Differences in treatment goals and perception of symptom burden between patients with myeloproliferative neoplasms (MPNs) and hematologists/oncologists in the United States: Findings from the MPN Landmark survey

Abstract Background: Patients with myeloproliferative neoplasms (MPNs), including myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET), experience a high symptom burden that may compromise daily functioning and quality of life. The objective of this analysis was to evaluate income loss associated with disease-related employment changes among patients with MPNs in the United States. Methods: The Living with MPN survey was completed online by adult patients (aged 18-70 years) with MF, PV, or ET in the United States between April and November of 2016. Respondents employed at the time of MPN diagnosis were asked questions about disease-related changes in employment status and salaries occurring between diagnosis and the year of survey (2016). In addition, details related to patient demographics, MPN diagnosis, and MPN-related symptoms were collected. Cumulative income losses as a result of disease-related employment changes up to the time of the survey were calculated based on the timing of employment changes and salaries, which were reported in nominal dollars. Results: Of the 904 survey respondents, 592 (65%) were employed at the time of MPN diagnosis. Among those employed, mean age was 54.0 years, 70.6% were female, and 72.3% were married or had domestic partners at the time of survey. The average duration of disease was 6.1 years (MF, 4.6; PV, 6.9; ET, 6.3). Approximately half (50.5%) of the employed respondents experienced at least one change in employment status because of their diagnosis. Employment status changes and associated impact on income in patients with MPNs was greatest for those who took early retirement, medical disability leave, or left a job due to their disease ($419,610, $169,048, $168,245, respectively). Respondents who changed from full- to part-time employment, reduced hours, or were reassigned to a lower-paying job because of their disease also reported income losses ($79,492, $47,104, $51,872, respectively; Table). Among respondents who were 45-64 years old at the time of the survey (n=383), 18.8% reported retiring early as a result of their disease. In comparison, according to nationally representative data from the Medical Expenditures Panel Survey (MEPS), only 7.8% of individuals aged 45-64 years in excellent or very good health and 9.2% of individuals in poor health reported being retired (longitudinal data set 2014-2015). Moreover, 30.5% (117/383) of respondents aged 45-64 years in the Living with MPN survey reported leaving a job as a result of their disease. In comparison, 5.5% of MEPS individuals aged 45-64 years in excellent or very good health and 16.4% of individuals in poor health were working at the start of 2014 but not by the end of 2015. Conclusions: About half of employed patients living with MPNs experienced a variety of employment changes as a result of their disease, which in turn had a considerable impact on income. The most frequently reported disease-related employment change was leaving a job, followed by medical disability leave, reduced hours, early retirement, switching from full-time to part-time, and being reassigned to a lower-paying job. Patients 45-64 years old with MPNs were more than twice as likely to have left a job or retired early compared with an age-matched US general population cohort. On average, the foregone income due to disease-related employment changes was greatest for early retirees ($419,610), followed by those who went on medical disability leave ($169,048), and left a job ($168,245). Early, effective management of MPNs and associated symptoms may help patients avoid these disease-related changes to their employment status and the subsequent economic and financial impact. Disclosures Condliffe: Incyte Corporation: Consultancy. Yu:Incyte Corporation: Employment, Equity Ownership. Paranagama:Incyte: Employment, Equity Ownership. Parasuraman:Incyte: Employment, Equity Ownership.

Download Full-text

Challenges and solutions in the design and execution of the PROSPECT Phase II/III neoadjuvant rectal cancer trial (NCCTG N1048/Alliance)

Clinical Trials ◽

10.1177/1740774518824539 ◽

2019 ◽

Vol 16 (2) ◽

pp. 165-175 ◽

Cited By ~ 12

Author(s):

Deborah Schrag ◽

Martin Weiser ◽

Leonard Saltz ◽

Harvey Mamon ◽

Marc Gollub ◽

...

Keyword(s):

United States ◽

Rectal Cancer ◽

Neoadjuvant Chemotherapy ◽

Phase Ii ◽

Locally Advanced ◽

Symptom Burden ◽

The United States ◽

Distant Recurrence ◽

Neoadjuvant Chemoradiation ◽

Eligibility Criteria

Background More than half of the 40,000 incident rectal cancer patients in the United States each year are diagnosed at clinical stage II and III (locally advanced stage). For this group, high rates of cure can be achieved with the combination of pelvic radiation and sensitizing 5-fluorouracil (chemoradiation), surgery and chemotherapy, but treatment is long, arduous and toxicities are substantial. The PROSPECT trial (N1048, NCT01515787) was designed to determine whether neoadjuvant chemotherapy with 5-fluorouracil and oxaliplatin (FOLFOX) could be used as an alternative to neoadjuvant chemoradiation without compromising treatment outcomes and to spare these patients excess toxicity. The statistical design balanced the twin co-primary goals of achieving low local and distant recurrence rates. Study design features contended with the need for stringent safeguards given limited phase II data, the need for straightforward criteria to facilitate both accrual and protocol fidelity and the importance of patients’ perspectives on symptom burden and treatment toxicity. Methods PROSPECT is an ongoing multi-site two-group seamless phase II/III randomized trial comparing standard neoadjuvant chemoradiation versus neoadjuvant chemotherapy with selective use of chemoradiation for patients with locally advanced rectal cancer. Challenges addressed in the design and conduct of PROSPECT have included the following: (1) setting safety thresholds given limited single-center phase II data, (2) establishing workable eligibility criteria, (3) balancing competing time to local and distant recurrence as co-primary endpoints and (4) obtaining reliable and complete data for patients’ symptom burden. The design and implementation challenges, choices, modifications and their implications for the design of future national cooperative group clinical trials are presented. Results PROSPECT incorporated stringent thresholds for both complete surgical resection (R0) and the time to local recurrence as early stopping rules. When predetermined stopping criteria were not met after evaluation of the first 366 participants in the randomized phase II, the study transitioned seamlessly to phase III with cumulative accrual of over 1000 participants. Eligibility criteria stipulating rectal tumor location based on distance from the anal verge were unworkable, and the protocol was amended to a more pragmatic approach that assigned surgeons with primary responsibility for determining eligibility. Central radiology review was feasible and in some cases prompted discontinuation of protocol treatment. Participation in toxicity reporting using the National Cancer Institute’s Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events was uniformly high and was well accepted by participants from over 200 sites in the United States, Canada and Switzerland. Conclusion The strategies used to overcome these obstacles may inform the design of other studies that involve multi-modality treatment interventions, particularly trials where implementation of consistent criteria for eligibility and outcomes across hundreds of practice settings is necessary.

Download Full-text

Symptom Burden and Blood Counts in Patients With Polycythemia Vera in the United States: An Analysis From the REVEAL Study

Clinical Lymphoma Myeloma & Leukemia ◽

10.1016/j.clml.2019.06.001 ◽

2019 ◽

Vol 19 (9) ◽

pp. 579-584.e1

Author(s):

Michael R. Grunwald ◽

John M. Burke ◽

David J. Kuter ◽

Aaron T. Gerds ◽

Brady Stein ◽

...

Keyword(s):

United States ◽

Polycythemia Vera ◽

Symptom Burden ◽

The United States ◽

Reveal Study

Download Full-text

Potential Gains in Life Expectancy Associated with Achieving Treatment Goals in People with Type 2 Diabetes in the United States

SSRN Electronic Journal ◽

10.2139/ssrn.3923436 ◽

2021 ◽

Author(s):

Hamed Kianmehr ◽

Ping Zhang ◽

Jing Luo ◽

Jingchuan Guo ◽

Meda E. Pavkov ◽

...

Keyword(s):

United States ◽

Type 2 Diabetes ◽

Life Expectancy ◽

The United States ◽

Treatment Goals

Download Full-text

Symptom Burden of Irritable Bowel Syndrome With Constipation Among a Sample of Commercially-Insured Patients in the United States

The American Journal of Gastroenterology ◽

10.14309/00000434-201510001-01757 ◽

2015 ◽

Vol 110 ◽

pp. S745

Author(s):

Jessica L. Buono ◽

Qian Cai ◽

William M. Spalding ◽

Judith J. Stephenson ◽

Hiangkiat Tan ◽

...

Keyword(s):

United States ◽

Irritable Bowel Syndrome ◽

Symptom Burden ◽

The United States ◽

Irritable Bowel ◽

Insured Patients

Download Full-text

Novel therapeutics in myeloproliferative neoplasms

Journal of Hematology & Oncology ◽

10.1186/s13045-020-00995-y ◽

2020 ◽

Vol 13 (1) ◽

Author(s):

Sangeetha Venugopal ◽

John Mascarenhas

Keyword(s):

Risk Mitigation ◽

Clinical Investigation ◽

Myeloproliferative Neoplasms ◽

Management Strategies ◽

Philadelphia Chromosome ◽

Symptom Burden ◽

The United States ◽

Red Blood Cell Transfusion ◽

Hematopoietic Stem ◽

Transfusion Requirements

AbstractHyperactive signaling of the Janus-Associated Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) pathway is central to the pathogenesis of Philadelphia-chromosome-negative myeloproliferative neoplasms (MPN), i.e., polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) which are characterized by inherent biological and clinical heterogeneity. Patients with MPNs suffer from substantial symptom burden and curtailed longevity due to thrombohemorrhagic complications or progression to myelofibrosis or acute myeloid leukemia. Therefore, the management strategies focus on thrombosis risk mitigation in PV/ET, alleviation of symptom burden and improvement in cytopenias and red blood cell transfusion requirements, and disease course alteration in PMF. The United States Food and Drug Administration’s (USFDA) approval of two JAK inhibitors (ruxolitinib, fedratinib) has transformed the therapeutic landscape of MPNs in assuaging the need for frequent therapeutic phlebotomy (PV) and reduction in spleen and symptom burden (PV and PMF). Despite improving biological understanding of these complex clonal hematopoietic stem/progenitor cell neoplasms, none of the currently available therapies appear to modify the proclivity of the disease per se, thereby remaining an urgent unmet clinical need and an ongoing area of intense clinical investigation. This review will highlight the evolving targeted therapeutic agents that are in early- and late-stage MPN clinical development.

Download Full-text