Arizona, USA ©2011 MFMER | 3133089-1 Ruben A. Mesa, MD Professor & Chairman, Division of Hematology & Medical Oncology Deputy Director, Mayo Clinic Cancer.

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Presentation transcript:

Arizona, USA ©2011 MFMER | Ruben A. Mesa, MD Professor & Chairman, Division of Hematology & Medical Oncology Deputy Director, Mayo Clinic Cancer Center Mayo Clinic – Arizona, USA What should you expect of your MPN Therapy?

©2011 MFMER | What should you expect of your MPN Therapy? Individualizing Therapy What is the spectrum of disease burden and risk in MPNs? What are expectations of therapy? Current and evolving treatment options for MPN patients

Burden of ET/PV Microvascular Symptoms Microvascular Symptoms Macrovascular Risk MPN Associate d Symptom s Burden of Myelofibrosis Anemia/ Cytopenis Anemia/ Cytopenis Splenomegaly MF Associated Symptoms Et & PV Associated Symptoms

Evolution of MPN Symptom Assessment Tools MF–SAF 2009 (19 items) MF-SAF 2.0 (7 items 2011) JCO in Press MF–SAF 2009 (19 items) MF-SAF 2.0 (7 items 2011) JCO in Press Brief Fatigue Inventory (BFI) – 9 Items Brief Fatigue Inventory (BFI) – 9 Items Spleen Sx 4 Items Spleen Sx 4 Items Constitutional Sx 5 Items Constitutional Sx 5 Items QOL 1 Item Vascular and Ψ Sx 9 Items Vascular and Ψ Sx 9 Items MPN–SAF 2011 (27 items) Blood 2011 MPN-SAF TSS (10 items 2012) JCO 2012 MPN–SAF 2011 (27 items) Blood 2011 MPN-SAF TSS (10 items 2012) JCO 2012 MPN-SAF Languages English French German Spanish Dutch Swedish Italian Portuguese Mandarin Japanese Hebrew MPN-SAF Languages English French German Spanish Dutch Swedish Italian Portuguese Mandarin Japanese Hebrew

Quartile 1 (Q1): 0-24% Quartile 2 (Q2): 25-49% Quartile 3 (Q3): 50-74% Quartile 4 (Q4): % Percentile MPN-SAF TSS Q1 TSS <8 Q2 TSS Q3 TSS Q4 TSS >32 ParameterP value of Comparison Age0.24 Gender F>M<0.001 MPN Diagnosis<0.001 Subtype of MF0.86 IPSET (ET Risk)0.18 PV Risk (PV)0.30 DIPSS (MF Risk)<0.001 MPN Symptom Burden by Quartiles 1858 MPN-SAF Respondents

ET (N=775) PV (N=654) MF (N=423) Q1 – 30%Q2 – 26% Q3 – 24%Q4 – 20% Q1 – 17%Q2 – 21% Q3 – 26% Q4 – 36% Q1 – 25%Q2 – 23% Q3 – 26%Q4 – 26%

MPN Symptom Burden by Quartiles Comparison between MPN Diagnosis and Quartiles P<0.001

EORTC QLQ-C30 Scores in MF and Other Hematologic Malignancies and Solid Tumors EORTC QLQ-C30 Myelofibrosis COMFORT-I placebo arm (N=147*) Myelofibrosis (N=96) 1 CML (N=73) 2 Myeloma (N=944) 3 Breast (N=2782) 3 Lung (N=3332) 3 Recurrent/ metastatic cancers (N=4812) 3 Global Health Status/QoL Functional Subscales Physical Functioning Role Functioning Emotional Functioning Cognitive Functioning Social Functioning Symptom Scales/Single Items Fatigue Pain Dyspnea Insomnia Appetite loss = Worsening Direction

What is quality of life Quality of Life Increasing ?

Definitions HRQOL in MPNs? Σ MPN related symptoms Medication related toxicities Problems from prior MPN complications Stressors from having their MPN Financial Emotional Intrapersonal Co-morbidities Hassle of medical care

©2011 MFMER | What should you expect of your MPN Therapy? Individualizing Therapy What is the spectrum of disease burden and risk in MPNs? What are expectations of therapy? Current and evolving treatment options for MPN patients

IPSET (ET – 3 groups) Survival Thrombosis Risk PV Risk (4 groups) Survival Leukemia Rates DIPSS (PMF – 4 groups) Survival Age≥ 60 (2pts) vs. < 60≥70 (3pts) (2pts), <60 ≥65 (1pt) vs. <65 Leukocytes≥ 11 (1pt) vs. < 11 x 10 9 /L ≥15 (1 point) vs. <15 x 10 9 /L >25 (1pt) vs. ≤25 x 10 9 /L Hemoglobin<10 (2 pts) vs. ≥10g/dL Constitutional Symptoms Present # (1pt) vs. Absent Blasts≥1% (1pt) vs. <1% Prior Thrombosis Yes (1 point) vs. No Risk Group Point Cutoffs 0; 1-2; 3-4 pts.0; 1-2; 3; 4 pts.0; 1-2; 3-4; ≥4 pts. Evolving MPN Prognostic Scales Tefferi ASH 2011 Passamonti Blood 2012 Passamonti Blood 2010 # = >10% Weight Loss over prior 6 months, Night Sweats, Unexplained Fever

New Response Criteria for MPNs ET 2 PV 2 MF 1 Complete response  Partial response  Clinical improvement  Stable disease  No response  Relapse  Other responsesMolecular Cytogenetic and molecular 1. Tefferi A et al. Blood. 2013;122: Barosi G et al. Blood. 2013;121:

New Response Criteria for MF: Complete Response 1 EMH: extramedullary hematopoiesis 1. Tefferi A et al. Blood. 2013;122: Bone marrow: Age-adjusted normocellularity; <5% blasts; ≤Grade 1 MF; and Peripheral blood: Hemoglobin ≥ 100 g/L and <UNL; Neutrophils ≥ 1 x 10 9 /L and <UNL; Platelets ≥ 100 x 10 9 /L and <UNL; <2% immature myeloid cells; and Clinical: Resolution of disease symptoms Spleen and liver not palpable No evidence of EMH Required criteria: for all response categories, benefit must last for ≥12 wks to qualify as a response

New Response Criteria for MF: Partial Response 1 1. Tefferi A et al. Blood. 2013;122: Peripheral blood: Hemoglobin ≥ 100 g/L and <UNL; Neutrophils ≥ 1 x 10 9 /L and <UNL; Platelets ≥ 100 x 10 9 /L and <UNL; <2% immature myeloid cells and Clinical: Resolution of disease symptoms; spleen and liver not palpable; no evidence of EMH Bone marrow: Age-adjusted normocellularity; <5% blasts; ≤grade 1 MF, and Peripheral blood: Hemoglobin ≥ 85 but <100 g/L and <UNL; Neutrophils ≥1 x 10 9 /L and <UNL; Platelets ≥50, but <100 x 10 9 /L and <UNL; <2% immature myeloid cells and Clinical: Resolution of disease symptoms; spleen and liver not palpable; no evidence of EMH or

New Response Criteria for MF: Other Categories 1 1. Tefferi A et al. Blood. 2013;122: Clinical improvement Achievement of anemia, spleen, or symptoms response without progressive disease or increase in severity of anemia, thrombocytopenia, or neutropenia Anemia response Transfusion-independent pts: a ≥20 g/L increase in Hb level Transfusion-dependent pts: becoming transfusion independent Spleen response Baseline splenomegaly that is palpable at 5-10 cm, below the LCM, becomes not palpable, OR Baseline splenomegaly that is palpable at >10 cm, below the LCM, decreases by ≥50% Baseline splenomegaly that is palpable at <5 cm, below the LCM, is not eligible for spleen response Symptoms response A ≥50% reduction in the MPN-SAF TSS CI: clinical improvement; LCM: left costal margin.

Revised MPN Response Criteria New response criteria remain clinically derived and focus on resolution of marrow histologic changes, blood counts, spleen size, symptom improvement, and lack of vascular events or progression All require over 12 weeks of benefit to be counted as response Value and measurement of stability (clinically or histologically) still not captured Validation of value of response levels needed ©2011 MFMER |

©2011 MFMER | What should you expect of your MPN Therapy? Individualizing Therapy What is the spectrum of disease burden and risk in MPNs? What are expectations of therapy? Current and evolving treatment options for MPN patients

Management of PV/ET 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 T, et. al. LeukemiNET Consensus Guidelines. JCO 2011;29:

Kiladjian JJ, et al. Blood 2008;112:3065

Morphologic change after IFN therapy in a patient with primary myelofibrosis (After Median 3 years of Rx). Silver R T et al. Blood 2011;117: Silver et. al. Blood “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 “Early” PMF (MF<Grade 3) PEG Infa-2a IWG-MRT 1 CR, 2 PR, 1 CI (29% Response)

2014 Therapeutic options for MF Anemia Androgens rEPO IMiDs Myeloproliferation And Splenomegaly Ruxolitinib Hydroxyurea Busulfan Cladribine Splenectomy Radiation Allogeneic Stem cell Transplantation (ASCT) Cure Ruxolitinib Constitutional Symptoms Low riskInt-1 riskInt-2 riskHigh risk JAK2 inhibitor JAK1 inhibitor Telomerase Inhibitor Histone Deacetylase inhibitors IFN-α Combination therapy ASCT Experimental therapy Observation

JAK Inhibitors and Status of Development Myelofibrosis as lead indications ©2011 MFMER | No Longer in Development For MPNs * Now Testing in PV * * * *

Mean Daily Dose of Ruxolitinib Over Time 24 Approximately 70% of patients had dose adjustments during the first 12 weeks of therapy By week 24, patients originally randomized to RUX 15 mg BID and 20 mg BID were titrated to a mean dose of ~10 mg BID and mg BID, respectively Mean Daily Dose (mg, BID) ± SEM Weeks 20 mg BID starting dose 15 mg BID starting dose mg BID mg BID Number of patients ASH 2013

Percentage Change in Spleen Size 25 Mean reductions in spleen volume and palpable spleen length with ruxolitinib were stable over time RuxolitinibPlacebo Weeks Mean Percentage Change from Baseline n = Weeks RuxolitinibPlacebo n = Mean Percentage Change from Baseline Spleen VolumeSpleen Length ASH 2013

Durability of Spleen Volume Reduction 26 ≥35% reduction: Time from first 35% reduction to <35% reduction and 25% increase from nadir. ≥10% reduction: Time from first 35% reduction to <10% reduction from baseline. In patients originally randomized to ruxolitinib, 59% achieved a ≥35% reduction in spleen volume

Improvements in EORTC QLQ-C30 Over Time Arrows indicate improvement RUXPBO Global Health Status/QoL Mean Change From Baseline Weeks Fatigue Mean Change From Baseline Weeks Physical Functioning Mean Change From Baseline Weeks Role Functioning Mean Change From Baseline Weeks

JAK1 & 2 Inhibitors in MPNs – Efficacy Summary – As of ASH 2013 MyelofibrosisPolycythemia Vera Essential Thrombocythemia SpleenConst. Sympt. AnemiaSurvival  Counts Const. Sympt.  Vasc Events  Counts Const. Sympt.  Vasc Events Ruxolitinib - ApprovedP III P II SAR – PH III JAKARTA (HOLD) P III P IIP III Pacritinib- PIII Ongoing (Persist MF) P II CYT387P II LY P I NS-018 BMS PH II INCB039110P I CEP701P II ©2011 MFMER | Not Reported Yet Not Reported Yet Yes No Occasional Ongoing Trials

JAK1 & 2 Inhibitors in MPN – Toxicity ASH 2013 Hematological Toxicities Gastrointestinal/ Renal Toxicities Neurological Toxicities Anemia  ANC  PLT NauseaDiarr- hea  LFTs Or CR  Lipase Head- ache DizzyNeuroP/ Parathia Ruxolitinib - Approved 23%7%11%2%0.6% SAR – PIII Ongoing (MF) 41%6%11%0%5%1%W. E. % ? Pacritinib- PIII Ongoing (MF) 6%0%18%6% CYT387 PII Ongoing (MF) 10%2%20%1% INCB (JAK1) – PI/II MF 28%27%10% BMS %10% 0% LY %0%3%8% Renal ©2011 MFMER | <10% % % % % % % % % % Toxicity Color – Represents All Grades ( Grade ¾ Toxicity - Percentage in Table Above)

MPNs – Plateau vs. Decline ©2011 MFMER | ET – Possible Plateau Asymptomatic Thrombocytosis No Vascular Events ET – Possible Plateau 2 Symptomatic Thrombocytosis Sinus Venous Thrombosis Time Clinical Status PV – Possible Plateau 2 Symptomatic Erythrocytosis No Vascular Events Post PV MF 6 Months worsening Fatigue 10 kg weight loss Massive spleen MF on Successful JAK2 Rx Improving Weight Decreased Spleen Improved Survival

MPNs – Cumulative Benefits ©2011 MFMER | Time Clinical Status Improved Symptom Burden Improved Spleen Burden Improved Survival Ruxolitinib

MPNs – Cumulative Benefits Single Agent Trials JAK2 Inhibitors Compared to Ruxo ©2011 MFMER | Time Clinical Status Improved Symptom Burden Improved Spleen Burden Improved Survival ? Other Benefit -Less cytopenias -Improved activity ? Other Benefit -Less cytopenias -Improved activity STUDY (JAK2/FLT3 Inhibitor) NS-018 (PH I/II) NCT STUDY (JAK2/FLT3 Inhibitor) NS-018 (PH I/II) NCT STUDY (JAK2/FLT3 Inhibitor) Pacritinib (SB1518) (PH III vs. BAT) NCT STUDY (JAK2/FLT3 Inhibitor) Pacritinib (SB1518) (PH III vs. BAT) NCT STUDY (JAK2 Inhibitor – Also ET and PV) LY (PH I/II) NCT STUDY (JAK2 Inhibitor – Also ET and PV) LY (PH I/II) NCT STUDY (JAK2/JAK1 Inhibitor) Momelotinib (CYT387) (PH III vs. Ruxo) NCT STUDY (JAK2/JAK1 Inhibitor) Momelotinib (CYT387) (PH III vs. Ruxo) NCT

IMiDs in MF: Summary of Clinical Data HBPLTSPLNREF THAL 29%38%41%Barosi 2002 THAL-PRED 62%75%19%Mesa 2002 LEN 22%50%33%Tefferi 2006 LEN-PRED 19%?9%Mesa 2010 LEN-PRED 30%?42%Quintas-Cardama 2009 POM (0.5mg/day) >50%?<25%Mesa 2010 POM+/-PRED 30-40%40%<10%Tefferi 2008

MPNs – Cumulative Benefits Ruxolitinib + drug X for Anemia ©2011 MFMER | Time Clinical Status Improved Symptom Burden Improved Spleen Burden Improved Survival Improved Anemia Burden STUDY COMBINATION (JAK2 PLUS Androgen) Ruxolitinib Plus Danazol Mayo Clinic (AZ) and Mt. Sinai Trial: NCT STUDY COMBINATION (JAK2 PLUS Androgen) Ruxolitinib Plus Danazol Mayo Clinic (AZ) and Mt. Sinai Trial: NCT STUDY COMBINATION(JAK2 PLUS Hypomethylation) Ruxolitinib Plus Azacitidine MDACC Trial: NCT STUDY COMBINATION(JAK2 PLUS Hypomethylation) Ruxolitinib Plus Azacitidine MDACC Trial: NCT STUDY COMBINATION (JAK2 PLUS IMID) Ruxolitinib Plus Lenalidomide NCT STUDY COMBINATION (JAK2 PLUS IMID) Ruxolitinib Plus Lenalidomide NCT STUDY COMBINATION (JAK2 PLUS IMID) Ruxolitinib Plus Pomalidomide Germany (ULM): NCT STUDY COMBINATION (JAK2 PLUS IMID) Ruxolitinib Plus Pomalidomide Germany (ULM): NCT

MPNs – Cumulative Benefits Ruxolitinib + drug X for Deeper Marrow Changes Impact Clinical Status Improved Symptom Burden Improved Spleen Burden Improved Survival Improved Marrow Dysfunction STUDY COMBINATION (JAK2 PLUS HDAC Inhibitors) Ruxolitinib Plus Panobinostat Mt. Sinai Trial: NCT UK Trial: NCT STUDY COMBINATION (JAK2 PLUS HDAC Inhibitors) Ruxolitinib Plus Panobinostat Mt. Sinai Trial: NCT UK Trial: NCT STUDY COMBINATION (JAK2 PLUS LOXL2 Inhibitors) Ruxolitinib Plus GS-6624 NCT STUDY COMBINATION (JAK2 PLUS LOXL2 Inhibitors) Ruxolitinib Plus GS-6624 NCT STUDY COMBINATION (JAK2 PLUS rhPTX-2 (Anti-fibrosing)) Ruxolitinib Plus PRM -151 Opening Soon STUDY COMBINATION (JAK2 PLUS rhPTX-2 (Anti-fibrosing)) Ruxolitinib Plus PRM -151 Opening Soon STUDY COMBINATION (JAK2 PLUS PI3 Kinase Inhibitor) Ruxolitinib Plus BKM120 NCT STUDY COMBINATION (JAK2 PLUS PI3 Kinase Inhibitor) Ruxolitinib Plus BKM120 NCT STUDY COMBINATION (JAK2 PLUS Hedgehog Inhibitor) Ruxolitinib Plus LDE225 NCT STUDY COMBINATION (JAK2 PLUS Hedgehog Inhibitor) Ruxolitinib Plus LDE225 NCT

MPNs – Cumulative Benefits Single Agent Trials Alternate Targets Time Clinical Status Improved Symptom Burden Improved Spleen Burden Improved Survival ? Other Benefit -Less cytopenias -Improved activity ? Other Benefit -Less cytopenias -Improved activity STUDY (Interferons) Peg Interferon α2b in “Early” MF Cornell Lead: NCT STUDY (Interferons) Peg Interferon α2b in “Early” MF Cornell Lead: NCT STUDY (Activin - ActRIIA-IgG1Fc) Sotatercept (ACE 011) MDACC: NCT STUDY (Activin - ActRIIA-IgG1Fc) Sotatercept (ACE 011) MDACC: NCT STUDY (Telomerase Inhibitor) Imetelstat (GRN163L) Mayo Clinic (Rochester): NCT STUDY (Telomerase Inhibitor) Imetelstat (GRN163L) Mayo Clinic (Rochester): NCT STUDY (JAK1 Inhibitor) INCB (PH II) NCT STUDY (JAK1 Inhibitor) INCB (PH II) NCT

MPNs – Cumulative Benefits Difficult PV-ET Clinical Status Improved Symptom Burden Improved Spleen Burden Improved Survival Improved Marrow Dysfunction STUDY COMBINATION (PV) Ruxolitinib Vs. Hydroxyurea (RELIEF) NCT STUDY COMBINATION (PV) Ruxolitinib Vs. Hydroxyurea (RELIEF) NCT STUDY (ET and PV) MPD-RC 112 Peg Inf a2a vs. Hydroxyurea (PH III) NCT STUDY (ET and PV) MPD-RC 112 Peg Inf a2a vs. Hydroxyurea (PH III) NCT STUDY (ET and PV) MPD-RC 111 Peg Inf a2a AFTER Hydroxyurea (PH III) NCT STUDY (ET and PV) MPD-RC 111 Peg Inf a2a AFTER Hydroxyurea (PH III) NCT STUDY (PV) AOP Peg Inf a2a vs Hydroxyurea (PH III) NCT STUDY (PV) AOP Peg Inf a2a vs Hydroxyurea (PH III) NCT FUTURE STUDY COMBINATION JAK2 Inhibitor Plus PEG INF  2a/b FUTURE STUDY COMBINATION JAK2 Inhibitor Plus PEG INF  2a/b Improved Vascular Event Risk (?PV)

Myeloproliferative Disorders Research Consortium Trial Polycythemia Vera and Essential Thrombocythemia MPD-RC 112 (NCT – clinicaltrials.gov) Randomized Trial of Pegylated Interferon Alfa-2a versus Hydroxyurea Therapy in the Treatment of High Risk Polycythemia Vera (PV) and High Risk Essential Thrombocythemia (ET) Registered & Randomized High Risk ET and PV (< 3 Months Prior Hydroxyurea) Registered & Randomized High Risk ET and PV (< 3 Months Prior Hydroxyurea) PEG INF Alfa-2a Target dose 90 mcg/week Weekly Dosing ≥2 years of therapy in responders PEG INF Alfa-2a Target dose 90 mcg/week Weekly Dosing ≥2 years of therapy in responders HYDROXYUREA Titrated Dosing to Response Daily Dosing MPD-RC 111 in HYDROXYUREA Failures HYDROXYUREA Titrated Dosing to Response Daily Dosing MPD-RC 111 in HYDROXYUREA Failures ENDPOINTS Primary: Complete response by ELN Criteria Secondary: Partial response rate by ELN criteria, JAK2-V617F Allele Burden, Vascular Events, MPN Symptoms, Tolerability, Progression ENDPOINTS Primary: Complete response by ELN Criteria Secondary: Partial response rate by ELN criteria, JAK2-V617F Allele Burden, Vascular Events, MPN Symptoms, Tolerability, Progression Key Eligibility Criteria High risk PV or ET within 3 years from diagnosis No prior cytoreductive treatment (interferon or pegasys) other than hydroxyurea for up to 3 months (prior phlebotomy, aspirin, and/or anagrelide allowed) Age of 18 or older with relatively normal kidney and liver function No other serious medical problems Key Eligibility Criteria High risk PV or ET within 3 years from diagnosis No prior cytoreductive treatment (interferon or pegasys) other than hydroxyurea for up to 3 months (prior phlebotomy, aspirin, and/or anagrelide allowed) Age of 18 or older with relatively normal kidney and liver function No other serious medical problems Questions contact MPD-RC ( John Mascarenhas, MD Phone: 1 (212)

Verstovsek S, et. al. Blood (ASH) 2010;116: Abstract 313

Time to First Phlebotomy (n=1) or Discontinuation (n=8) 40 74% (25/34) remained on study and phlebotomy-free for at least 144 weeks NOTE: Analysis does not include phlebotomies that occurred in the first 4 weeks of treatment. Verstovsek S et. al. Blood (ASH) 2012;120:abstr 804

Reduction in PV-Associated Symptoms Clinically meaningful improvements in pruritus, night sweats, and bone pain observed within 4 weeks of initiating therapy and sustained through Week ITT analysis: Patients who discontinued are counted as not having response for all study visits that they would have completed up to the date of analysis. Verstovsek S et. al. Blood (ASH) 2012;120:abstr 804

Medicine Wheel of Health “Integrative Medicine”

MPN-QOL International Study Group MEASURE Trial Serial assessment of MPN symptoms and QOL in all currently available therapies SYMPTOM Trial Serial assessment of the BMT experience in MPN symptoms (and BMT/GVHD symptoms) and QOL Current Landmark Survey mpnsurvey.com ©2011 MFMER | Supported by a grant from the MPN Foundation

Patient Goals & Input Improving Symptom Burden /HR QOL “Balancing” Spleen/ Cytoses/ Cytopenias Extending Life CURE ©2011 MFMER | Individualizing MPN Pharmacotherapy

©2011 MFMER | Acknowledgements Argentina Ana Clara Kneese, MD Federico Sackmann, MD Australia David M Ross MBBS, PhD Cecily Forsyth John Seymour, MBBS, PhD Karen Hall, MD Kate Burbury MD Tam Constantine, MD Canada Lynda Foltz, MD Vikas Gupta, MD China Hsin-An Hou, MD Huan-Chau Lin, MD Hung Chang, MD Ming-Shen Dai, MD Yuan-Bin Yu, MD Yung-Chen Su, MD Zhijian Xiao, MD Denmark Christen Lykkegaard Andersen, MD Hans Hasselbalch, MD France Brigitte Dupriez, MD Jean-Jacques Kiladjian, MD Jean-Loup Demory MD Magali Demilly, PhD Germany Heike L. Pahl, PhD Ireland Mary Francis McMullen, MD Israel Martin Ellis, MD Italy Alessandro M. Vannucchi, MD Francesco Passamonti, MD Giovanni Barosi, MD Tiziano Barbui, MD Netherlands Harry Schouten, MD, PhD Jan Jacques Michiels, MD Karin Klauke, MD Peter te Boekhorst, MD Sonja Zweegman, MD PhD Stephanie Slot, MD Suzan Commandeur, MD New Zealand Hilary Blacklock, MD Panama Francis Guerra, MD Singapore Wee Joo Chng, MB ChB Spain Ana Kerguelen Fuentes, MD Carlos Besses, MD Francisco Cervantes, MD Dolores Fernandez-Casados Sweden Andreasson Bjorn, MD Elisabeth Ejerblad, MD Gunnar Birgegard, MD Jan Samuelsson, MD Johanna Ablesson, MD Peter Johansson, MD UK Anthony Green, MD Claire N. Harrison, MD Deepti Radia, MD Uruguay Pablo Muxi, MD USA Alison Moliterno, MD Brady Stein, MD MHS Casey O'Connell Catriona Jamieson Daniel Rubin, ND Elizabth Hexner Hala Simm Jason Gotlib, MD Jeff Sloan, PhD Jessica Altman, MD Joseph Prchal, MD Kimberly Hickman Martin Tallman, MD Mike Boxer, MD Olatoyosi Odenike, MD Robert Silver, MD Ross Levine, MD Soo Jin Kim Srdan Verstovsek, MD