mds and mpd ash 2013 n.
Download
Skip this Video
Loading SlideShow in 5 Seconds..
MDS and MPD ASH 2013 PowerPoint Presentation
Download Presentation
MDS and MPD ASH 2013

Loading in 2 Seconds...

play fullscreen
1 / 50

MDS and MPD ASH 2013 - PowerPoint PPT Presentation


  • 202 Views
  • Uploaded on

MDS and MPD ASH 2013. Katherine Walsh MD Katherine.Walsh@osumc.edu . No conflicts of interest to disclose. Off-label use of: azacitidine , vorinostat, and lenalidomide. Objectives. To discuss new insights into the diagnosis of MDS and MPD focusing on new genomic analyses

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'MDS and MPD ASH 2013' - sheera


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
mds and mpd ash 2013

MDS and MPDASH 2013

Katherine Walsh MD

Katherine.Walsh@osumc.edu

No conflicts of interest to disclose.

Off-label use of: azacitidine, vorinostat, and lenalidomide

objectives
Objectives
  • To discuss new insights into the diagnosis of MDS and MPD focusing on new genomic analyses
  • To discuss updates on current treatment options and new treatment strategies in development for MDS and MPD
  • To discuss new agents in development for MDS and MPD
abstract 521 landscape of genetic lesions in 944 patients with myelodysplastic syndromes

Abstract 521Landscape Of Genetic Lesions In 944 Patients With Myelodysplastic Syndromes

Yasunobu Nagata1,2, Vera Grossmann3, Yusuke Okuno1, Ulrike Bacher3, Genta Nagae4, Susanne Schnittger3, Yusuke Shiozawa1,2, Ayana Kon1,2, Tamara Alpermann3, Kenichi Yoshida1,2, Masashi Sanada1,2, Andreas Roller3, Niroshan Nadarajah3, Yuichi Shiraishi5, Kenichi Chiba6, Hiroko Tanaka6, H.Phillip Koeffler7,8, Hans-Ulrich Klein9, Martin Dugas9, Alexander Kohlmann3, Satoru Miyano5,6, Claudia Haferlach3, Hiroyuki Aburatani4, Wolfgang Kern3, Seishi Ogawa1,2 , Torsten Haferlach3

1Cancer Genomics Project, Gr­aduate School of Medicine, The University of Tokyo, Tokyo, Japan;

2Department of Pathology and Tumor Biology, Kyoto University, Kyoto, Japan.

3MLL Munich Leukemia Laboratory, Munich, Germany; 4Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan; 5Laboratory of Sequence Data Analysis, Human Genome Center, 6Laboratory of DNA Information Analysis, Institute of Medical Science, The University of Tokyo, Tokyo, Japan; 7Hematology/Oncology, Cedars-Sinai Medical Center; 8National University of Singapore, Cancer Science Institute of Singapore, 9Department of Medical Informatics and Biomathematics, University of Münster, Münster, Germany

slide4

Landscape of gene mutations in MDS

Splicing factor mutations were largely mutually exclusive

The distribution of other mutations also does not seem to be random

slide5

Frequency of gene mutations involved in common functional pathways

The most frequent target was RNA splicing, with mutations observed in as many as 64% of cases

conclusions from abstract 386
Conclusions from Abstract #386
  • Azacitidine and vorinostat can be safely combined in patients with MDS with the following toxicities reported:
    • Fatigue during the first 3 cycles (8-16% per cohort)
    • GI toxicity including vomiting, diarrhea, and dehydration (8% of each of the cohorts)
  • The combination appeared well tolerated over multiple cycles without cumulative toxicity
slide11

Abstract 388Outcome of Patients (pts) with Low and Intermediate-1 Risk Myelodysplastic Syndrome (MDS) After Hypomethylating Agent (HMA) Failure: A Report on Behalf of the MDS Clinical Research Consortium

E Jabbour, G Garcia-Manero, P Strati, NH. Al Ali,

AMishra, E Padron, J Lancet, J Bryan, H Prescott, D Steensma, MA. Sekeres, GJ. Roboz, AF. List, H Kantarjian, RS. Komrokji

slide13

Factors Associated with Progression into Higher-Risk Disease

MDGSS= MDACC Global Scoring System; Kantrajian. Cancer 2008;113:1351-61

LRMDSS= Low Risk MDACC Scoring System; Garcia-Manero. Leukemia 2008;22:538-43

dual inhibition of p38 and tie2 by arry 614
Dual Inhibition of p38 and Tie2 by ARRY-614

Tie2 in MDS – Emerging Target

p38 MAPK in MDS

Stress/Inflammatory Stimuli (Cytokines, Hypoxia, FasL)

Ang-2

Ang-1

TNF-α, IL-6, Chemokines

Decreased RBC, WBC, platelets

p38

Apoptosis

Pleiotropic effectson Progenitors and AML blasts

  • Dysregulated, may be a survival factor for AML blast
  • Increased signaling associated with poor prognosis
  • Major regulator of the cellular pathways which sense stress
  • Over-activated, leading to inappropriate production of myelosuppressive cytokines
arry 614 reduces phospho p38 in patient bone marrow
ARRY-614 Reduces phospho-p38 in Patient Bone Marrow

Representative Image

Cycle 2

Screening

Paired t test, P <0.05

% phospho-p38 (+) cells

15.2 % p-p38 (+) cells

2.3 % p-p38 (+) cells

Aperio whole slide scanning and scoring performed by Flagship Biosciences

*Screening

n=30†

Cycle 2

n=30†

*Sample collected prior to the first dose of ARRY-614

†Number of pts for whom bone marrow samples available at screening and cycle 2

arry 614 responses
ARRY-614: Responses
  • Overall, durable HI observed in 14 of 71 evaluable patients (20%) as of 31 Oct cut-off date.
  • Responses seen in each of the dose cohorts.
mds summary
MDS Summary
  • The genetic landscape described in a large cohort of MDS patients is potentially clinically relevant for diagnosis and prognosis.
  • For untreated MDS, clinical trials updates showed that combination of azacitidine and vorinostat may be better than azacitidine alone.
  • Low and intermediate risk MDS who fail hypomethylator therapy are in need of better treatments and the novel agent ARRY-614 shows signs of activity in early trial updates.
mpd overview
MPD Overview
  • Two late-breaking abstracts identified CALR mutations in JAK2 wild-type patients and these results were subsequently published in the NEJM.
  • Long-term follow-up data was presented for the COMFORT-1 study with ruxolitinib.
  • In CML, the preliminary results of patients who stopped imatinib in the STIM2 study were presented.
slide20

Original ArticleSomatic Mutations of Calreticulin in Myeloproliferative Neoplasms

Thorsten Klampfl, Ph.D., Heinz Gisslinger, M.D., Ashot S. Harutyunyan, M.D., Ph.D., Harini Nivarthi, Ph.D., Elisa Rumi, M.D., Jelena D. Milosevic, M.Sc., Nicole C.C. Them, M.Sc., Tiina Berg, B.Sc., Bettina Gisslinger, M.Sc., Daniela Pietra, Ph.D., Doris Chen, Ph.D., Gregory I. Vladimer, Ph.D., Klaudia Bagienski, M.Sc., Chiara Milanesi, M.Sc., Ilaria Carola Casetti, M.D., Emanuela Sant'Antonio, M.D., Virginia Ferretti, Ph.D., Chiara Elena, M.D., Fiorella Schischlik, M.Sc., Ciara Cleary, M.Sc., Melanie Six, B.Sc., Martin Schalling, M.Sc., Andreas Schönegger, M.Sc., Christoph Bock, Ph.D., Luca Malcovati, M.D., Cristiana Pascutto, Ph.D., Giulio Superti-Furga, Ph.D., Mario Cazzola, M.D., and Robert Kralovics, Ph.D.

N Engl J Med

Volume 369(25):2379-2390

December 19, 2013

slide21

Frequency of CALR Mutations in Myeloid Neoplasms.

Klampfl T et al. N Engl J Med 2013;369:2379-2390

clinical features of patients with calr mutations
Clinical Features of Patients with CALR mutations

Klampfl T et al. N Engl J Med 2013;369:2379-2390.

slide24

Original ArticleSomatic CALR Mutations in Myeloproliferative Neoplasms with Nonmutated JAK2

J. Nangalia, C.E. Massie, E.J. Baxter, F.L. Nice, G. Gundem, D.C. Wedge, E. Avezov, J. Li, K. Kollmann, D.G. Kent, A. Aziz, A.L. Godfrey, J. Hinton, I. Martincorena, P. Van Loo, A.V. Jones, P. Guglielmelli, P. Tarpey, H.P. Harding, J.D. Fitzpatrick, C.T. Goudie, C.A. Ortmann, S.J. Loughran, K. Raine, D.R. Jones, A.P. Butler, J.W. Teague, S. O'Meara, S. McLaren, M. Bianchi, Y. Silber, D. Dimitropoulou, D. Bloxham, L. Mudie, M. Maddison, B. Robinson, C. Keohane, C. Maclean, K. Hill, K. Orchard, S. Tauro, M.-Q. Du, M. Greaves, D. Bowen, B.J.P. Huntly, C.N. Harrison, N.C.P. Cross, D. Ron, A.M. Vannucchi, E. Papaemmanuil, P.J. Campbell, and A.R. Green

N Engl J Med

Volume 369(25):2391-2405

December 19, 2013

landscape of 151 mpn patients
Landscape of 151 MPN patients
  • 97% of patients had a mutation in either JAK2, MPL, or CALR
  • These mutations were mutually exclusive
  • Clinically relevant for diagnosis and as a potential future treatment target

Nangalia, J et al. N Engl J Med 2013;369:2391-2405.

slide26

Long-Term Outcomes of Ruxolitinib Therapy in Patients with Myelofibrosis: 3-Year Update From COMFORT-I

Srdan Verstovsek,1Ruben A. Mesa,2 Jason Gotlib,3 Richard S. Levy,4Vikas Gupta,5 John F. DiPersio,6 John V. Catalano,7 Michael W.N. Deininger,8* Carole B. Miller,9 Richard T. Silver,10 Moshe Talpaz,11 Elliott F. Winton,12 Jimmie H. Harvey, Jr.,13 Murat O. Arcasoy,14 Elizabeth O. Hexner,15 Roger M. Lyons,16Azra Raza,17 Kris Vaddi,4 William Sun,4 Wei Peng,4Victor Sandor,4 and Hagop Kantarjian,1 for the COMFORT-I investigators

1The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 2Mayo Clinic, Scottsdale, AZ, USA; 3Stanford Cancer Institute, Stanford, CA, USA; 4Incyte Corporation, Wilmington, DE, USA; 5Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada; 6Washington University School of Medicine, St. Louis, MO, USA; 7Frankston Hospital and Department of Clinical Haematology, MonashUniversity, Frankston, Australia; 8*Oregon Health and Science University, Portland, OR, USA; 9Saint Agnes Cancer Institute, Baltimore, MD, USA; 10Weill Cornell Medical Center, New York, NY, USA; 11University of Michigan, Ann Arbor, MI, USA; 12Emory University School of Medicine, Atlanta, GA, USA; 13Birmingham Hematology and Oncology, Birmingham, AL; 14Duke University Health System, Durham, NC, USA; 15Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA; 16Cancer Care Centers of South Texas/US Oncology, San Antonio, TX, USA; 17Columbia Presbyterian Medical Center, New York, NY, USA

*Currently at Division of Hematology and Hematologic Malignancies and Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA

comfort i
COMFORT-I

Background

  • Placebo-controlled, randomized, double-blind, phase III study
  • Primary analysis (median follow-up 32 weeks)1
    • Significant improvements in spleen volume, MF-related symptoms, and QoL measures with ruxolitinibcompared with placebo
  • Ruxolitinib treatment was associated with an overall survival advantage relative to placebo at a median follow-up of 51 weeks1
  • 2-Year analysis (median follow-up 102 wks):2
    • Durable spleen volume reductions and QoL improvements
    • Continued overall survival advantage despite placebo crossover

Objective

  • To report longer-term efficacy, overall survival, and safety of ruxolitinib in patients from the COMFORT-I study
  • Verstovsek S, et al. N Engl J Med. 2012; 366:799-807.
  • Verstovsek S, et al. Haematologica. 2013 Sept 13. Epub ahead of print. PMID 24038026.
durability of spleen volume reduction
Durability of Spleen Volume Reduction
  • In patients originally randomized to ruxolitinib, 59% achieved a ≥35% reduction in spleen volume

1.0

≥10% reduction (n=91)

0.8

≥35% reduction (n=91)

0.6

Probability

0.4

0.2

0

0

8

16

24

32

40

48

56

64

72

80

88

96

104

112

120

128

136

144

Weeks from initial ≥ 35% spleen volume reduction

Number of patients at risk

≥35% reduction

91

86

77

75

68

62

59

54

51

49

42

40

38

37

27

25

23

1

1

≥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.

improvements in eortc qlq c30 over time
Improvements in EORTC QLQ-C30 Over Time

Global Health Status/QoL

Fatigue

10

25

20

15

20

5

15

15

10

0

Mean Change From Baseline

Mean Change From Baseline

10

10

-5

Mean Change From Baseline

5

5

5

-10

0

0

12

24

36

48

60

72

84

96

108

120

132

144

0

12

24

36

48

60

72

84

96

108

120

132

144

-15

0

Weeks

Weeks

RUX

PBO

0

-5

Arrows indicate improvement

Physical Functioning

Role Functioning

-20

-10

-5

-25

-5

-15

-10

-30

-20

Weeks

Mean Change From Baseline

-10

-35

-25

-15

0

12

24

36

48

60

72

84

96

108

120

132

144

0

12

24

36

48

60

72

84

96

108

120

132

144

Weeks

overall survival
Overall Survival
  • Overall survival favored patients originally randomized to ruxolitinib compared with patients originally randomized to placebo

1.0

Randomized to Ruxolitinib

0.8

*

Randomized to Placebo  Ruxolitinib

0.6

Probability

HR=0.69 (95% CI: 0.46, 1.03); P=0.067

0.4

No. of deaths: Ruxolitinib=42; Placebo=54

Median follow-up: 149 weeks

0.2

Percent of at-risk placebo who crossed over or discontinued

4

13

22

35

54

73

88

97

99

100

100

100

100

100

100

100

100

100

100

100

100

100

0

Number of patients at risk

0

8

16

24

32

40

48

56

64

72

80

88

96

104

112

120

128

136

144

152

160

168

176

Ruxolitinib

155

155

153

148

145

143

137

131

125

124

122

115

112

111

111

108

106

101

84

45

19

1

0

Weeks

Placebo

154

153

149

144

134

129

119

114

107

105

100

100

95

92

88

85

82

79

68

38

28

8

0

30

*By week 80, all patients originally randomized to placebo discontinued or crossed over to ruxolitinib therapy

mean platelet count and hemoglobin level over time
Mean Platelet Count and Hemoglobin Level Over Time

Platelet Count

Hemoglobin

370

115

Ruxolitinib

Ruxolitinib

Placebo

Placebo

110

320

105

270

Mean Hemoglobin (g/L)

Mean Platelets (x109/L)

100

220

95

170

90

120

85

0

12

24

36

48

60

72

84

96

108

120

132

144

0

12

24

36

48

60

72

84

96

108

120

132

144

Weeks

Weeks

Number of patients

Number of patients

155

145

143

136

124

113

110

107

104

100

94

88

RUX

155

144

143

136

124

112

110

107

104

100

94

88

79

79

151

132

113

83

37

PBO

151

128

112

82

37

incidence of new onset grade 3 or 4 anemia and thrombocytopenia over time
Incidence of New Onset Grade 3 or 4 Anemia and Thrombocytopenia Over Time

Ruxolitinib Grade 3

Ruxolitinib Grade 4

Placebo* Grade 3

Placebo* Grade 4

Anemia

Thrombocytopenia

18.7

3.8

0.8

0

0

  • Consistent with observations at the 2-year follow-up, grade 3 or 4 anemia and thrombocytopenia typically only occurred early (≤6 months) in ruxolitinib treatment and decreased with long-term therapy

*All patients receiving placebo at the primary analysis crossed over or discontinued within 3 months of the primary analysis; therefore, data for patients receiving placebo is shown for up to 6 months only

comfort i 3 year conclusions
COMFORT-I 3-Year: Conclusions
  • Reductions in spleen volume and improvements in symptoms and QoL measures were sustained with longer-term therapy
    • Overall survival favored patients originally randomized to ruxolitinib compared with those originally randomized to placebo
      • Results from exploratory analyses suggest cross over leads to an underestimation of the true survival difference between ruxolitinib and placebo
    • The incidence of new onset grade 3 or 4 anemia and thrombocytopenia decreased with longer-term therapy
    • There was no change in the rate, distribution, or severity of nonhematologic adverse events in patients originally randomized to ruxolitinib with longer-term treatment
  • Collectively, these data reinforce the durable efficacy and longer-term safety of ruxolitinib in patients with myelofibrosis
slide34

Update on the Long-term Efficacy and Safety of Momelotinib, a JAK1 and JAK2 Inhibitor, for the Treatment of Myelofibrosis

A Pardanani,1 J Gotlib,2 V Gupta,3 AW Roberts,4 M Wadleigh,5 S Sirhan,6LM Bavisotto,7 J Kawashima,8 P Lee,8 M Kowalski,8 W Deng,8 D Niforos,8 A Tefferi1

1Mayo Clinic, Rochester, MN, USA; 2Stanford University, Stanford, CA, USA; 3Princess Margaret Cancer Centre, Toronto, ON, Canada; 4Royal Melbourne Hospital, Parkville, Australia; 5Dana-Farber Cancer Institute, Boston, MA, USA; 6Jewish General Hospital, Montreal, QC, Canada; 7Porta Clinica, Seattle, WA, USA; 8Gilead Sciences, Foster City, CA, USA

American Society of Hematology

December 7-10, 2013

New Orleans, LA

Oral No. 61758

anemia response
Anemia Response

Transfusion dependence at baseline is defined as ≥ 2 units of RBC transfusions in the 30 days prior to C1/D1 and/or identified as transfusion dependent in medical history

duration of anemia response
Duration of Anemia Response

1.0

 Censored

 Event

0.9

Number of events (%): 18 (30.5)

Number of censored (%): 41 (69.5)

Median (days) (95% CI): 1,042 (514, NE)

0.8

0.7

0.6

Probability

0.5

0.4

0.3

0.2

0.1

0

600

800

0

400

200

1000

Duration of anemia response (days)

symptoms response at 3 months
Symptoms Response at 3 Months

100

90

80

70

Percent

60

50

40

30

20

10

0

Abdominal

discomfort

Fatigue

Pruritus

Cough

Edema

Bone pain

Fever

Early satiety

Night sweats

Marked Improvement - defined as

≥ 50% improvement from baseline

Complete Resolution

conclusions
Conclusions
  • Momelotinib was well tolerated overall.
    • Grade 3/4 thrombocytopenia (29%), neutropenia (5%), and elevated lipase (4%).
    • Peripheral neuropathy in 38% with all occurrences less than Grade 2
      • 2 patients stopped treatment due to neuropathy
      • 17 patients had neuropathy at baseline
  • Treatment improved splenomegaly and disease-related symptoms along with decreasing transfusion needs.
phase 3 study design gs us 352 0101
Phase 3 Study Design (GS-US-352-0101)

Screening

(≤ 35 days)

Long-term

Follow-up

Open-label Phase

Double-blind Treatment Phase

Momelotinib + placebo

Momelotinib

Momelotinib QD

N=420

1:1 randomization

Ruxolitinib + placebo

Momelotinib

Week 24

Day 1

Within 5 days of randomization

Week 192

Year 4

Year 5

slide40

Preliminary Report Of The STIM2 Study:  A Multicenter Stop Imatinib Trial For Chronic Phase Chronic Myeloid Leukemia De Novo Patients On Imatinib

Francois-Xavier Mahon, Franck E. Nicolini, Marie-Pierre Noël,

Martine Escoffre, Aude Charbonnier, Delphine Rea, Viviane Dubruille, Bruno Varet, Laurence Legros, Agnès Guerci,

Gabriel Etienne, Francois Guilhot, Stéphanie Dulucq, Philippe Rousselot, and Joelle Guilhot

on behalf of the Intergroupe Français des Leucémies Myéloïdes Chroniques

slide41

INTRODUCTION

A pilot and STIM1 demonstrated that Imatinib could be safely discontinued in patients with a sustained DMR with undetectable BCR-ABL transcripts for at least 2 years 1,2.

- Results since confirmed by the Australian TWISTER study3 .

- In both studies, 50% of the patients were

previously treated with IFN leading to a non-

homogeneous cohort of patients.

1.Rousselot et al. Blood 2007;109:58–602. Mahon et al. Lancet oncology, 2010;11: 1029-1035 3. Ross et al. Blood, 2013; 122:515-22).

slide42

STIM2 study: A multicenter Stop Imatinib trial for CML de novo only treated with imatinib

  • Main inclusion criteria
  • CMR for at least 2 years under treatment with imatinib  
  • Molecular monitoring according to international recommendations
  • Main exclusion criteria
  • < 18 years old  
  • Interfering treatment (corticosteroids, immunosuppressors, chemotherapy, radiotherapy)

N=200

characteristics of patients n 127
Characteristics of patients N=127
  • Number of patients included between 04/2011-09/2013: 131*
  • From 23 different French centers
  • Mean age at diagnosis: 54 years
  • Mean age at the inclusion: 61 years
  • Gender distribution: 63 males, 64 females
  • Median duration of CMR before stopping :35 months (24-97)
  • Sokal Score Low, intermediate, High, unk : 55, 52, 15, 5
  • Median Follow up: 16 months (range 0-27)

* Four patients previously treated by IFN incorrectly included were excluded

slide44

STIM study design

Q- RT-PCR from peripheral blood every month in the first year and every 2 months thereafter

STOP

Start Imatinib

Sustained CMR

for ≥ 2 years

CMR

Molecular recurrence: positivity of BCR–ABL transcript in Q-RT-PCR confirmed by a second analysis point indicating the increase of one log in relation to the first analysis point, at two successive assessments, or loss of MMR at one point.

Five BCR–ABL analyses by Q- RT-PCR during these 2 years

Sixth datapoint checked in centralized laboratory

Mahon FX et al. The Lancet Oncology, 2010;11(11): 1029-1035.

slide45

STIM2 study: Preliminary results

Molecular relapse

N = 52

slide46

Fluctuation of BCR-ABL detection after discontinuation

STOP

UMRD: undetectable minimumal residual disease at least in MR4.5

With > 50 000 copies of ABL gene

slide47

STIM2 study : Preliminary results

undetectable transcript

N = 35

Follow-up*:

15.7 mos (0.9-26.7)

undetectabletranscript

N = 127

Fluctuation PCR, non relapsing

N = 40

Time to fluctuation*:

2.3 mos (0.9-7.5)

Molecular relapse

N = 52

Time to relapse*:

2.0 mos (0 -8.0)

* Median (range) from Imatinib discontinuation

slide48

SURVIVAL WITHOUT CML TREATMENT STIM2

Event = treatment re-challenge

slide49

Conclusions

  • Imatinib can be safely and prospectively discontinued in pts with DMR of at least 2 years duration in patients treatedwith imatinib.
  • Positive fluctuation PCR results do not lead to CML relapse or progression thereforecompleteeradication of residualleukemic stem cellsmay not benecessary.
  • Theseresultsconfirmed the findings of the earlierstudies (STIM1).
  • The investigators plan to perform statistical analysis in the 3 different groups of patients.
  • The study recommended proposing discontinuation only in a clinical trial with close molecular monitoring.
summary
Summary
  • Genomic studies this year provided insights into the mutational status of MDS patients and identified CALR mutations in a large percentage JAK2 wild-type MPD patients.
  • Clinical trials are currently investigating the benefit of adding an additional agent to the standard of care of azacitidine in MDS.
  • New agents are in development and being evaluated in clinical trials for MDS and MPD.
  • CML trials are investigating stopping TKI therapy after a sustained and deep molecular response.