ClinicalTrials.gov. A phase 2 study of CPI-0610 with and without ruxolitinib in patients with myelofibrosis. NCT02158858. Updated January 29, 2021. Accessed March 17, 2021. https://clinicaltrials.gov/ct2/show/NCT02158858
ClinicalTrials.gov. A phase 3 study of pacritinib in patients with primary myelofibrosis, post polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis (PACIFICA). NCT03165734. Updated March 10, 2021. Accessed March 17, 2021. https://clinicaltrials.gov/ct2/show/NCT03165734
ClinicalTrials.gov. A safety trial of fedratinib in subjects with DIPSS, intermediate or high-risk primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis and previously treated with ruxolitinib with concomitant luspatercept for subjects with anemia (FREEDOM). NCT03755518. Updated January 12, 2021. Accessed March 17, 2021. https://clinicaltrials.gov/ct2/show/NCT03755518
ClinicalTrials.gov. A study comparing imetelstat versus best available therapy for the treatment of intermediate-2 or high-risk myelofibrosis (MF) who have not responded to Janus kinase (JAK)-inhibitor treatment. NCT04576156. Updated February 21, 2021. Accessed March 17, 2021. https://clinicaltrials.gov/ct2/show/NCT04576156
ClinicalTrials.gov. A study of momelotinib versus danazol in symptomatic and anemic myelofibrosis patients (MOMENTUM). NCT04173494. Updated March 16, 2021. Accessed March 17, 2021. https://clinicaltrials.gov/ct2/show/NCT04173494
ClinicalTrials.gov. MPN-RC 118 AVID200 in myelofibrosis. NCT03895112. Updated June 2, 2020. Accessed March 17, 2021. https://clinicaltrials.gov/ct2/show/NCT03895112
ClinicalTrials.gov. To evaluate the efficacy and safety of parsaclisib and ruxolitinib in participants with myelofibrosis. NCT04551066. Updated March 3, 2021. Accessed March 17, 2021. https://clinicaltrials.gov/ct2/show/NCT04551066
Diaz AE, Mesa RA. Pacritinib and its use in the treatment of patients with myelofibrosis who have thrombocytopenia. Future Oncol. 2018;14:797-807.
Gerds AT, Savona MR, Scott SL, et al. Results of PAC203: a randomized phase 2 dose-finding study and determination of the recommended dose of pacritinib in patients with myelofibrosis. Blood. 2019;134: Abstract 667.
Harrison C, Andreasson B, Cambier N, et al. Long term safety of memelotinib in JAKi naïve and previously JAKi treated intermediate/high risk myelofibrosis patients. HemaSphere. 2020;4(S1): Abstract EP1113.
Harrison C, Garcia JS, Mesa R, et al. Navitoclax in combination with ruxolitinib in patients with primary or secondary myelofibrosis: a phase 2 study. HemaSphere. 2020;4(S1): Abstract EP1081.
Harrison CN, Schaap N, Mesa RA. Management of myelofibrosis after ruxolitinib failure. Ann Hematol. 2020;99:1177-1191.
Harrison CN, Schaap N, Vannucchi A, et al. Fedratinib induces spleen responses and reduces symptom burden in patients with myeloproliferative neoplasm (MPN)-associated myelofibrosis (MF) and low platelet counts, who were ruxolitinib-naïve or previously treated with ruxolitinib. Blood. 2019;134: Abstract 668.
Hillmen P, et al. Phase 1b-2 study of KRT-232, a first-in-class, oral, small molecule inhibitor of murine double minute 2 (MDM2), in combination with acalabrutinib for the treatment of relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) or R/R diffuse large b-cell lymphoma (DLBCL). Blood. 2020;136: Abstract 3024.
INREBIC® (fedratinib) [prescribing information]. Celgene Corporation. Approved 2019. Revised August 2019.
INREBIC® (fedratinib) Product Information. European Medicines Agency (EMA). Published March 3. 2021. Accessed March 17, 2021. https://www.ema.europa.eu/en/documents/product-information/inrebic-epar-product-information_en.pdf
Kiladjian JJ, Mascarenhas J, Komrokji R, et al. Imetelstat treatment results in clinical benefits, including improved overall survival, in patients with higher-risk triple-negative myelofibrosis relapsed/refractory to Janus kinase inhibitors (JAKi). Blood. 2020;136: Abstract 3084.
Mascarenhas J, Komrokji R, Cavo M, et al. Imetelstat is effective treatment for patients with intermediate-2 or high-risk myelofibrosis who have relapsed on or are refractory to Janus kinase inhibitor therapy: results of a phase 2 randomized study of two dose levels. Blood. 2018;132: Abstract 685.
Mascarenhas J, Komrokji R, Cavo M, et al. Telomerase activity, telomere length and hTERT expression correlate with clinical outcomes in higher-risk myelofibrosis (MF) relapsed/refractory (R/R) to Janus kinase inhibitor treated with imetelstat. Blood. 2020;136: Abstract 347.
Mascarenhas J, Komrokji R, Martino B, et al. Favorable overall survival with imetelstat treatment correlates with other clinical benefits in intermediate 2 or high risk myelofibrosis relapsed/refractory to Janus kinase inhibitor. HemaSphere. 2020;4(S1): Abstract EP1107.
Mascarenhas J, Komrokji RS, Cavo M, et al. Favorable overall survival with imetelstat treatment correlates with other clinical benefits in intermediate 2 or high risk myelofibrosis relapsed/refractory to Janus kinase inhibitor. Blood. 2020;136: Abstract 53.
McLornan DP, Harrison CN. Guidance on changing therapy choice in myelofibrosis. Blood Adv. 2020;4:607-610.
Pardanani A, Tefferi A. Definition and management of ruxolitinib treatment failure in myelofibrosis. Blood Cancer J. 2014;4:1-7.
Pemmaraju N, Garcia JS, Potluri J, et al. The addition of navitoclax to ruxolitinib demonstrates efficacy within different high-risk populations in patients with relapsed/refractory myelofibrosis. Blood. 2020;136: Abstract 52.
Pemmaraju N, Gupta V, Ali H, et al. A multicenter phase 1/2 clinical trial of tagraxofusp, a cd123-targeted therapy, in patients with poor-risk primary and secondary myelofibrosis. Blood. 2020;136: Abstract 2986.
Sørensen AL, Mikkelsen SU, Knudsen TA, et al. Ruxolitinib and interferon-α2 combination therapy for patients with polycythemia vera or myelofibrosis: a phase II study. Haematologica. 2020;105:2262-2272.
Tse C, Shoemaker AR, Adickes J, et al. ABT-263: A potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res. 2008;68:3421-3428.
Verstovsek S, Mascarenhas J, Kremyanskaya M, et al. CPI-0610, bromodomain and extraterminal domain protein (BET) inhibitor, as :add-on” to tuxolitinib, in advanced myelofibrosis pateitns with suboptimal response: Update of MANIFEST phase 2 study. Blood. 2020;136: Abstract 56.
Waibel M, et al. Combined targeting of JAK2 and Bcl-2/Bcl-xL to cure mutant JAK2-driven malignancies and overcome acquired resistance to JAK2 inhibitors. Cell Rep. 2013;5:1047-1105.
Yacoub A, Pettit K, Bradley TJ, et al. A phase 2 study of the LSD1 inhibitor IMG-7289 (bomedemstat) in patients with advanced myelofibrosis. Blood. 2020;136: Abstract 51
Yasuda S, Aoyama S, Yoshimoto R, et al. MPL overexpression induces a high level of mutant-calr/MPL complex: a novel mechanism of ruxolitinib resistance in myeloproliferative neoplasms with CALR mutations. Blood. 2020;136: Abstract 1262.

WebMD Global requires each individual who is in a position to control the content of one of its educational activities to disclose any relevant financial relationships occurring within the past 12 months that could create a conflict of interest.

Faculty

Claire Harrison, DM, FRCPath

Professor of Hematology and Clinical Director
Department of Hematology
Guy's and St. Thomas NHS Foundation Trust
London, United Kingdom

Disclosures

Disclosure: Claire Harrison, DM, FRCPath, has disclosed the following relevant financial relationships:
Served as an advisor or consultant for: AbbVie; AOP; Bristol Myers Squibb Company; Celgene; Constellation; CTI Bio; Novartis; Promedior; Roche
Served as a speaker or a member of a speakers bureau for: AbbVie; AOP; Constellation; Janssen; Novartis; Roche
Received grants for clinical research from: Celgene; Constellation; Novartis

John Mascarenhas, MD

Associate Professor of Medicine
Tisch Cancer Institute
Icahn School of Medicine at Mount Sinai
New York, New York, United States

Disclosures

Disclosure: John Mascarenhas, MD, has disclosed the following relevant financial relationships:
Served as an advisor or consultant for: Bristol Myers Squibb Company; Celgene; Constellation; Geron; Incyte; Kartos; PharmaEssentia; Roche
Received grants for clinical research from: CTI Bio; Forbius; Incyte; Janssen; Kartos; Merck; Novartis; PharmaEssentia; Roche

Editors

Sanneke Koekkoek

Medical Education Director, WebMD Global, LLC

Disclosures

Disclosure: Sanneke Koekkoek, has disclosed no relevant financial relationships.

Jason Luis Quinones, PhD

Scientific Content Manager, Medscape, LLC

Disclosures

Disclosure: Jason Luis Quinones, PhD, has disclosed no relevant financial relationships.

Content Reviewer

Robert Morris, PharmD

Associate Director, Accreditation and Compliance, Medscape, LLC

Disclosures

Disclosure: Robert Morris, PharmD, has disclosed the following relevant financial relationships:
Served as an advisor or consultant for: ViiV Healthcare
Owns stock, stock options, or bonds from: GlaxoSmithKline

Medscape, LLC staff have disclosed that they have no relevant financial relationships.

Peer Reviewer

This activity has been peer reviewed and the reviewer has disclosed no relevant financial relationships.

CPD

New Targets for Old Challenges in Myelofibrosis

Authors: Claire Harrison, DM, FRCPath; John Mascarenhas, MD
CPD Released: 3/25/2021
THIS ACTIVITY HAS EXPIRED
Valid for credit through: 3/25/2022

Start Activity

Target Audience and Goal Statement

This educational activity is intended for an international audience of non-US hematology/oncology specialists and pathologists.

The goal of this activity is to raise physician awareness of recent developments in treating patients with ruxolitinib-failed myelofibrosis.

Upon completion of this activity, participants will:

Have increased knowledge regarding the
- Incidence of ruxolitinib-resistance/intolerance in patients with myelofibrosis
- Clinical data with novel approaches to ruxolitinib-resistant myelofibrosis
Demonstrate greater confidence in their ability to
- Describe novel targets in treating patients with myelofibrosis

Disclosures

Faculty

Claire Harrison, DM, FRCPath

Professor of Hematology and Clinical Director
Department of Hematology
Guy's and St. Thomas NHS Foundation Trust
London, United Kingdom

Disclosures

Disclosure: Claire Harrison, DM, FRCPath, has disclosed the following relevant financial relationships:
Served as an advisor or consultant for: AbbVie; AOP; Bristol Myers Squibb Company; Celgene; Constellation; CTI Bio; Novartis; Promedior; Roche
Served as a speaker or a member of a speakers bureau for: AbbVie; AOP; Constellation; Janssen; Novartis; Roche
Received grants for clinical research from: Celgene; Constellation; Novartis

John Mascarenhas, MD

Associate Professor of Medicine
Tisch Cancer Institute
Icahn School of Medicine at Mount Sinai
New York, New York, United States

Disclosures

Disclosure: John Mascarenhas, MD, has disclosed the following relevant financial relationships:
Served as an advisor or consultant for: Bristol Myers Squibb Company; Celgene; Constellation; Geron; Incyte; Kartos; PharmaEssentia; Roche
Received grants for clinical research from: CTI Bio; Forbius; Incyte; Janssen; Kartos; Merck; Novartis; PharmaEssentia; Roche

Editors

Sanneke Koekkoek

Medical Education Director, WebMD Global, LLC

Disclosures

Disclosure: Sanneke Koekkoek, has disclosed no relevant financial relationships.

Jason Luis Quinones, PhD

Scientific Content Manager, Medscape, LLC

Disclosures

Disclosure: Jason Luis Quinones, PhD, has disclosed no relevant financial relationships.

Content Reviewer

Robert Morris, PharmD

Associate Director, Accreditation and Compliance, Medscape, LLC

Disclosures

Disclosure: Robert Morris, PharmD, has disclosed the following relevant financial relationships:
Served as an advisor or consultant for: ViiV Healthcare
Owns stock, stock options, or bonds from: GlaxoSmithKline

Medscape, LLC staff have disclosed that they have no relevant financial relationships.

Peer Reviewer

This activity has been peer reviewed and the reviewer has disclosed no relevant financial relationships.

Accreditation Statements

For Physicians

The Faculty of Pharmaceutical Medicine of the Royal Colleges of Physicians of the United Kingdom (FPM) has reviewed and approved the content of this educational activity and allocated it 0.25 continuing professional development credits (CPD).

Contact WebMD Global

For questions regarding the content of this activity, contact the accredited provider for this CME/CE activity noted above. For technical assistance, contact [email protected]

Instructions for Participation and Credit

There are no fees for participating in or receiving credit for this online educational activity. For information about your eligibility to claim credit, please consult your professional licensing board.

This activity is designed to be completed within the time designated on the title page; physicians should claim only those credits that reflect the time actually spent participating in the activity. To successfully earn credit, participants must complete the activity online during the credit eligibility period that is noted on the title page.

Follow these steps to claim a credit certificate for completing this activity:

Read the information provided on the title page regarding the target audience, learning objectives, and author disclosures, read and study the activity content and then complete the post-test questions. If you earn a passing score on the post-test and we have determined based on your registration profile that you may be eligible to claim CPD credit for completing this activity, we will issue you a CPD credit certificate.
Once your CPD credit certificate has been issued, you may view and print the certificate from your CME/CE Tracker. CPD credits will be tallied in your CME/CE Tracker and archived for 6 years; at any point within this time period you can print out the tally as well as the certificates by accessing "Edit Your Profile" at the top of the Medscape Education homepage.

We encourage you to complete an Activity Evaluation to provide feedback for future programming.

You may now view or print the certificate from your CME/CE Tracker. You may print the certificate but you cannot alter it. Credits will be tallied in your CME/CE Tracker and archived for 6 years; at any point within this time period you can print out the tally as well as the certificates by accessing "Edit Your Profile" at the top of your Medscape homepage.

*The credit that you receive is based on your user profile.

From Medscape Education

CPD

New Targets for Old Challenges in Myelofibrosis

Authors: Claire Harrison, DM, FRCPath; John Mascarenhas, MDFaculty and Disclosures

THIS ACTIVITY HAS EXPIRED

CPD Released: 3/25/2021

Valid for credit through: 3/25/2022

processing....

AE = adverse event
ASH = American Society of Hematology
BCL-2 = B-cell lymphoma 2
BCL-XL = B-cell lymphoma extra large
BET = bromodomain and extraterminal domain protein
BMF = bone marrow fibrosis
BPDCN = blastic plasmacytoid dendritic cell neoplasm
CALR = calreticulin gene
CML = chronic myelogenous leukemia
CT = computed tomography
EOC6 = end of cycle 6
GI = gastrointestinal
Hgb = hemoglobin
HU = hydroxyurea
IRC = independent review committee
IV = intravenous
IWG-MRT = International Working Group – Myeloproliferative Neoplasms Research and Treatment
LSD1 = lysine-specific demethylase 1
MF = myelofibrosis
MPL = thrombopoietin receptor gene
MPN = myeloproliferative neoplasm
MPN-SAF = Myeloproliferative Neoplasm Symptom Assessment Form
MRI = magnetic resonance imaging
OS = overall survival
PD = pharmacodynamics
PFS = progression-free survival
QoL = quality of life
R/R = relapsed/refractory
SAE = serious adverse event
SVR = spleen volume reduction
TD = transfusion dependence
TEAE = treatment-emergent adverse event
TGFβ = transforming growth factor beta
TI = transfusion independence
TKI = tyrosine kinase inhibitor
TN = triple negative
TSS = total symptom score
VAF = variant allele frequency
WBC = white blood cell

« Return to: New Targets for Old Challenges in Myelofibrosis

CPD Information Download Slides

Activity Transcript

Print
Like Tweet

References

Faculty and Disclosures

Faculty

Claire Harrison, DM, FRCPath

John Mascarenhas, MD

Editors

Sanneke Koekkoek

Jason Luis Quinones, PhD

Content Reviewer

Robert Morris, PharmD

Peer Reviewer

CPD

New Targets for Old Challenges in Myelofibrosis

Target Audience and Goal Statement

Disclosures

Faculty

Claire Harrison, DM, FRCPath

John Mascarenhas, MD

Editors

Sanneke Koekkoek

Jason Luis Quinones, PhD

Content Reviewer

Robert Morris, PharmD

Peer Reviewer

Accreditation Statements

For Physicians

Instructions for Participation and Credit

New Targets for Old Challenges in Myelofibrosis