Imatinib & Ponatinib. Two ends of the spectrum in 2016s reality
|
|
- Julie Stevenson
- 6 years ago
- Views:
Transcription
1 Imatinib & Ponatinib Two ends of the spectrum in 2016s reality
2 CML 2016 Benefits & risks Steve O Brien CML Horizons, May 2016
3 Disclosures Research funding, participation in company trial, speaker, consultant, meeting assistance (last 3 years): Ariad, BMS, Novartis, Pfizer, Gilead, Sanofi Aventis Member: NCRI Clinical Studies Group NCRI CML Working Group NICE Technology Appraisal Committee C NHS Cancer Drug Fund Panel Co-Chair Employer: Newcastle University Stock: none
4 Benefits
5 Risks
6 Where next?
7 Imatinib Development License TKIs in CML NICE approved (UK) Off patent 2016 Dasatinib Nilotinib Bosutinib (radotinib) Ponatinib Cancer Drug Fund CDF: Cancer drug fund; CML: Chronic myeloid leukaemia; NICE: National Institute for Health and Care Excellence The following websites were last accessed in April 2015: 1) NICE Imatinib: 2) EMA Sprycel: 3) NICE nilotinib: 4) NICE bosutinib: 5) NICE ponatinib:
8 Benefits
9 Imatinib 1999 Safe Effective Cost effective
10 814 patients in total Recruitment closed Feb hospitals set up,145 recruited patients
11 SPIRIT 2: PCR data at 24 months Imatinib n=406 On treatment 246/406 (60.6%) Off treatment 160/406 (39.4%) Achieved MR3 Response 187/406 (46.0%) Achieved MR4.5 Response 58/406 (14.3%) Total Cohort n=812 Dasatinib n=406 Off treatment 116/406 (28.6%) On treatment 290/406 (71.4%) Δ = 11.5% p<0.001 Achieved MR3 Response 234/406 (57.5%) Δ = 5.9% P=0.026 Achieved MR4.5 Response 82/406 (20.2%) April 2015
12 DASISION: OS & PFS Dasatinib 100 mg OD (n=259) Imatinib 400 mg OD (n=260) Hazard ratio (95% CI) Total number of deaths, n Estimated 5-year OS, % (95% CI) 91 (87 94) 90 (85 93) 1.01 ( ) Estimated 5-year PFS, % (95% CI) 85 (80 89) 86 (80 89) 1.06 ( ) Causes of death were cardiovascular disease (2 dasatinib, 1 imatinib); disease progression (9 dasatinib, 17 imatinib); infection (11 dasatinib, 1 imatinib); other malignancy, septic shock and cardiac failure, multi-organ failure, and whole body swelling (1 each dasatinib); stem cell transplantation complications and unknown (2 each imatinib); severe chest pain, clinical deterioration and decrease in performance status, and fatal bleeding (1 each imatinib) On-study treatment and in follow-up after discontinuation of randomized treatment. CI, confidence interval; OS, overall survival; PFS, progression-free survival. Cortes J, et al. Presented at: 2014 Annual Meeting of ASH; San Francisco, CA. Oral presentation.
13 ENESTnd: OS and CML-Related Deaths Nilotinib 300 mg BID (n = 282) Nilotinib 400 mg BID (n = 281) Imatinib 400 mg OD (n = 283) Total deaths, n a KM-estimated 5-year OS, % Hazard ratio vs imatinib (95% CI) 0.80 ( ) 0.44 ( ) P value vs imatinib Deaths in patients with advanced CML, n b KM-estimated 5-year freedom from death due to advanced CML, % Hazard ratio vs imatinib (95% CI) 0.37 ( ) 0.24 ( ) P value vs imatinib a OS events included death from any cause at any time (on core or extension treatment or during follow-up after treatment discontinuation). b Patients for whom the principal cause of death was either study indication or unknown or not reported but occurred subsequent to a documented progression to AP/BC. Hughes T, et al. Oral presentation at the Annual Meeting of EHA 2014, Abstract S677. Data cutoff: September 30,
14 Ponatinib: A Pan-BCR-ABL Inhibitor Rationally designed inhibitor of BCR- ABL Active against T315I mutant Unique approach to accommodating gatekeeper isolucine residue Potent activity against an array of BCR-ABL variants Once-daily oral activity Half-life 22 hours Also targets other therapeutically relevant kinases: Inhibits FLT3, FGFR, VEGFR and PDGFR, and c-kit T315I gatekeeper residue O Hare T, et al. Cancer Cell. 2009;16:
15 Ponatinib: PACE study
16 Duration of Response to Ponatinib in CP-CML 83% of responders estimated to remain in MCyR at 36 months a Failed to meet criteria for MCyR in 2 consecutive assessments 28 days apart, or discontinued after a single assessment in which the criteria for MCyR were not met b Kaplan-Meier estimate
17 Risks
18
19 Treatment-Emergent AE n (%) CP-CML (N=270) SAE n (%) AE n (%) PACE (ponatinib 45mg) Vascular Occlusive Events AP-CML (N=85) SAE n (%) AE n (%) BP-CML (N=62) SAE n (%) AE n (%) Ph+ ALL (N=32) SAE n (%) AE n (%) Total (N=449) Arterial thrombotic 61 (23) 44 (16) 17 (20) 12 (14) 6 (10) 3 (5) 2 (6) 2 (6) 86 (19) 61 (14) Cardiovascular 27 (10) 20 (7) 12 (14) 7 (8) 3 (5) 2 (3) 1 (3) 0 (0) 43 (10) 29 (7) Cerebrovascular 27 (10) 18 (7) 5 (6) 4 (5) 0 (0) 0 (0) 1 (3) 1 (3) 33 (7) 23 (5) Peripheral vascular 23 (9) 14 (5) 3 (4) 2 (2) 3 (5) 1 (2) 2 (6) 2 (6) 31 (7) 19 (4) Venous thromboembolic 11 (4) 7 (3) 3 (4) 1 (1) 6 (10) 5 (8) 3 (9) 1 (3) 23 (5) 14 (3) Total vascular occlusive events 67 (25) 49 (18) 19 (22) 13 (15) 10 (16) 7 (11) 5 (16) 3 (9) 101 (23) 72 (16) Exposure-Adjusted Incidence (Number of Patients With Events per 100 Patient-Years) by Disease Group Cumulative exposure, patient-years Exposure-adjusted incidence of vascular occlusive events SAE n (%) Median time to onset of arterial thrombotic events in CP-CML: 281 (8-952) days Median time to onset of venous thromboembolic events in CP-CML: 604 (62-802) days Overall, 5 pts died of a vascular occlusive events considered related to ponatinib Kantarjian et al, J Clin Oncol 32:5s, 2014 (suppl; abstr 7081). Data as of 6 Jan 2014
20 ENESTnd (nilotinib) Cardiovascular Events by 5 Years Nilotinib 300 mg BID (n = 279) Nilotinib 400 mg BID (n = 277) Imatinib 400 mg QD (n = 280) Total, n (%) Y1-4, Y5, n b n c Total, n (%) Y1-4, Y5, n b n c Total, n (%) Y1-4, Y5, n b n c Total patients with CVEs 21 (7.5) (13.4) (2.1) 4 2 Ischemic heart disease 11 (3.9) (8.7) (1.8) 3 2 Ischemic cerebrovascular events 4 (1.4) (3.2) (0.4) 1 0 Peripheral artery disease 7 (2.5) (2.5) Y, year. a All events, regardless of relationship to study drug. b Data cutoff: July 27, 2012 (minimum follow-up of 48 cycles). c Events reported between the 48-cycle and 60-month data cutoffs. CVE, cardiovascular event.
21 PACE: Probability of Arterial Thrombotic Events Risk factors significantly associated with arterial thrombotic AEs: - Older age (p<0.0001) - History of diabetes (p=0.0003) - Higher dose intensity to time of first event (p=0.0009) - History of ischemia (p=0.0087) - Longer time since diagnosis (p=0.0228) - Higher baseline neutrophils (p=0.0466) - Higher baseline platelets (p=0.0276) Each 15-mg reduction in average daily dose intensity is predicted to lead to approximately 33% reduction in the risk of an arterial thrombotic event Includes all patients with baseline data available (N=441); the area shaded in orange represents the 95% CI. Hochhaus, et al. J Clin Oncol ,5s: 7084.
22 Where next?
23
24 5-Year Outcomes by Molecular Response at 3 Months Dasatinib 100 mg OD (n=259) Imatinib 400 mg OD (n=260) BCR-ABL at 3 Months 10% (84%) >10% (16%) P value 10% (64%) >10% (36%) P value Estimated 5-year OS, % Estimated 5-year PFS, % Estimated 5-year TFS, % < < On-study treatment and in follow-up after discontinuation of randomized treatment. TFS, transformation-free survival. Cortes J, et al. Presented at: 2014 Annual Meeting of ASH; San Francisco, CA. Oral presentation.
25 risk benefit drug? dose?
26 Stage 1 Compare first line intervention: Imatinib vs 2 nd generation Stage 2 Identify partial responders (e.g >10% BCR- ABL) early: Switch to ponatinib Stage 3 Identify best responders later Reduce/stop, as in DESTINY Primary endpoint: MR 3 (MMR) at 3 years Secondary: sustained MR 3 on reduced dose/stop EFS, PFS, OS Health Economics, QoL
27 Selective switch for poor response (3, 12, 18 months) Safety optimisation Primary endpoint: 3 years n=500 Imatinib 400 Imatinib 400 QRISK2 R Imatinib 400 Hi Lo Ponatinib 30 Intolerance: Clinical Review Panel Nilotinib 600 Lo Hi Nilotinib 600 Ponatinib 30 Ponatinib 15 if MR3 Other Other Nilotinib 600 Ponatinib 15 if MR3 Aim to reduce and stop (if MR3 for at least 1 year) 1G Group 2G Group n=500 Dasatinib 100 Hi Lo Dasatinib 100 Dasatinib 100
28
29 SPIRIT 3 & CV risk QRISK2 at entry Drug stratification 20% 10yr risk threshold for intervention Lipids HbA1C BP Haematologists pick up, GP manages
30 Selective switch for poor response (3, 12, 18 months) Safety optimisation Primary endpoint: 3 years n=500 Imatinib 400 Imatinib 400 QRISK2 R Imatinib 400 Hi Lo Ponatinib 30 Intolerance: Clinical Review Panel Nilotinib 600 Lo Hi Nilotinib 600 Ponatinib 30 Ponatinib 15 if MR3 Other Other Nilotinib 600 Ponatinib 15 if MR3 Aim to reduce and stop (if MR3 for at least 1 year) 1G Group 2G Group n=500 Dasatinib 100 Hi Lo Dasatinib 100 Dasatinib 100
31
32 CML 2016: benefits & risks Imatinib vs 2 nd generation: Higher rates of PCR response with 2 nd gen No difference in overall survival Marginal difference in progression-free survival Newer TKIs have more/different toxicity Poor understanding of mechanism Balance of risk and benefit; optimal dose? Most (but not all) patients do well on imatinib Who should switch to 2 nd /3 rd line drugs? SPIRIT 3 2 nd gen: maybe more patients can stop or dose reduce? Increasingly cost, risk/benefit will drive choice
33 CML 2016 Risks & benefits Steve O Brien CML Horizons, May 2016
SESSION III: Chronic myeloid leukemia PONATINIB. Gianantonio Rosti, MD, Department of Hematology, University of Bologna, Italy
SESSION III: Chronic myeloid leukemia PONATINIB Gianantonio Rosti, MD, Department of Hematology, University of Bologna, Italy Ponatinib A Pan-BCR-ABL Inhibitor Rationally designed inhibitor of BCR- ABL
More informationDose reduction. What do we know and how we do it in clinical practice. Andreas Hochhaus
Dose reduction. What do we know and how we do it in clinical practice. Andreas Hochhaus Hadera I Oct 2018 Front-line Randomized Trials in CML-CP Trial Drugs References IRIS IM 400 vs IFN/AraC TOPS IM
More informationRole of Second Generation Tyrosine Kinase Inhibitors in Newly Diagnosed CML. GIUSEPPE SAGLIO, MD University of Torino, Italy
Role of Second Generation Tyrosine Kinase Inhibitors in Newly Diagnosed CML GIUSEPPE SAGLIO, MD University of Torino, Italy Outcome in 282 Patients Treated with Imatinib First Line in Hammersmith Hospital
More informationCML: Living with a Chronic Disease
CML: Living with a Chronic Disease Jorge Cortes, MD Chief, CML and AML Sections Department of Leukemia M. D. Anderson Cancer Center Houston, Texas Survival in Early Chronic Phase CML TKI Interferon Chemotherapy
More informationELN Recommendations on treatment choice and response. Gianantonio Rosti, MD, Department of Hematology, University of Bologna, Italy
ELN Recommendations on treatment choice and response Gianantonio Rosti, MD, Department of Hematology, University of Bologna, Italy ELN 2013 Response to Front-line Treatment Baseline 3 months 6 months OPTIMAL
More informationLow doses of tyrosine kinase inhibitors in CML
CML Horizons Conference Warsaw 4-6 May 2018 Low doses of tyrosine kinase inhibitors in CML Delphine Rea, MD, PhD Pôle Hématologie Oncologie Radiothérapie INSERM UMR-1160 Centre Hospitalo-Universitaire
More informationHow I treat high risck CML
Torino, September 14, 2018 How I treat high risck CML Patrizia Pregno Hematology Dept. Citta della Salute e della Scienza Torino Disclosures Advisory Board: Novartis, Pfizer, Incyte Speaker Honoraria:
More informationGuidelines and real World: Management of CML in chronic and advanced phases. Carolina Pavlovsky. FUNDALEU May 2017 Frankfurt
Guidelines and real World: Management of CML in chronic and advanced phases Carolina Pavlovsky. FUNDALEU 26-28 May 217 Frankfurt Some Issues in CML 217 First Line treatment: Imatinib vs 2nd generation
More informationNEW DRUGS IN HEMATOLOGY Bologna, 9-11 May 2016 CHRONIC MYELOID LEUKEMIA STATUS OF THE ART OF TREATMENT.
NEW DRUGS IN HEMATOLOGY Bologna, 9-11 May 2016 CHRONIC MYELOID LEUKEMIA STATUS OF THE ART OF TREATMENT Michele.baccarani@unibo.it Michele BACCARANI, MD Professor of Hematology at the Universities of Trieste,
More informationWhat is the optimal management strategy for younger CP-CML patients with matched, related donors who fail to achieve CCyR
What is the optimal management strategy for younger CP-CML patients with matched, related donors who fail to achieve CCyR after 18 months of imatinib? Second generation TKIs as a bridge to allogeneic SCT
More informationThe concept of TFR (Treatment Free Remission) in CML
The concept of TFR (Treatment Free Remission) in CML Giuseppe Saglio University of Turin, Italy What can we expect today on long-term therapy with TKIs in CML? German CML study IV Relative and overall
More information2 nd Generation TKI Frontline Therapy in CML
2 nd Generation TKI Frontline Therapy in CML Elias Jabbour, M.D. April 212 New York Frontline Therapy of CML in 212 - imatinib 4 mg daily - nilotinib 3 mg BID - dasatinib 1 mg daily Second / third line
More information2nd generation TKIs to first line therapy
New Horizons 2011 Newly diagnosed CML moving 2nd generation TKIs to first line therapy Gianantonio Rosti Dept. Of Hematology and Oncology St. Orsola-Malpighi University Hospital Bologna (Italy) GIMEMA
More informationStopping Treatment in CML and dose reduction in clinical practice: Can we do it safely? YES WE CAN!
Stopping Treatment in CML and dose reduction in clinical practice: Can we do it safely? YES WE CAN! Dragana Milojković The Hammersmith Hospital, London, UK Leukemic burden Current Aim of TKI therapy Molecular
More informationAGGIORNAMENTI IN EMATOLOGIA Faenza, 7 Giugno 2018 LMC: ALGORITMI TERAPEUTICI ATTUALI E IL PROBLEMA DELLA RESISTENZA.
AGGIORNAMENTI IN EMATOLOGIA Faenza, 7 Giugno 2018 LMC: ALGORITMI TERAPEUTICI ATTUALI E IL PROBLEMA DELLA RESISTENZA Michele.Baccarani@unibo.it EUROPEAN LEUKEMIANET 2013 (Blood 2013;122:885 892). RESPONSE
More informationExecutive summary Overview
Executive summary Overview In this appraisal, we have demonstrated that dasatinib is clinically more effective, as well as more cost effective, than imatinib, the current standard of care. In the pivotal
More informationIRIS 8-Year Update. Management of TKI Resistance Will KD mutations matter? Sustained CCyR on study. 37% Unacceptable Outcome 17% 53% 15%
Management of TKI Resistance Will KD mutations matter? IRIS 8-Year Update 17% 53% 5% 15% 37% Unacceptable Outcome No CCyR Lost CCyR CCyR Other 3% 7% Safety Lost-regained CCyR Sustained CCyR on study Deininger
More informationCML David L Porter, MD University of Pennsylvania Medical Center Abramson Cancer Center CML Current treatment options for CML
1 CML 2012 LLS Jan 26, 2012 David L Porter, MD University of Pennsylvania Medical Center Abramson Cancer Center CML 2012 Current treatment options for CML patients Emerging therapies for CML treatment
More informationContemporary and Future Approaches in CML. Emory Meeting; Sea Island August 2014 Hagop Kantarjian, M.D.
Contemporary and Future Approaches in CML Emory Meeting; Sea Island August 2014 Hagop Kantarjian, M.D. 1 CML. Historical vs. Modern Perspective Parameter Historical Modern Course Fatal Indolent Prognosis
More informationHull and East Yorkshire and North Lincolnshire NHS Trusts Haematology Multidisciplinary Team Guideline and Pathway. Chronic Myeloid Leukaemia
Hull and East Yorkshire and North Lincolnshire NHS Trusts Haematology Multidisciplinary Team Guideline and Pathway Chronic Myeloid Leukaemia 1 BACKGROUND The Hull and North Lincolnshire Haematology Multidisciplinary
More information10 YEARS EXPERIENCE OF TYROSINE KINASE INHIBITOR THERAPY FOR CML IN OXFORD
10 YEARS EXPERIENCE OF TYROSINE KINASE INHIBITOR THERAPY FOR CML IN OXFORD Dalia Khan 1, Noemi Roy 1, Vasha Bari 1, Grant Vallance 1, Helene Dreau 1, Timothy Littlewood 1, Andrew Peniket 1, Paresh Vyas
More informationSummary 1. Comparative effectiveness of ponatinib
Cost-effectiveness of ponatinib (Iclusig ) as indicated for adult patients with: (i) CP-, AP-, or BP- chronic myeloid leukaemia (CML) who are resistant to dasatinib or nilotinib; who are intolerant to
More informationHOW I TREAT CML. 4. KONGRES HEMATOLOGOV IN TRANSFUZIOLOGOV SLOVENIJE Z MEDNARODNO UDELEŽBO Terme Olimia, Podčetrtek,
HOW I TREAT CML 4. KONGRES HEMATOLOGOV IN TRANSFUZIOLOGOV SLOVENIJE Z MEDNARODNO UDELEŽBO Terme Olimia, Podčetrtek, 12. - 14. april, 2012 Gianantonio Rosti Dpt of Hematology and Oncological Sciences S.
More informationLa terapia della LMC: è possibile guarire senza trapianto? Fabrizio Pane
La terapia della LMC: è possibile guarire senza trapianto? Fabrizio Pane What could be the concept of Cure in CML? Sustained DMR with or without TKI therapy And 100% CML-related survival And QoL comparable
More informationThe BCR-ABL1 fusion. Epidemiology. At the center of advances in hematology and molecular medicine
At the center of advances in hematology and molecular medicine Philadelphia chromosome-positive chronic myeloid leukemia Robert E. Richard MD PhD rrichard@uw.edu robert.richard@va.gov Philadelphia chromosome
More informationPonatinib for treating chronic myeloid leukaemia and acute lymphoblastic leukaemia
Ponatinib for treating chronic myeloid leukaemia and acute lymphoblastic leukaemia Single Technology Appraisal 2 nd Committee meeting: 16 March 2017 Committee C FOR PUBLIC Key issues Absence of direct
More informationOxford Style Debate on STOPPING Treatment.
Oxford Style Debate on STOPPING Treatment. This house believes that there are good reasons NOT to stop CML treatment. It should be done within clinical trials, OR only in expert centers where frequent,
More informationChronic Myeloid Leukemia A Disease of Young at Heart but Not of Body
Chronic Myeloid Leukemia A Disease of Young at Heart but Not of Body Jeffrey H Lipton, PhD MD FRCPC Staff Physician, Princess Margaret Cancer Centre Professor of Medicine University of Toronto POGO November,
More informationCML: Yesterday, Today and Tomorrow. Jorge Cortes, MD Chief CML Section Department of Leukemia The University of Texas, M.D. Anderson Cancer Center
CML: Yesterday, Today and Tomorrow Jorge Cortes, MD Chief CML Section Department of Leukemia The University of Texas, M.D. Anderson Cancer Center Five Years of Signal Transduction Inhibition The Beginning
More informationCML and Future Perspective. Hani Al-Hashmi, MD
CML and Future Perspective Hani Al-Hashmi, MD Objectives Learning from CML history Outcome of interest to clinician Patient and community interest!! Learning from CML history Survival Probability (All
More informationSupplementary Online Content
Supplementary Online Content Douxfils J, Haguet H, Mullier F, Chatelain C, Graux C, Dogné J-M. Use of BCR-ABL tyrosine kinase inhibitors in chronic myeloid leukemia: a systematic review and metaanalysis
More informationRESEARCH ARTICLE. Introduction. Methods Wiley Periodicals, Inc.
BCR/ABL level at 6 months identifies good risk CML subgroup after failing early molecular response at 3 months following imatinib therapy for CML in chronic phase AJH Dennis (Dong Hwan) Kim, 1 * Nada Hamad,
More informationTreatment free remission in CML: from the concept to practice. François-Xavier Mahon. Cancer Center Bordeaux Université Bordeaux, France
Treatment free remission in CML: from the concept to practice François-Xavier Mahon Cancer Center Bordeaux Université Bordeaux, France CML is a model 1960 1970 1980 1990 2000 2010 Philadelphia chromosome
More informationEvaluating Cost-Effectiveness in Later-line Chronic Myeloid Leukemia (CML): Ponatinib in the Third-Line Treatment of CML in Canada
Evaluating Cost-Effectiveness in Later-line Chronic Myeloid Leukemia (CML): Ponatinib in the Third-Line Treatment of CML in Canada Jeffrey H. Lipton, Sergio Iannazzo, Silvia Chiroli, Lisa McGarry 06 CADTH
More informationNew drugs in first-line therapy
New drugs in first-line therapy Gianantonio Rosti Dept of Hematology and Oncology Seràgnoli, Bologna University (Italy) GIMEMA (Gruppo Italiano Malattie Ematologiche dell Adulto) CML WORKING PARTY IRIS
More informationNEW DRUGS IN HEMATOLOGY
NEW DRUGS IN HEMATOLOGY BOLOGNA, 15-17 April 2013 TYROSINE KINASE INHIBITORS IN CHRONIC MYELOID LEUKEMIA MICHELE BACCARANI michele.baccarani@unibo.it Historic Development of CML Therapy Palliative Therapy
More informationManagement of CML in blast crisis. Lymphoma Tumor Board November 27, 2015
Management of CML in blast crisis Lymphoma Tumor Board November 27, 2015 Chronic Phase CML - 2. Peter Maslak, ASH Image Bank 2011; 2011-2455 Copyright 2011 American Society of Hematology. Copyright restrictions
More informationContemporary and Future Approaches in Management of CML. Disclosures
Winship Cancer Institute of Emory University Contemporary and Future Approaches in Management of CML Hagop Kantarjian, MD Chairman and Professor, Department of Leukemia University of Texas M. D. Anderson
More informationCML 301 SOME INTRODUCTION INTO CML, CML SCIENCE, DRUG DEVELOPMENT AND INFORMATION RESOURCES. by Sarunas Narbutas Jan Geissler.
CML 301 SOME INTRODUCTION INTO CML, CML SCIENCE, DRUG DEVELOPMENT AND INFORMATION RESOURCES by Sarunas Narbutas Jan Geissler 4 May 2018 CML 101 / BASICS: UNDERSTANDING THE DISCUSSIONS IN CML SESSIONS What
More informationEUROPEAN LEUKEMIANET RECOMMENDATIONS FOR CHRONIC MYELOID LEUKEMIA
EUROPEAN LEUKEMIANET RECOMMENDATIONS FOR CHRONIC MYELOID LEUKEMIA SAN DIEGO, 11 DECEMBER 2011 AMSTERDAM, 14 JUNE 2012 BALTIMORE, 20 SEPTEMBER 2012 ATLANTA, 6 DECEMBER 2012 ELN, CML Panel Jane Apperley
More informationDoes Generic Imatinib Change the Treatment Approach in CML?
Does Generic Imatinib Change the Treatment Approach in CML? Jerald P. Radich, MD Fred Hutchinson Cancer Research Center/ Seattle Cancer Care Alliance NCCN.org For Clinicians NCCN.org/patients For Patients
More informationWhat is New in CML in Hagop Kantarjian, M.D. February 2011
What is New in CML in 2011 Hagop Kantarjian, M.D. February 2011 1 CML. Historical vs. Modern Perspective Parameter Historical Modern Course Fatal Indolent Prognosis Poor Excellent 10-yr survival 10% 84-90%
More informationStarting & stopping therapy in Chronic Myeloid Leukemia: What more is needed? Richard A. Larson, MD University of Chicago March 2019
Starting & stopping therapy in Chronic Myeloid Leukemia: What more is needed? Richard A. Larson, MD University of Chicago March 2019 Disclosures Richard A. Larson, MD Research funding to the University
More informationPonatinib in chronic myeloid leukaemia (CML) 2
Resolution by the Federal Joint Committee on an amendment to the Pharmaceutical Directive (AM-RL): Appendix XII Resolutions on the benefit assessment of pharmaceuticals with new active ingredients, in
More informationWhat is New in CML Jorge Cortes, MD Chief, CML and AML Sections Department of Leukemia MD Anderson Cancer Center Houston, Texas
What is New in CML 2018 Jorge Cortes, MD Chief, CML and AML Sections Department of Leukemia MD Anderson Cancer Center Houston, Texas Final Results CML-IV Molecular Response with Imatinib 1538 pts newly
More informationWelcome and Introductions
Living with Chronic Myeloid Leukemia Welcome and Introductions Living with Chronic Myeloid Leukemia Living with Chronic Myeloid Leukemia (CML) Neil P. Shah, MD, PhD Edward S. Ageno Distinguished Professor
More informationCML Clinical Case Scenario
CML Clinical Case Scenario Neil Shah, MD, PhD Edward S. Ageno Distinguished Professor in Hematology/Oncology Leader, Hematopoietic Malignancies Program Helen Diller Family Comprehensive Cancer Center at
More informationpan-canadian Oncology Drug Review Final Clinical Guidance Report Ponatinib (Iclusig) for Chronic Myeloid Leukemia / Acute Lymphoblastic Leukemia
pan-canadian Oncology Drug Review Final Clinical Guidance Report Ponatinib (Iclusig) for Chronic Myeloid Leukemia / Acute Lymphoblastic Leukemia October 1, 2015 DISCLAIMER Not a Substitute for Professional
More informationChronic Myeloid Leukaemia
Chronic Myeloid Leukaemia Molecular Response: What is really important? Jeff Szer The Royal Melbourne Hospital PROBABILITY, % PROBABILITY OF SURVIVAL AFTER MYELOABLATIVE TRANSPLANTS FOR CML IN CHRONIC
More informationAccepted Manuscript. Improving Outcomes in Chronic Myeloid Leukemia Over Time in the Era of Tyrosine Kinase Inhibitors. Pradnya Chopade, Luke P.
Accepted Manuscript Improving Outcomes in Chronic Myeloid Leukemia Over Time in the Era of Tyrosine Kinase Inhibitors Pradnya Chopade, Luke P. Akard PII: S2152-2650(18)30343-4 DOI: 10.1016/j.clml.2018.06.029
More informationat least one dose interruption. perc noted the manufacturer of ponatinib issued a dose reduction recommendation in the PACE study; however, there are currently no data on the optimal starting dose for
More informationJuan Luis Steegmann Hospital de la Princesa. Madrid. JL Steegmann
Juan Luis Steegmann Hospital de la Princesa. Madrid. Juan Luis Steegmann Hospital de la Princesa. Madrid No rush,at least in Chronic Phase Blast Phase*: SCT asap, after restablishing CP with TKI Accelerated
More informationA 34-year old women came because of abdominal discomfort. Vital sign was stable. Spleen tip was palpable.
1 Case 1 A 34-year old women came because of abdominal discomfort. Vital sign was stable. Spleen tip was palpable. CBC and bone marrow aspiration and biopsy were done. Chromosome study showed she had t(9;22)
More informationBMS Satellite Symposium
ICKSH 2018 BMS Satellite Symposium Emerging Trends in CML Management CHAIRMAN The Head of Catholic Hematology Hospital The Director of the Catholic Leukemia Research Institute at the Catholic University
More informationStopping treatment how much we understand about mechanisms to stop successfully today, and where are the limits? Andreas Hochhaus
Stopping treatment how much we understand about mechanisms to stop successfully today, and where are the limits? Andreas Hochhaus Frankfurt I 27.5.2017 Aims of CML Therapy Leukemia cells >10 12 CHR 10
More informationCML Update 2016 Arthur 2016
CML Update 2016 Chronic Myeloid Leukemia Splenomegaly CML (3 phase disease) Increased white cells Malignant proliferation of myeloid white cells Initially mature cells a) chronic phase of disease Evolution
More informationPost ASH Actualités LMC
Post ASH 2014 - Actualités LMC Actualités de première ligne LMC PC ENESTnd (6 ans) Dasision (5 ans) EPIC Spirit France (5 ans) Spirit 2 UK (5 ans) ENESTnd: Mise à jour à 6 ans Design = 846 ults with wly
More information1 Educational session salient points. Tim Hughes, Vivian Oehler and Rick Van Etten. Tim - Imatinib is a less toxic drug than what we are seeing with
1 Educational session salient points. Tim Hughes, Vivian Oehler and Rick Van Etten. Tim - Imatinib is a less toxic drug than what we are seeing with both Nilotinib and Dasatinib. Nilotinib for the cardio
More informationI nuovi guariti? La malattia minima residua nella leucemia mieloide cronica. Fabrizio Pane
I nuovi guariti? La malattia minima residua nella leucemia mieloide cronica Fabrizio Pane What could be the concept of Cure in CML? Sustained DMR with or without TKI therapy And 100% CML-related survival
More informationMeta-analysis: Methodology
Meta-analysis: Methodology Example: Assessment of cardiovascular safety profile of new generation BCR-ABL TKIs in patients with CML Haguet Hélène 04/03/2016 Meta-analysis = statistical combination of results
More informationStopping TKI s in CML- Are we There Yet? Joseph O. Moore, MD Duke Cancer Institute
Stopping TKI s in CML- Are we There Yet? Joseph O. Moore, MD Duke Cancer Institute Natural History of CML Accumulation of immature myeloid cells New cytogenetic changes Chronic Phase Accelerated Phase
More informationMolecular monitoring of CML patients
EHA, Education Session, CML Stockholm, 14 June 2013 Molecular monitoring of CML patients Martin C. Müller Medical Faculty Mannheim Ruprecht-Karls-University Heidelberg Mannheim, Germany Disclosures Research
More informationreconsideration of the perc Initial Recommendation, perc noted that a RCT would likely not be feasible beyond the second-line setting for patients in whom other TKI therapy is not appropriate because of
More informationDati sulla sospensione della terapia
Leucemia Mieloide Cronica Dati sulla sospensione della terapia Gianantonio Rosti, Bologna BCR-ABL Loading in CML Patients 100% 10% 1% MMR MR 4 MR 4.5 STIM study design N=100 Start Imatinib CMR Sustained
More informationCML HORIZONS 101 AND CML 101
CML HORIZONS 101 AND CML 101 by Pat Garcia-Gonzalez, USA May 1, 2015 Barcelona, Spain Goals of this Session Everything you ever wanted to know and were afraid of asking Help you navigate the conference
More informationHistory of CML Treatment
History of CML Treatment Eduardo Olavarria No conflict of interest Lisbon, 20th March 2018 #EBMT18 www.ebmt.or What is CML? The mystery of chronic myeloid leukaemia Chronic myeloid leukaemia Often diagnosed
More informationChronic myeloid leukemia (CML) Warunsuda Sripakdee, BCOP,BCP Prince of Songkla University
Chronic myeloid leukemia (CML) 1 Warunsuda Sripakdee, BCOP,BCP Prince of Songkla University Hematologic malignancies CML ALL AML 2 CML CD34+ results from an acquired mutation that affects hematopoietic
More informationCML UPDATE 2018 DAVID S. SNYDER, M.D. MARCH
CML UPDATE 2018 DAVID S. SNYDER, M.D. MARCH 15, 2018 Click to edit Master Presentation Date DISCLOSURES I have nothing to disclose 2001 2016 Loss in expectation of life of patients with chronic myeloid
More informationNew drugs and trials. Andreas Hochhaus
New drugs and trials. Andreas Hochhaus Hadera I Oct 2018 Introduction ABL001 is a potent, specific inhibitor of BCR-ABL1 with a distinct allosteric mechanism of action BCR-ABL1 Protein Binds a distinct
More informationpan-canadian Oncology Drug Review Final Clinical Guidance Report Bosutinib (Bosulif) for Chronic Myelogenous Leukemia April 21, 2015
pan-canadian Oncology Drug Review Final Clinical Guidance Report Bosutinib (Bosulif) for Chronic Myelogenous Leukemia April 21, 2015 DISCLAIMER Not a Substitute for Professional Advice This report is primarily
More informationARIAD Pharmaceuticals, Inc.
ARIAD Pharmaceuticals, Inc. June 8, 2016 David Sachs Non-small cell lung cancer 1 ARIAD clinical trial patient Some of the statements in this presentation constitute forward looking statements under the
More informationBuilding Shareholder Value
Building Shareholder Value June 4, 2014 Jefferies Healthcare Conference Tim Clackson, Ph.D. Hans Loland P r e s i d e n t o f R & D, C h i e f S c i e n t i f i c O f f i c e r with wife Cynthia A R I
More informationBCCA Protocol Summary for Treatment of Chronic Myeloid Leukemia and Ph+ Acute Lymphoblastic Leukemia Using PONAtinib
BCCA Protocol Summary for Treatment of Chronic Myeloid Leukemia and Ph+ Acute Lymphoblastic Leukemia Using PONAtinib Protocol Code Tumour Group Contact Physician ULKCMLP Leukemia Dr. Donna Forrest ELIGIBILITY:
More informationMolecular pathogenesis of CML: Recent insights
Napoli 24 gennaio 2012 Molecular pathogenesis of CML: Recent insights Giuseppe Saglio University of Turin CML Biology CML Clinical practice MILESTONES IN MOLECULAR BIOLOGY OF CML 1960 - Nowell P.C. & Hungerford
More informationCML: Lead team presentation Ponatinib for treating chronic myeloid leukaemia [ID671] - STA
PUBLIC OBSERVER SLIDES CML: Lead team presentation Ponatinib for treating chronic myeloid leukaemia [ID671] - STA 1 st Appraisal Committee meeting Background and Clinical Effectiveness Committee C Lead
More informationPonatinib Withdrawal Update
Hello. This is Dr. Stuart Goldberg from the Leukemia Division at the John Theurer Cancer Center at Hackensack University Medical Center in Hackensack, New Jersey. I am speaking on behalf of ManagingCML.com
More informationPractical Guidance for the Management of CML in 2016
Practical Guidance for the Management of CML in 2016 Neil Shah, MD, PhD Edward S. Ageno Distinguished Professor in Hematology/Oncology Leader, Hematopoietic Malignancies Program Helen Diller Family Comprehensive
More informationCML TREATMENT GUIDELINES
CML TREATMENT GUIDELINES INITIAL INVESTIGATION Propose enrolment in the CML Registry of the CML-MPN Quebec Research Group. Medical history : Question for cardio-respiratory disorders, diabetes, pancreatitis,
More informationState of the Art Therapy and Monitoring of CML Hagop Kantarjian, M.D. Grand Rounds UT Southwestern. October 28, 2010
State of the Art Therapy and Monitoring of CML - 2010 Hagop Kantarjian, M.D. Grand Rounds UT Southwestern October 28, 2010 1 CML. Historical vs. Modern Perspective Parameter Historical Modern Course Fatal
More informationTechnology appraisal guidance Published: 24 August 2016 nice.org.uk/guidance/ta401
Bosutinib for previously treated chronic myeloid leukaemia Technology appraisal guidance Published: 24 August 2016 nice.org.uk/guidance/ta401 NICE 2018. All rights reserved. Subject to Notice of rights
More informationPATIENTS IN FOCUS: WHAT S RELEVANT FOR CHRONIC MYELOID LEUKAEMIA AND PHILADELPHIA CHROMOSOME-POSITIVE ACUTE LYMPHOBLASTIC LEUKAEMIA?
PATIENTS IN FOCUS: WHAT S RELEVANT FOR CHRONIC MYELOID LEUKAEMIA AND PHILADELPHIA CHROMOSOME-POSITIVE ACUTE LYMPHOBLASTIC LEUKAEMIA? This satellite symposium took place on 22 nd June 2017 as part of the
More informationChronic Myeloid Leukemia Outlook: The Future of CML Therapy
Chronic Myeloid Leukemia Outlook: The Future of CML Therapy Neil Shah, MD PhD Edward S. AgenoDistinguished Professor in Hematology/Oncology UCSF School of Medicine San Francisco, California Progression
More informationPath to Value and Profitability
Path to Value and Profitability June 4, 2015 Tim Clackson, Ph.D. President of R&D, Chief Scientific Officer ARIAD Pharmaceuticals, Inc. Elsa So Non-small cell lung cancer ARIAD clinical trial patient Some
More informationAbstracts and notes on CML presentations 1 ASH 2012 Atlanta
Abstracts and notes on CML presentations 1 ASH 2012 Atlanta Steve O Brien, Newcastle University 1 Highlights... 1 2 Plenary session [3]... 4 3 CML Therapy I [163-168]... 4 4 CML Therapy II [913-918]...
More information15 th Annual Miami Cancer Meeting
15 th Annual Miami Cancer Meeting CLL and CML Mohamed A. Kharfan-Dabaja, MD, MBA, FACP Director, Blood and Marrow Transplantation and Cellular Therapies Mayo Clinic Jacksonville, FL 15 th Annual Miami
More informationChronic Myeloid Leukemia: What more is needed? Richard A. Larson, MD University of Chicago March 2018
Chronic Myeloid Leukemia: What more is needed? Richard A. Larson, MD University of Chicago March 2018 Disclosures Richard A. Larson, MD Research funding to the University of Chicago: Astellas Celgene Daiichi
More informationIS MUTATION ANALYSIS OF BCR-ABL OF ANY VALUE IN CLINICAL MANAGEMENT OF CML PATIENTS? David Marin, Imperial College London
IS MUTATION ANALYSIS OF BCR-ABL OF ANY VALUE IN CLINICAL MANAGEMENT OF CML PATIENTS? David Marin, Imperial College London Tell me generals, are we politicians necessary? I have to admit defeat before starting
More informationIs there a best TKI for chronic phase CML?
MANAGING TYPICAL AND ATYPICAL CHRONIC MYELOID LEUKEMIA Is there a best TKI for chronic phase CML? Richard A. Larson 1 1 Section of Hematology/Oncology, Department of Medicine, and Comprehensive Cancer
More informationDAVID S. SNYDER, M.D.
CML UPDATE 2019 DAVID S. SNYDER, M.D. MARCH 21,2019 Click to edit Master Presentation Date Disclosures I do not have anything to disclose 2001 2016 Loss in expectation of life of patients with chronic
More informationEVI-1 oncogene expression predicts survival in chronic phase CML patients resistant to imatinib
EVI-1 oncogene expression predicts survival in chronic phase CML patients resistant to imatinib Mustafa Daghistani Department of Haematology, Imperial College London at Hammersmith Hospital, Du Cane Road,
More information517 Spirit 2: An NCRI Randomised Study Comparing Dasatinib with Imatinib in Patients with Newly Diagnosed CML
517 Spirit 2: An NCRI Randomised Study Comparing Dasatinib with Imatinib in Patients with Newly Diagnosed CML https://ash.confex.com/ash/2014/webprogram/paper66809.html Objective. SPIRIT 2 is the largest
More informationOutlook CML 2016: What is being done on the way to cure
New Horizons 2011 Outlook CML 2016: What is being done on the way to cure Gianantonio Rosti Dept. Of Hematology and Oncology St. Orsola-Malpighi University Hospital Bologna (Italy) GIMEMA CML Working Party
More informationCHRONIC MYELOID LEUKEMIA (CML) Managing the Long and the Short of It
CHRONIC MYELOID LEUKEMIA (CML) Managing the Long and the Short of It Jeffrey H Lipton PhD MD Princess Margaret Cancer Centre Professor of Medicine University of Toronto CAGPO Annual Conference St. John
More informationTKIs ( Tyrosine Kinase Inhibitors ) Mechanism of action and toxicity in CML Patients. Moustafa Sameer Hematology Medical Advsior,Novartis oncology
TKIs ( Tyrosine Kinase Inhibitors ) Mechanism of action and toxicity in CML Patients Moustafa Sameer Hematology Medical Advsior,Novartis oncology Introduction In people with chronic myeloid leukemia, A
More informationCML: Role of combination treatments, Interferon and immunotherapy in CML
CML: 2017 Role of combination treatments, Interferon and immunotherapy in CML Andreas Burchert Philipps Universität Marburg Universitätsklinikum Gießen und Marburg GmbH Key Developments that will Change
More informationNCCP Chemotherapy Protocol. Ponatinib Therapy
INDICATIONS FOR USE: INDICATION Treatment of adult patients with chronic phase, accelerated phase, or blast phase chronic myeloid leukaemia (CML) who are resistant to dasatinib or nilotinib; who are intolerant
More informationStudy Design and Endpoints
Complete Molecular Response (CMR) Rate With Nilotinib in Patients With CML-CP Without CMR After 2 Years on Imatinib: Preliminary Results From the Randomized ENESTcmr Trial Timothy P. Hughes, Jeffrey H.
More informationPFIZER INC. These results are supplied for informational purposes only. Prescribing decisions should be made based on the approved package insert.
Public Disclosure Synopsis Protocol 316A4-223 (B18717) 11 October 216 Final PFIZER INC. These results are supplied for informational purposes only. Prescribing decisions should be made based on the approved
More informationAllogeneic SCT for. 1st TKI. Vienna Austria. Dr. Eduardo Olavarría Complejo Hospitalario de Navarra
The International Congress on Controversies in Stem Cell Transplantation and Cellular Therapies (COSTEM) Berlin, Germany September 8-11, 2011 Vienna Austria Allogeneic SCT for CML Allogeneic after failure
More informationImpact of Age on Efficacy and Toxicity of Nilotinib in Patients With Chronic Myeloid Leukemia in Chronic Phase (CML-CP): ENEST1st Sub-Analysis
Impact of Age on Efficacy and Toxicity of Nilotinib in Patients With Chronic Myeloid Leukemia in Chronic Phase (CML-CP): ENEST1st Sub-Analysis Abstract 479 Giles FJ, Rea D, Baccarani M, Cross NCP, Steegmann
More information