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) • Hematopoietic stem cell disorders • Clonal proliferation of 1+ myeloid cell lines • Gene mutations: • Janus kinase 2 ( JAK2 ) • Calreticulin ( CALR ) • Thrombopoietin receptor ( MPL )

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 ✓ Abdominal pain ✓ Early satiety ✓ Nausea ✓ Anorexia ✓ Fever ✓ Pruritis ✓ Weakness ✓ Bone pain ✓ Mood changes ✓ Night sweats ✓ Sleep disturbance ✓ Cachexia/weight loss ✓ 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 = 0.0370 P = 0.0046

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

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

Thank you!