How to monitor MPN patients

Transcription

1 How to monitor MPN patients

2 MPN carries significant burden and risk Transformation to MF or AML 1 Neurological complications 2 MPN-associated general symptoms (eg, pruritus, fatigue) 3 Microvascular symptoms (eg, headache or visual disturbances) 1 Macrovascular and CV events 1 Splenomegaly 4 AML=acute myeloid leukaemia; CV=cardiovascular; MF=myelofibrosis; MPN=myeloproliferative neoplasms; PV=polycythaemia vera. 1. Landolfi R, et al. Intern Emerg Med. 2010;5: doi /s Prchal JT, et al. Polycythemia vera. In: Kaushansky K, et al. Williams Hematology. 8th ed. New York: McGraw-Hill; Mesa RA, et al. Cancer. 2007;109(1): Swerdlow SH, et al, eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon, France: IARC;

3 Quality of life is an overall assessment of a person's well-being Quality of life assessment may include physical, emotional, and social dimensions, as well as self-perceived health status Centers for Disease Control and Prevention. Measuring Healthy Days. Atlanta, Georgia: CDC, November

4 Treatment recommendations for ET and PV are based on risk of thrombosis Currently recommended treatments per European LeukemiaNet (ELN) guidelines: Low Risk Age <60 years and no history of thrombosis Low-dose aspirin Phlebotomy for PV High Risk Age 60 years or history of thrombosis Low-dose aspirin Phlebotomy According to ELN guidelines, cytoreductive therapy may be justified for low-risk patients with enlarging spleen, progressive leukocytosis or thrombocytosis, uncontrolled symptoms, or intolerance to or high need of phlebotomy. HU IFN-α Anagrelide Busulfan Pipobroman Radiophosphorus Cytoreductive agents alone or in combination HU=hydroxyurea; IFN-α=interferon-alpha. Barbui T, et al. J Clin Oncol. 2011;29(6):

5 Identifying inadequately controlled PV or ET Any of the following suggest inadequately controlled PV or ET 1,2 * Elevated haematocrit level 1,2 Elevated platelet count 1,2 Phlebotomy requirement while on HU 1,2 Burdensome symptoms 1 Elevated leukocyte count 1,2 Intolerance to initial cytoreductive therapy (eg, HU, IFN) 1,2 Getting a blood clot or bleeding 1,2 Change in the disease to myelofibrosis or leukaemia HU=hydroxyurea; PV=polycythaemia vera. *The definition of inadequately controlled PV is based on the definition of HU resistance or HU intolerance by the ELN criteria. 1. Reiter A, Harrison C. [Published online ahead of print February 19, 2016.] Curr Hematol Malig Rep. doi: /s Barbui T, et al. J Clin Oncol. 2011;29(6):

6 SHOULD INCLUDE: MONITORING FOR MPN PATIENTS The disease Is it well controlled? Is it progressing Is treatment still appropriate? The patient Understanding of disease Symptoms/Quality of life Any side effects Other change in health / vascular risk Building a therapeutic relationship 6

7 Clinical presentation at diagnosis of PV Clinical findings/history No history of thromboembolic events Blood count Hb: 19.2 g/dl HCT: 46.9% WBCs: /L PLTs: /L Bone marrow histology Trilineage hyperplasia Increased number of mature megakaryocytes of varying size Symptoms Blurred vision Severe headache Sex: Male Age: 59 Mutation analysis JAK2V617F positive Hb=haemoglobin; HCT=haematocrit; PLTs=platelets; WBCs=white blood cells. This patient case is hypothetical and may have been based in part on a real patient case. It is intended for educational purposes only. Not all patients will present or respond to therapy in the same manner. 7

8 Treatment history timeline Phlebotomy + low-dose aspirin HU 500 mg 5 /week HU 500 mg TIW + Phlebotomy ~6 /year? 15 years 2 years 2 years Clinical Assessment HCT: 52.2% WBCs: /L PLTs: /L Hb: 19.0 g/dl Splenomegaly (5 cm) Clinical Assessment PLTs: /L HU dose decreased Clinical Assessment HCT: 46.5% WBCs: /L PLTs: /L Hb: 17.9 g/dl Hb=haemoglobin; HCT=haematocrit; HU=hydroxyurea; PLTs=platelets; TIW=three times per week; WBCs=white blood cells. 8

9 Multiple phlebotomies required to maintain HCT while on HU Is This Patient s Disease Adequately Controlled? * ELN=European LeukemiaNet; HCT=haematocrit; HU=hydroxyurea. *The definition of inadequately controlled PV is based on the definition of HU resistance or HU intolerance by the ELN criteria. 9

10 Clinical presentation at diagnosis of ET Clinical findings/history Stable angina Blood count Hb: 13.1 g/dl HCT: 49.8% WBCs: /L PLTs: /L Bone marrow histology Megakaryocyte hyperplasia Symptoms None present Sex: Male Age: 51 Mutation analysis JAK2V617F positive Hb=haemoglobin; HCT=haematocrit; PLTs=platelets; WBCs=white blood cells. This patient case is hypothetical and may have been based in part on a real patient case. It is intended for educational purposes only. Not all patients will present or respond to therapy in the same manner. 10

11 Treatment history timeline IFN-α 3 MU/day HU 2 g QD? 10 years 2 years Clinical Assessment Clinical Assessment WBCs: /L PLTs: /L WBCs: /L PLTs: /L HCT: 46.5% FEELS DEPRESSED Splenomegaly: (8 cm) HCT: 44.2% HCT=haematocrit; IFN-α=interferon-alpha; MU=million units; PLTs=platelets; QD=once every day; WBCs=white blood cells. *The definition of inadequately controlled PV is based on the definition of HU resistance or HU intolerance by the ELN criteria. 11

12 Myelofibrosis: therapeutic landscape in 2016 Primary, post-et or post-pv myelofibrosis Calculate DIPSS MF score & assess MF symptoms (MPN-SAF) Low risk Asymptomatic Low risk Symptomatic Int-1 Symptomatic Int-2 & High risk Observation vs.? interferon??? JAK inhib? JAK inhib vs. allo SCT** vs. anemia Rx JAK inhibitor failure? Switch to another agent or switch to combination Reconsider Allo SCT JAK inhib Or clinical trial Allo SCT?? Clinical trial first if high-risk allo

13 Anemia Myelofibrosis: Clinical needs -orientated current therapy Clinical need Symptomatic splenomegaly Extramedulary hematopoiesis Drugs/Intervention Corticosteroids Danazol ESA Hydroxyurea Cladibrine, others Radiation therapy? Ruxolitinib Thalidomide Pomalidomide Lenalidomide Splenectomy Ruxolitinib Risk of thrombosis or recurrence Low-dose ASA Hydroxyurea Constitutional symptoms/qol None specifically directed Ruxolitinib Risk of leukemic transformation None specifically directed Improved survival Allo SCT (?) Ruxolitinib Barbui T, et al. J Clin Oncol 2011;29:

14 Clinical findings/history Clinical presentation at diagnosis Referred with large spleen History of pneumonia and psoriasis Blood count Hb: 10.3 g/dl HCT: 41.4% PLTs: /L EPO: 0.6 mu/ml Bone marrow histology Compatible with MF Symptoms Pruritus Fatigue Feeling abnormal Mutation analysis JAK2V617F positive Sex: Male Age: 66 EPO=erythropoietin; Hb=haemoglobin; HCT=haematocrit; MCV=mean corpuscular volume; PLTs=platelets. This patient case is hypothetical and may have been based in part on a real patient case. It is intended for educational purposes only. Not all patients will present or respond to therapy in the same manner. 14

15 Treatment history timeline pre 2010 HU 1 g QD? 1 year Splenomegaly (25 cm) Night sweats Clinical Assessment Fatigue and pruritus worsened Hb: 8.1 g/dl PLTs: /L Hb=haemoglobin; HCT=haematocrit; HU=hydroxyurea; PLTs=platelets; QD=once every day. *The definition of inadequately controlled PV is based on the definition of HU resistance or HU intolerance by the ELN criteria. 15

16 Treatment after 2010 Ruxolitinib a JAK inhibitor BEFORE AFTER Feels well 16

17 How to monitor MPN patients Who? Doctor expert, specialist, family ---- ALL Nurse & Where? At home Hospital Internet???

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