MPN Experimental Assessment of Symptoms by Utilizing Repetitive - - PowerPoint PPT Presentation

MPN Experimental Assessment of Symptoms by Utilizing Repetitive Evaluation (MEASURE) Trial

Myeloproliferative Neoplasm Quality of Life (MPN-QOL) Study Group

Allison H. Smith, MD, MPH Hematology/Oncology Fellow Norris Cotton Cancer Center Dartmouth-Hitchcock Medical Center

Myeloproliferative Neoplasms (MPN)

Polycythemia vera (PV) Essential thrombocythemia (ET) Myelofibrosis (MF)

• Gene mutations:
• Janus kinase 2 (JAK2)
• Calreticulin (CALR)
• Thrombopoietin receptor (MPL)
• Hematopoietic stem

cell disorders

• Clonal proliferation of

1+ myeloid cell lines

Clinical Features

• Polycythemia or anemia
• Leukocytosis
• Thrombocytosis
• Hepatosplenomegaly
• Risk of thrombotic and thromboembolic events
• Risk of bleeding
• Risk of progression to MF, MDS, or AML
• Increased mortality

Symptom Burden

• 90% of patients experience MPN-related symptoms
• Most common and severe = fatigue
• Most patients report decline in quality of life
• Impairment in work functioning and activity level
• MF patients often have highest symptom burden and

lowest quality of life

Harrison et al. Ann Hematol 2017;96(10):1653-1665

Common MPN Symptoms

✓ Fatigue ✓ Early satiety ✓ Anorexia ✓ Pruritis ✓ Bone pain ✓ Night sweats ✓ Cachexia/weight loss ✓ Abdominal pain ✓ Nausea ✓ Fever ✓ Weakness ✓ Mood changes ✓ Sleep disturbance ✓ Cognitive impairment

Treatment Approaches

• Pharmacologic options
• Cytoreductive therapy – hydroxyurea, anagrelide, pegylated

interferon, busulfan

• JAK1/2 inhibition – ruxolitinib
• COMFORT I trial: reduction in spleen size, improvement in

symptoms (abdominal pain, bone pain, night sweats, pruritis)

• Antiplatelet – aspirin, clopidogrel
• Anticoagulation – warfarin
• Phlebotomy
• Stem cell transplantation

Verstovsek et al. Blood 2012;120(6):1202-1209

Background

• Outcome studies have historically focused on

hematologic improvement and survival benefit

• Few prospective studies have evaluated patient-

reported symptoms and quality of life outcomes

• MEASURE trial aims to quantify objectively

symptomatic response to standard therapies

• Interim results presented:
• 340 patients enrolled
• 270 patients have completed both study visits

MEASURE Trial

• MPN Experimental Assessment of Symptoms by

Utilizing Repetitive Evaluation (MEASURE) trial

• Prospective international cohort study
• Evaluates changes in target symptoms:
• Common MPN symptoms
• Impacts on functioning in various domains
• Global quality of life measures
• Non-experimental medical therapy and/or phlebotomy
• Anticipated 480 ET, PV, and MF patients

Study Methods

• Study visits:

1) At enrollment 2) Three to six months after enrollment

• Patients complete survey instruments:
• MPN-SAF TSS – seven consecutive days
• EORTC QLQ-C30
• MDASI
• Hematology physicians report:
• Patient demographics
• Laboratory data
• Clinical information

Myeloproliferative Neoplasm Symptom Assessment Form - Total Symptom Score (MPN-SAF TSS)

European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire, Core-30 (EORTC QLQ-C30)

M.D. Anderson Symptom Inventory (MDASI)

Results: Demographics

• Interim results: 340 patients enrolled (of target 480)
• 270 have completed both study visits
• Average 140 days between visits
• 51% male, 49% female

Results: Clinical Data

• Mutational analysis (not required):
• 77% have JAK2 V617F
• 3% have MPL W515
• <1% have JAK2 exon 12, CALR, TET2, ASXL1, EZH2
• Clinical features:
• History of splenectomy

2%

• History of thrombosis

15%

• History of hemorrhage

4%

• Required transfusion

4%

Results: Therapies

• Most common therapies received prior to enrollment:
• Aspirin (34%)
• Phlebotomy (15%)
• Hydroxyurea (14%)
• Anticoagulation/warfarin (6%)
• Most common current MPN therapies:
• Hydroxyurea (67%)
• Aspirin (24%)
• Phlebotomy (9%)
• Ruxolitinib (8%)

Results: MPN-SAF TSS

• Significant decrease in weight loss
• Significant increase in poor quality of life
• No improvements in other symptoms
• Cumulative MPN-SAF TSS score remained stable at 24.4

P = 0.0046 P = 0.0370

Results: EORTC QLQ-C30

No significant improvements in any of 5 domains of functioning

Results: MDASI

No change in symptom severity or symptom distress scores

Discussion

• MPNs are associated with burdensome symptoms that

significantly compromise quality of life

• To date, no prospective studies have quantified symptomatic

response to standard-of-care treatments

• Interim results from MEASURE trial suggest that standard

treatments have limited impact on patient symptomatology

• No improvements in overall quality of life
• Congruent findings among all 3 survey instruments
• Relatively low proportion of patients in this cohort treated with

ruxolitinib

• Shown previously to improve symptom burden
• May have impacted symptom responses seen in the group as whole

Future Directions

• Complete study enrollment and data analysis
• Symptom burden and treatment impact by MPN type
• Impact of ruxolitinib therapy on QOL and symptoms
• Correlation between hematologic outcomes and patient

reported outcomes

• Physician assessment of symptom burden

Acknowledgments

• NNECOS
• Fellowship faculty at DHMC
• Program director: Mary Chamberlin, MD
• Research mentors at Mayo Clinic Arizona
• Ruben Mesa, MD
• Holly Geyer, MD
• Study staff at MEASURE trial international sites
• Our study subjects

❖ Mayo Clinic, Phoenix, AZ, USA ❖ UT Health, San Antonio, TX, USA ❖ Azienda Ospedaliera-Universitaria Careggi, Florence, Italy ❖ Hospital La Paz, Madrid, Spain ❖ Roskilde University Hospital, Roskilde, Denmark ❖ NU Hospital Organization, Uddevalla, Sweden ❖ Institution for Medical Sciences, Uppsala, Sweden ❖ Hospital Organization, Uddavella, Sweden ❖ Uddevalla Sjukhus, Uddavella, Sweden ❖ Royal Adelaide Hospital, Adelaide, Australia ❖ FUNDALEU, Buenos Aires, Argentina ❖ Hôpitaux de l'Université Catholique, Lille, France ❖ St Vincent's Hospital, Fitzroy, Australia ❖ Goodheart Instiutie Rotterdam, Amsterdam, Netherlands NHS Foundation Trust: ❖ Guy's & St Thomas, London, UK ❖ Heart of England, Birmingham, UK ❖ University of Nottingham, Nottingham, UK ❖ Royal Marsden Hospital, London, UK ❖ Belfast City Hospital, Belfast, UK ❖ Calderdale & Huddersfield Royal Infirmary, Huddersfield, UK ❖ Salisbury Healthcare, Salisbury, UK ❖ Hampshire Hospitals, Southampton, UK ❖ Mid Yorkshire Hospitals, Wakefield, UK ❖ St James's University Hospital, Leeds, UK ❖ Royal Free Hospital, London, UK ❖ Guy's Hospital, London, UK

Study Sites

Thank you!