark M Jones ◽

Shui He ◽

Jingjin Li ◽

...

Keyword(s):

Logistic Regression ◽

Linear Regression ◽

Polycythemia Vera ◽

Board Of Directors ◽

Research Funding ◽

Spleen Volume ◽

Employment Equity ◽

Advisory Committees ◽

Equity Ownership ◽

Response Trial

Abstract Background : Polycythemia vera (PV) is a myeloproliferative neoplasm defined by erythrocytosis; patients may also have increased platelets and white blood cells as well as splenomegaly and disease-related symptoms. JAK/STAT activation is the primary driver of PV pathogenesis, in most cases resulting from the JAK2V617F mutation. The RESPONSE trial compared ruxolitinib (RUX) and best available therapy (BAT) in patients with PV and splenomegaly who were intolerant of or resistant to hydroxyurea (HU) according to modified European LeukemiaNet criteria. At the time of the primary analysis, RUX demonstrated superior improvements in hematocrit (HCT) control, symptom burden, and spleen volume compared with BAT. This post hoc analysis of RESPONSE was conducted to determine if treatment outcomes were influenced by baseline spleen volume. Methods : Patients with PV ≥18 years of age who were resistant to or intolerant of HU with palpable spleen (confirmed by MRI/CT to be ≥450 cm3) and phlebotomy requirement were randomized 1:1 to receive open-label RUX 10 mg BID or BAT. The primary endpoint was a composite that required a ≥35% reduction in spleen volume at Week 32 and hematocrit (HCT) control. HCT control was defined as lack of phlebotomy eligibility (based on HCT values) between Weeks 8–32 with no more than 1 phlebotomy eligibility between randomization and Week 8. A linear regression was conducted to determine the effect of baseline spleen volume on the percent change in spleen volume at Week 32. A logistic regression was conducted to determine the effect of baseline spleen volume on HCT control through Week 32. Spleen volume was measured by MRI at screening and Weeks 16 and 32. Hematocrit was assessed at screening, prerandomization, and every 2 weeks from Day 1 to Week 12, followed by every 4 weeks until Week 32. Results :The RESPONSE trial enrolled 222 patients (RUX, 110; BAT, 112). Median (range) spleen volume at baseline was 1195 cm3 (396–4631 cm3) in the RUX arm and 1322 cm3 (254–5147 cm3) in the BAT arm. Baseline median (range) spleen length by palpation was 7.0 cm (0.0–24.0 cm) in the RUX arm and 7.0 cm (0.0–25.0 cm) in the BAT arm. In the 24 weeks prior to screening, most patients in both arms had ≥2 phlebotomy procedures (RUX, 87%; BAT, 80%). There was no correlation between the percentage change in spleen volume at Week 32 and baseline spleen volume; linear regression showed no significant effect of baseline spleen volume on the percentage change in spleen volume at Week 32 (P=0.40). No significant effect of baseline spleen volume on HCT control through Week 32 was identified based on logistic regression analysis (P=0.37). Conclusion : In PV patients with inadequate response to or intolerant of HU, the degree of splenomegaly at baseline did not influence achievement of HCT control or reduction in spleen volume with RUX therapy. Disclosures Vannucchi: Novartis Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Off Label Use: Ruxolitinib is a JAK1/JAK2 inhibitor approved for the treatment of patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis, post polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis. Verstovsek:Incyte Corporation: Research Funding. Jones:Incyte Corporation: Employment, Equity Ownership. He:Incyte Corporation: Employment, Equity Ownership. Li:Novartis Pharmaceuticals: Employment, Equity Ownership. Habr:Novartis Pharmaceuticals: Employment, Equity Ownership. Kiladjian:Novartis Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

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A Phase 1b Study Investigating Carfilzomib Administered Once Weekly in Combination with Lenalidomide and Dexamethasone in Patients with Multiple Myeloma

Blood ◽

10.1182/blood.v128.22.3322.3322 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3322-3322

Author(s):

Noa Biran ◽

David S. Siegel ◽

Jesus G. Berdeja ◽

Edward Faber ◽

Lasika Seneviratne ◽

...

Keyword(s):

Multiple Myeloma ◽

Research Funding ◽

Response Rates ◽

The United States ◽

Median Number ◽

Employment Equity ◽

Dose Evaluation ◽

Phase 1B ◽

Equity Ownership ◽

Grade 3

Abstract Background: The combination of carfilzomib with lenalidomide and dexamethasone (KRd) is approved in the United States and the European Union (EU) for the treatment of patients with relapsed or refractory multiple myeloma (RRMM). Under these approvals, carfilzomib is administered twice weekly as a 10-minute intravenous (IV) infusion at a dose of 20/27 mg/m2. The phase 1/2 CHAMPION-1 study showed that once-weekly carfilzomib (20/70 mg/m2; 30-minute IV infusion) with dexamethasone was well tolerated and active in patients with RRMM (Berenson et al. Blood. 2016;127:3360−3368). We present initial results from the dose evaluation component of a phase 1b study (NCT02335983) assessing the safety and efficacy of once-weekly carfilzomib with lenalidomide and dexamethasone in patients with MM. Methods: This is an open-label, multicenter, dose-finding, phase 1b study.The primary objective of the study is to evaluate the safety and tolerability of a once-weekly KRd regimen. Secondary objectives included evaluation of the efficacy of a once-weekly KRd regimen. This study consists of 2 parts: a dose-evaluation component in patients with RRMM and a dose-expansion component in both RRMM and newly diagnosed MM (NDMM). Results from the ongoing dose-evaluation component in RRMM are presented. There were 2 planned dose cohorts in the dose-evaluation portion of the study: carfilzomib 56 mg/m2 KRd cohort (56 mg/m2) and carfilzomib 70 mg/m2 KRdcohort (70 mg/m2). All patients received carfilzomib (days 1, 8, and 15), lenalidomide 25 mg (days 1 - 21), and dexamethasone 40 mg (days 1, 8, 15 and 22) on a 28-day cycle (dexamethasone was not administered on day 22 for cycles 9+). Carfilzomib was administered as a 30-minute IV infusion: 20 mg/m2 on cycle 1 day 1 with escalation to the assigned dose level (56 or 70 mg/m2) thereafter. The protocol allowed 8 DLT-evaluable patients to be treated in the 56 mg/m2 and 70 mg/m2 cohorts. Response was assessed by investigators using International Myeloma Working Group Uniform Response Criteria. The data cutoff date for this analysis was June 23, 2016. Results: A total of 22 patients (56 mg/m2, n=10; 70 mg/m2, n=12) with a median age of 69 (range, 50-87) years were enrolled in the dose evaluation component of the study. The median number of prior regimens was 1 (range, 1 - 3) in both cohorts. There were no dose-limiting toxicities observed in any of the 15 dose-evaluable RRMM patients (56 mg/m2 cohort, n=8; 70 mg/m2 cohort, n=7). The median number of cycles started as of data cutoff was 9.5 (range, 3-15) in the 56 mg/m2 cohort and 6.0 (range, 2-9) in the 70 mg/m2 cohort. All patients experienced at least 1 treatment-emergent adverse event (AE). Grade ≥3 AEs occurring in ≥9% of patients, and any AE of interest are shown in Table 1. The only grade ≥3 AEs to occur in ≥2 patients (≥9%) were thrombocytopenia (56 mg/m2, n=2; 70 mg/m2, n=1), decreased neutrophil count (56 mg/m2, n=2; 70 mg/m2, n=1), anemia (56 mg/m2, n=2), and hypertension (56 mg/m2, n=1; 70 mg/m2, n=1). Although the numbers were small, there was no apparent difference in the incidence of dyspnea or hypertension between the 56 and 70 mg/m2 cohorts. Cardiac or renal failure of any grade was not reported at the time of the database snapshot in these patients with RRMM. Response rates after 4 cycles, as assessed by investigators, are shown in Table 2. Two patients in the 56 mg/m2 cohort did not complete 4 cycles: an 87-year old patient developed asymptomatic pulmonary hypertension (detected on a required echocardiogram study) and was taken off therapy; another patient withdrew consent. One patient in the 70 mg/m2 cohort had a partial response after cycle 1 but was found to have progressive disease in cycle 3 (listed as did not complete 4 cycles in Table 2). After 4 cycles, the response rates (investigator assessed), were 70% and 75% in the 56 and 70 mg/m2 cohorts (response assessment for 2 patients in the 70 mg/m2 cohort was missing at the time of the data cutoff). Conclusions: These results demonstrate that carfilzomib administered in a convenient once-weekly schedule in combination with lenalidomide and dexamethasone in patients with RRMM is safe with promising efficacy. The 70 mg/m2 dosing was selected for dose-expansion cohorts in RRMM and NDMM. An update on the expansion cohorts will be presented at the meeting. Disclosures Biran: Onyx: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau. Siegel:Novartis: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Merck: Honoraria; BMS: Honoraria, Speakers Bureau; Celgene: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau. Berdeja:Abbvie, Acetylon, Amgen, Bluebird, BMS, Calithera, Celgene, Constellation, Curis, Epizyme, Janssen, Karyopharm, Kesios, Novartis, Onyx, Takeda, Tragara: Research Funding. Faber:Celgene: Speakers Bureau; Cardinal Health: Honoraria; Gilead: Consultancy, Honoraria. Seneviratne:Novartis Pharmaceuticals: Speakers Bureau. Alsina:Onyx: Speakers Bureau; Millenium Pharmaceuticals: Research Funding; Novartis: Research Funding; Signal Genetics: Consultancy; Onyx: Consultancy. Bensinger:Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Honoraria, Research Funding, Speakers Bureau. Kimball:Amgen Inc.: Employment, Equity Ownership. Zhou:Amgen Inc.: Employment, Equity Ownership. Landgren:BMS: Honoraria; Takeda: Honoraria; Novartis: Honoraria; Amgen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding.

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Treatment Patterns Among Adults with Newly Diagnosed Primary Immune Thrombocytopenia in the United States

Blood ◽

10.1182/blood-2018-99-117252 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 497-497

Author(s):

Karynsa Cetin ◽

Leah J McGrath ◽

Robert Overman ◽

Diane Reams ◽

Anjali Sharma ◽

...

Keyword(s):

Cumulative Incidence ◽

Research Funding ◽

Rescue Therapy ◽

The United States ◽

Advisory Board ◽

Oral Steroid ◽

Newly Diagnosed ◽

Employment Equity ◽

The Us ◽

Equity Ownership

Abstract Introduction: Immune thrombocytopenia (ITP) is a rare platelet disorder that can lead to an increased tendency to bleed. Recommended first-line therapies include corticosteroids, intravenous immunoglobulin (IVIg) and intravenous (IV) anti-D. An estimated two-thirds of adult patients with ITP will develop persistent or chronic disease (ITP lasting 3-12 months or >12 months, respectively). Several evidence-based options for second-line treatment exist, but no randomized trials have directly compared one therapy to another. Patterns of treatment in routine clinical practice therefore vary. There is a paucity of data on current real-world treatment dynamics in ITP, and such data could help identify gaps in care and inform future studies of real-world comparative effectiveness and safety. We described the types of treatments administered following an ITP diagnosis, as well as the subsequent occurrence of bleeding and requirement for rescue therapy among adults being managed in routine practice in the United States (US). Methods: We used electronic health record data from hematology clinics across the US (Flatiron Health, Inc.) linked to MarketScan® employer-based and Medicare Supplemental administrative health insurance claims databases (Truven Health Analytics, Inc.). We included patients aged 18 years or older with a new ITP diagnosis from January 1, 2011 through June 30, 2016, continuous enrollment in MarketScan prior to diagnosis, and no previous diagnosis of a secondary cause of thrombocytopenia. The cumulative incidence of each ITP treatment after diagnosis was estimated using competing risk models to account for deaths occurring before initiation. Estimates were provided specifically for 90 days and 1 year following diagnosis to describe treatment uptake in the newly diagnosed and persistent phases, respectively. The incidence of bleeding events and rescue therapy was quantified after the start of the more prevalent second-line therapies: rituximab, splenectomy, and thrombopoietin receptor agonists (TPO RAs) - eltrombopag and romiplostim. Rescue therapies (those that rapidly increase platelet counts in the setting of severe thrombocytopenia or active bleeding) included IV anti-D, IVIg, IV steroids, and platelet transfusions. Results: Among the cohort of 447 adults diagnosed with primary ITP, 47% were male, 61% were white, 32% were 65 years or older, and the median lowest platelet count in the 60 days prior to diagnosis was 85x109/L (IQR: 39, 125). Use of each ITP therapy by 90 days and 12 months post-diagnosis are provided in the Table. Oral corticosteroids were the most commonly used; the cumulative incidence of initiation was 41% by 90 days and 50% by 1 year following ITP diagnosis. IV steroids and rituximab were the next most frequently used medications (16% and 11% at 90 days; and 26% and 16% by 1 year, respectively). The cumulative incidence of the TPO RAs, eltrombopag and romiplostim, by 90 days was 3% and 7%, respectively, and by 1 year was 5% and 9%, respectively. Splenectomy was relatively rare (<4% by 1 year) as was use of all other non-rescue ITP medications (≤1% by 1 year). At 180 days post-ITP treatment initiation, rituximab initiators (N = 84) had a slightly lower incidence of bleeding overall (12% [6, 20]) than the other treatment groups (17% [6, 33] among 31 eltrombopag initiators; 19% [9, 31] among 49 romiplostim initiators; and 19% [6, 38] among 21 splenectomized patients). However, rituximab initiators had the highest cumulative incidence of rescue therapy use (48% [36, 58] compared with 29% [14, 46] for eltrombopag, 26% [14, 39] for romiplostim, and 19% [6, 39] for splenectomized patients). Subsequent oral steroid use was less frequent among TPO RA initiators than rituximab initiators or patients who underwent splenectomy. Conclusions: In this descriptive study of patients with primary ITP receiving care in the US, oral steroids were the most commonly used medication after diagnosis, reflecting their continued role as a frontline therapy. By 1 year after diagnosis, approximately 15% received rituximab, nearly 10% received romiplostim, and 5% received eltrombopag. Splenectomy was less common. Among the medical treatments, although bleeding risk overall appeared lowest in rituximab patients, oral steroid and rescue therapy use were lowest among the patients who initiated TPO RAs. Table. Table. Disclosures Cetin: Amgen Inc: Employment, Equity Ownership. Sharma:Amgen: Employment, Equity Ownership. Brookhart:Amgen Inc: Consultancy, Research Funding; NoviSci: Equity Ownership; Union Chimique Belge: Consultancy; GlaxoSmithKline: Consultancy; Merck: Consultancy; Genentech: Consultancy; TargetPharma: Consultancy; RxAnte: Consultancy; AstraZeneca: Research Funding. Altomare:Genentech: Consultancy; Ipsen: Other: Advisory Board Member; Amgen: Consultancy; Celgene: Other: Advisory Board Member; Novartis: Consultancy; Bayer: Consultancy; Incyte: Consultancy. Wasser:Amgen Inc: Consultancy; Novartis: Consultancy; Becton Dickinson: Equity Ownership; Abbott Labs: Equity Ownership; Biogen: Equity Ownership; Allergan: Equity Ownership; Eli Lilly: Equity Ownership; Incyte: Research Funding; Merck: Equity Ownership, Research Funding; Pfizer: Equity Ownership, Research Funding; Guardant: Research Funding.

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Real-World Analysis of Ruxolitinib Treatment Patterns and Outcomes Among Patients with Myelofibrosis

Blood ◽

10.1182/blood-2019-124651 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4750-4750 ◽

Cited By ~ 1

Author(s):

Tanya Burton ◽

Kejal Parikh ◽

Manish Patel ◽

Kevin Sundquist ◽

Lincy S. Lal ◽

...

Keyword(s):

Health Plan ◽

Research Funding ◽

Index Date ◽

Myeloproliferative Neoplasm ◽

Treatment Patterns ◽

Systemic Steroid ◽

Administrative Claims ◽

Employment Equity ◽

Oncology Research ◽

Equity Ownership

Background: Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by bone marrow fibrosis, splenomegaly, cytopenias, and poor survival. Ruxolitinib (RUX) is the only approved treatment for Intermediate or High-risk MF. In a previous study, we have shown almost 1 in 3 patients initiating RUX had dose modifications during the first 3 months of treatment (Burton T et al. HemaSphere 2019). The objective of this study was to assess RUX treatment patterns among patients with MF. Methods: This retrospective analysis used administrative claims data from a large US health plan to identify adults (aged ≥ 18 years) with ≥ 1 claim for RUX and ≥ 2 non-diagnostic medical claims for primary (International Classification of Diseases [ICD] 9th or 10th Revision [9/10]: 238.76, D47.4) or secondary MF (ICD-9/10: 289.83, D75.81) from January 1, 2012 to June 30, 2018. The first RUX claim on or after the first MF claim defined the index date. Included patients were continuously enrolled in a commercial or Medicare Advantage health plan for 3 months before the index date (pre-index period) and 6 months on or after the index date (post-index period). Clinical characteristics, MF-related treatments, health care resource utilization (HCRU), and costs were assessed during the pre- and post-index periods. Costs were adjusted to 2018 US dollars using the medical component of the Consumer Price Index. Cohorts were created based on the maximum (max) RUX daily dose observed during the 6-month post-index period: suboptimal max < 30 mg/day (SUB); and optimal max ≥ 30 mg/day (OPT). All variables were analyzed descriptively. Results: Among 495 eligible patients, mean (SD) age was 69.4 (10.3) years; 54.1% were male; and 25% had a primary MF diagnosis code. Median initial RUX dose was 30 mg/day and patients continued with this dose for a mean (SD) of 70.0 (45.8) days. RUX dose was modified for 19.4% of patients during the 6-month post-index period, and the distribution of max RUX daily doses was: < 15 mg (13.7%), 15-29 mg (24.9%), 30-40 mg (55.8%), and > 40 mg (5.7%). Two groups based on max RUX dosing were further analyzed: 191 (38.6%) in the SUB cohort (< 30 mg), and 304 (61.4%) in the OPT cohort (≥ 30 mg). Patients in the SUB cohort were older than patients in the OPT cohort (SUB: mean 70.8 [SD 10.1] years; OPT: mean 68.5 [SD 10.3] years; P = 0.013), but the mean Charlson Comorbidity Index scores did not differ (SUB: mean 1.6 [SD 1.8]; OPT: mean 1.5 [SD 1.8]; P = 0.601). Rates of anemia were higher at baseline for the SUB cohort than the OPT cohort (SUB: 64.9%; OPT: 53%; P = 0.009). During the 6-month post-index period, compared with patients in the OPT cohort, patients in the SUB cohort had a higher proportion of thrombocytopenia (SUB: 31.4%; OPT: 22.7%; P = 0.03). Nearly half (45.5%) the sample used a supportive agent such as an androgen, systemic steroid, or erythropoiesis-stimulating agent during the post-index period (SUB: 48.2%; OPT: 43.8%; P = 0.34). With respect to HCRU and costs, the SUB cohort had a higher proportion of emergency department (ED) visits than the OPT cohort during baseline (SUB: 31.4%; OPT: 23.4%; P = 0.048); and baseline total mean (SD) all-cause costs were USD 18,079 (21,876) overall, USD 18,908 (24,411) for the SUB cohort, and USD 17,559 (20,145) for the OPT cohort (P = 0.523). During the 6-month follow-up period, 31.1% of patients had ≥ 1 ED visit (SUB: 35.1%; OPT: 28.6%; P = 0.131), 22.8% had ≥ 1 inpatient (IP) hospitalization (SUB: 24.6%; OPT: 21.7%; P = 0.455), and total mean (SD) all-cause costs were USD 94,498 (97,391) overall (SUB: USD 93,289 [115,418]; OPT: USD 95,258 [84,315]; P = 0.839). Conclusion: In this study, patients with MF treated with RUX experienced significant disease burden and high costs, regardless of dose. Both anemia and thrombocytopenia were observed along with nearly half of patients using a supportive agent. Given the large proportion of patients with a dose adjustment, suboptimal dosing, and an IP hospitalization, there continues to be a need for additional therapeutic options for patients with MF. Disclosures Parikh: Celgene Corporation: Employment, Equity Ownership. Patel:Celgene Corporation: Employment, Equity Ownership. Sundquist:Optum: Employment, Equity Ownership. Lal:Optum: Employment. Copher:Celgene Corporation: Employment. Gerds:Roche: Research Funding; Incyte: Consultancy, Research Funding; Sierra Oncology: Research Funding; CTI Biopharma: Consultancy, Research Funding; Imago Biosciences: Research Funding; Celgene Corporation: Consultancy, Research Funding; Pfizer: Consultancy.

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Real-World Treatment Patterns and Overall Survival Among Medicare Fee-for-Service Beneficiaries Newly Diagnosed with Peripheral T-Cell Lymphoma

Blood ◽

10.1182/blood-2019-130973 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3492-3492

Author(s):

Anne Shah ◽

Allison Petrilla ◽

Mayvis Rebeira ◽

Joseph Feliciano ◽

Thomas W. LeBlanc ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Brentuximab Vedotin ◽

Treatment Patterns ◽

Fee For Service ◽

Newly Diagnosed ◽

Medicare Beneficiaries ◽

Employment Equity ◽

Advisory Committees ◽

Equity Ownership

Background: Peripheral T-cell lymphomas (PTCL) are a rare and heterogeneous group of lymphoid malignancies characterized by a clinically aggressive course with poor prognosis. A majority of PTCL patients are ≥60 years of age and typically present with advanced stage disease and multiple comorbidities. There remains no consensus standard of care for patients with most PTCL subtypes. Multi-agent chemotherapy, consisting of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or CHOP with etoposide (CHOEP), are guideline recommended options for nodal subtypes. Limited contemporary real-world data exist on the treatment patterns and overall survival (OS) of PTCL patients treated with CHOP or non-CHOP regimens in the United States before the FDA approval of brentuximab vedotin in combination with chemotherapy in November 2018 based on the ECHELON-2 trial. Objective: To evaluate treatment patterns and OS prior to the approval of brentuximab vedotin among Medicare Fee-for-Service (FFS) beneficiaries newly diagnosed with PTCL. Methods: The 100% sample of Medicare FFS claims (Parts A/B/D) was used to identify patients aged ≥65 years with ≥1 inpatient or ≥2 distinct outpatient diagnosis claims for PTCL (index event) from January 2011 to December 2017. Patients were required to have a least 6 months prior and 12 months post-index continuous Medicare enrollment, and were followed until disenrollment, death, or the end of the study period, whichever occurred first. OS, defined as the time from initial episode or treatment start date to the validated date of death, was measured using the Kaplan-Meier method; patients without a death date were assumed to be alive at the time of analysis and were censored. Results: A total of 2551 Medicare FFS beneficiaries with a PTCL diagnosis met study criteria and were included for analysis. The majority of patients were white (86.9%), over half were male (52.9%), and mean age was 75 years. Patients had multiple comorbidities at diagnosis (Charlson Comorbidity Index (CCI) score 4.47), including hypertension (77.3%), diabetes (32.9%), and chronic obstructive pulmonary disease (28.1%). Among the 2551 patients in the study cohort, 62.4% (n=1593 of 2551) received at least one identifiable drug regimen; 25.5% of treated patients received CHOP (n=407), 3.1% CHOEP (n=50) and 71.2% (n=1134) other regimens. Of patients treated with other regimens, 37.7% (n=427) received steroids only, 22.4% (n=254) steroids with unidentifiable chemotherapy, 6.9% (n=78) cyclophosphamide, 6.2% (n=70) methotrexate, 4.6% (n=52) brentuximab vedotin, 3.6% (n=41) bendamustine, 3.5% (n=40) romidepsin, and 15.2% (n=172) other therapy combinations. Among patients who were treated with CHOP, 16.6% (n=66) received an identifiable second line of therapy (LoT), 48.7% (n=194) an unidentifiable second LoT, and the remainder (34.7%, n=138) had no evidence of further anti-cancer treatment. The median time from CHOP initiation to a subsequent LoT was 5.6 months. The mean baseline CCI score for patients treated with CHOP was 4.33 (±2.93) compared with 4.76 (±2.97) for patients treated with other therapies (p=0.0118). In patients receiving an identifiable first LoT, median OS among CHOP and non-CHOP recipients was 4.8 years (95% CI 3.0-6.1) and 4.4 years (95% CI 3.0-4.9), respectively (Table). The 5-year OS estimate was 49% in patients receiving CHOP compared with 46% for non-CHOP recipients. Conclusions: Fewer than 30% of Medicare beneficiaries newly diagnosed with PTCL were treated with intensive chemotherapy as first LoT. Acknowledging a possible selection bias for more fit PTCL patients receiving CHOP, this group had increased OS compared with patients receiving non-CHOP therapy. However, the 5-year OS across all cohorts was less than 50%. New therapies such as brentuximab vedotin may fill the need for PTCL Medicare beneficiaries who may not be able to tolerate CHOP or CHOP-based regimens. Disclosures Shah: Avalere Health, An Inovalon Company: Employment. Petrilla:Avalere Health, An Inovalon Company: Employment. Rebeira:Seattle Genetics: Employment. Feliciano:Seattle Genetics: Employment, Equity Ownership. LeBlanc:Astra Zeneca: Consultancy, Research Funding; Duke University: Research Funding; Jazz Pharmaceuticals: Research Funding; Daiichi-Sankyo: Membership on an entity's Board of Directors or advisory committees; Helsinn: Consultancy; Agios: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; NINR/NIH: Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Otsuka: Consultancy, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Research Funding; CareVive: Consultancy; Celgene: Honoraria; Flatiron: Consultancy; American Cancer Society: Research Funding; Heron: Membership on an entity's Board of Directors or advisory committees; Medtronic: Membership on an entity's Board of Directors or advisory committees; Pfizer Inc: Consultancy. Lisano:Seattle Genetics, Inc.: Employment, Equity Ownership.

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