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Ruben A. Mesa, MD Professor of Medicine Chair, Division of Hematology & Medical Oncology

Overcoming your MPN!. Arizona, USA. Ruben A. Mesa, MD Professor of Medicine Chair, Division of Hematology & Medical Oncology Mayo Clinic Arizona, USA. Symptomatic Burden in MPNs. Why do symptoms matter in MPNs Development and testing of MPN Symptom Assessment

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Ruben A. Mesa, MD Professor of Medicine Chair, Division of Hematology & Medical Oncology

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  1. Overcoming your MPN! Arizona, USA Ruben A. Mesa, MD Professor of Medicine Chair, Division of Hematology & Medical Oncology Mayo Clinic Arizona, USA

  2. Symptomatic Burden in MPNs • Why do symptoms matter in MPNs • Development and testing of MPN Symptom Assessment • Current and Future Management of MPN Symptoms • Application in Clinical Trials and Next Steps

  3. Symptoms in 1179 MPD Patients Mesa et. al. Cancer 2007;109:68-76

  4. Burden of ET/PV MPN Associated Symptoms Macrovascular Risk Microvascular Symptoms

  5. Anemia • Symptoms • Fever • Weight Loss • Night Sweats • Itching • Bone pain • Fatigue Clonal MPN cells Enlarged Spleen Fibrosis In Marrow

  6. Burden of Myelofibrosis MF Associated Symptoms Splenomegaly Anemia/ Cytopenias

  7. Femme Ivre Se Fatigue 1902 O. Huber Collection Pablo Picasso (1881-1973)

  8. Symptomatic Burden in MPNs • Why do symptoms matter in MPNs • Development and testing of MPN Symptom Assessment • Current and Future Management of MPN Symptoms • Application in Clinical Trials and Next Steps

  9. Current Medications for MF • Medicines for • MF Anemia • Androgens • EPO • Thalidomide • Medicines for • MF Spleen • Hydroxyurea • Busulfan • 2-CDA • Splenectomy • Splenic Radiation • Medicines for • Anemia & • Spleen • Lenalidomide • Medicines for • MF Symptoms • None

  10. Rx Tox NET Effect Time on a Medical Therapy Net Symptom Burden Disease Sx Disease Sx

  11. ENDPOINTS Cure Prolong Life Absence Of Dz Delay Progression Compared to Controls? Relieve Burden of MPN Suffering Compared to ? Measured in the Eyes of the patient VALIDATION

  12. MPN-SAF (N=1433)Myeloproliferative Neoplasm Symptom Assessment Form Scherber et. al. 2011

  13. All for measurement of the Validated Brief Fatigue Inventory Scherber et. al. 2011

  14. Spleen/ Proliferation Related Vascular Psychiatric Cytokine Related QOL Scherber et. al. 2011

  15. MPN-SAF 10 Item Total Symptom Score (TSS) Scherber et. al. 2011

  16. MPN-SAF (N=1433)Myeloproliferative Neoplasm Symptom Assessment Form Mean TSS (0-10 Point Scale) P<0.001 Scherber et. al. 2011

  17. TSS MF Subtypes (N=284)Myeloproliferative Neoplasm Symptom Assessment Form Mean TSS (0-10 Point Scale) P = N.S. Between MF Subtypes Scherber et. al. 2011

  18. Prevalence of “Constitutional” Symptomsin 1433 MPN Patients * * * * * - P<0.001 Scherber et. al. 2011

  19. Severity of “Constitutional” Symptomsin 1433 MPN Patients * - P<0.001 * * * * Scherber et. al. 2011

  20. Spleen Derived Symptoms in 1433 MPN Patients Prevalence Severity * * * * * * - P<0.001 Scherber et. al. 2011

  21. Prevalence of “End Organ” Symptomsin 1433 MPN Patients * * * * * * - P<0.001 Scherber et. al. 2011

  22. Severity of “End Organ” Symptomsin 1433 MPN Patients * * - P<0.001 * * * Scherber et. al. 2011

  23. Decreased QOL in 1433 MPN Patients P<0.001 P<0.001 Scherber et. al. 2011

  24. EORTC ET Scales Comparison Ŧ Samuelsson et. al. (2006). "A Phase II Trial of Pegylated Interferon a-2b Therapy for Polycythemia Vera and Essential Thrombocythemia." Cancer. 106(11):2397-2405. *Scott et. al. (2008). "EORTC QLQ-C30 Reference Values." Publication from the EORTC Quality of Life Group. Found online at http://groups.eortc.be/qol/downloads/reference_values_manual2008.pdf.

  25. EORTC PV Scales Comparison Ŧ Samuelsson et. al. (2006). "A Phase II Trial of Pegylated Interferon a-2b Therapy for Polycythemia Vera and Essential Thrombocythemia." Cancer. 106(11):2397-2405. *Scott et. al. (2008). "EORTC QLQ-C30 Reference Values." Publication from the EORTC Quality of Life Group. Found online at http://groups.eortc.be/qol/downloads/reference_values_manual2008.pdf.

  26. EORTC MF Scales Comparison FOR INTERNAL USE ONLY.  NOT FOR DETAILING.  DO NOT COPY OR DISTRIBUTE.   Ŧ Samuelsson et. al. (2006). "A Phase II Trial of Pegylated Interferon a-2b Therapy for Polycythemia Vera and Essential Thrombocythemia." Cancer. 106(11):2397-2405. *Scott et. al. (2008). "EORTC QLQ-C30 Reference Values." Publication from the EORTC Quality of Life Group. Found online at http://groups.eortc.be/qol/downloads/reference_values_manual2008.pdf.

  27. Martyrdom of Saint Sebastian 1473 National Gallery, London Antonio del Pollaiuolo (1431-1498)

  28. Symptomatic Burden in MPNs • Why do symptoms matter in MPNs • Development and testing of MPN Symptom Assessment • Current and Future Management of MPN Symptoms • Application in Clinical Trials and Next Steps

  29. Managing MPN Fatigue • Exercise • Healthy Lifestyle and Diet • Correction of Iron Deficiency When Possible • Stimulants • Ritalin/Provigil/ Nuvigil • JAK2 Inhibitors

  30. Managing MPN Micro-vascular Sx • Aspirin • Smoking Cessation • Management of Blood Counts • ? Additional Anti-platelet therapy

  31. Managing MPN Itching (Pruritus) • Anti-histamines • Therapeutic UV Light • Physical Measures (avoiding hot baths, air drying) • Interferon / Peg Interferon • JAK2 Inhibitors

  32. Managing MPN Cachexia & Splenomegaly • JAK 2 inhibitors (Both) • Hydroxycarbamide (Spleen alone) • Splenectomy (Spleen Alone) • Splenic Radiation (Spleen Alone) • Other Chemotherapy (Spleen Alone)

  33. JAK2 Inhibitors in Development for MF Clinical Phase of Testing

  34. Ruxolitinib Therapy Associated with Rapid and Durable Improvement In Symptoms Associated with Enlarged Spleen Mesa et. al. Cancer 2011

  35. Ruxolitinib Therapy Associated with Rapid and Durable Reduction of Symptoms Associated with Elevated Inflammatory Cytokines Mesa et. al. Cancer 2011

  36. Ruxolitinib Phase II Mesa et. al. Cancer 2011

  37. S. Verstovsek, H. Kantarjian, R. Mesa, et. al. NEJM 2010;363:1117-27

  38. Short Term Thrombosis & Bleeding Long Term Post ET/PV MF & MPN Blast Phase High and ? Int Risk = Cytoreduction All Risk = ASA ET PV No Known Therapy ? JAK2 Inhibitors

  39. Management of PV • ALL PV Patients • Maintain HCT <45% Men, 42% Women • Low Dose ASA • Aggressive control of CV risk factors • Cytoreduction • High Risk or • Intol to Phlebotomy, Increasing Spleen, Severe Sx Plt >1500 x 10(9)/L, or prog WBC • Medications • Hydroxyurea or Interferon alpha as Front line (or second) • Busulfan, pipobroman, P-32 as second line Barbui et. al. LeukemiNET Consensus Guidelines JCO 2011 in press

  40. Management of ET • ALL ET Patients • Low Dose ASA • Aggressive control of CV risk factors • Cytoreduction • High Risk • Medications • Hydroxyurea as Front line • Anagrelide second line • Interferon alpha third line • Busulfan, pipobroman, P-32 for elderly Barbui et. al. LeukemiNET Consensus Guidelines JCO 2011 in press

  41. Morphologic change after IFN therapy in a patient with primary myelofibrosis (After Median 3 years of Rx). • Silver et. al. Blood 2011 • 17 “Early” PMF (MF<Grade 3) • IWG (11 low, 6 Int 1) • INFa2b or PEG Infa-2a • IWG-MRT • 2 CR, 7 PR, 1 CI (59% Response) • Gowin et. al. ASH 2011 • 17 “Early” PMF (MF<Grade 3) • PEG Infa-2a • IWG-MRT • 1 CR, 2 PR, 1 CI (29% Response) Silver R T et al. Blood 2011;117:6669-6672

  42. Verstovsek et. al. ASH 2010; Abstract 313

  43. Verstovsek et. al. ASH 2010; Abstract 313

  44. Verstovsek et. al. ASH 2010; Abstract 313

  45. Verstovsek et. al. ASH 2010; Abstract 313

  46. Verstovsek et. al. ASH 2010; Abstract 313

  47. The Broken Column 1944 Museo Dolores Olmedo, Mexico Frida Kahlo (1907-1954)

  48. Symptomatic Burden in MPNs • Why do symptoms matter in MPNs • Development and testing of MPN Symptom Assessment • Current and Future Management of MPN Symptoms • Application in Clinical Trials and Next Steps

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