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    Faculty & Disclosures
    Prof. John Mascarenhas

    Icahn School of Medicine at Mount Sinai
    New York, NY, USA

    John Mascarenhas is a professor of medicine at the Icahn School of Medicine at Mount Sinai (ISMMS) in New York, NY, USA, a member of the Tisch Cancer Institute, the director of the Adult Leukemia Program and leader of clinical research within the Myeloproliferative Disorders Research Program at ISMMS. read more

    As a clinical investigator in malignant haematology with a focus on translational research in myeloproliferative neoplasms (MPN), Prof. Mascarenhas is primarily responsible for the clinical trials portion of the Myeloproliferative Disorders Research Program at ISMMS. Prof. Mascarenhas is also the principal investigator (PI) of the clinical trials project within the National Cancer Institute sponsored by the Myeloproliferative Neoplasm Research Consortium. He has served as a PI or study chair of multiple investigator-initiated and industry-sponsored early- and late-phase clinical trials evaluating innovative approaches to the treatment of MPN and secondary leukaemia.

    Prof. John Mascarenhas discloses Advisory board or panel fees from AbbVie, Bristol Myers Squibb, Celgene, CTI BioPharma, Galecto Biotech, Geron Corporation, GlaxoSmithKline, Imago BioSciences, Inc., Incyte Corporation, Kartos Therapeutics, Karyopharm Therapeutics, MorphoSys, Novartis, Pfizer, PharmaEssentia and Sierra Oncology. Grants/research support from AbbVie, Bristol Myers Squibb, Geron Corporation, Incyte Corporation, Kartos Therapeutics, Novartis and PharmaEssentia.
    Dr Raajit Rampal

    Memorial Sloan Kettering Cancer Center
    New York, NY, USA

    Raajit Rampal is a haematologic oncologist and associate member at the Memorial Sloan Kettering Cancer Center, and clinical director of the leukaemia service, based in New York, NY, USA. read more

    Dr Rampal is a physician-scientist with an active laboratory, and leads the clinical myeloproliferative neoplasms (MPN) programme at the Memorial Sloan Kettering Cancer Center. He received his MD and PhD at Stony Brook University, New York and completed his haematology/oncology fellowship at the Memorial Sloan Kettering Cancer Center, with post-doctoral training in the lab of Ross Levine. The focus of Dr Rampal’s research has been to utilize genetic insights from primary patient samples to elucidate mechanisms of pathogenesis in acute myeloid leukaemia and the Philadelphia chromosome-negative MPN, and to develop novel therapeutic strategies for these diseases.

    Dr Raajit Rampal discloses Advisory board or panel fees from AbbVie, Galecto Biotech, GlaxoSmithKline, Incyte Corporation, Kartos Therapeutics, Karyopharm Therapeutics, PharmaEssentia and SDP Pharma. Consultancy fees from Bristol Myers Squibb/Celgene, CTI BioPharma, MorphoSys, Servier, Stemline Therapeutics Inc. and Zentalis Pharmaceuticals. Grants/research support from Constellation Pharmaceuticals, Ryvu Therapeutics, Stemline Therapeutics Inc. and Zentalis Pharmaceuticals.
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    What are key considerations when selecting a JAK inhibitor for first-line therapy in myelofibrosis?
    What side effects are associated with JAK inhibitors in myelofibrosis and how can they be managed?
    What are the options following treatment failure with a first-line JAK inhibitor in myelofibrosis?
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    Haematological Malignancies, Rare Diseases CE/CME accredited

    touchIN CONVERSATION
    A relaxed discussion between two faculty focussed on real world clinical issues. Useful tips below will show how to navigate the activity. Join the conversation. Close

    Optimizing outcomes of JAK inhibition in myelofibrosis: Practical considerations for the clinic

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    • Downloads including slides are available for this activity in the Toolkit
    Learning Objectives

    After watching this activity, participants should be better able to:

    • Discuss considerations for selecting an appropriate JAK inhibitor in the first-line treatment of myelofibrosis
    • Plan strategies for managing side effects associated with JAK inhibition in patients with myelofibrosis
    • Evaluate management approaches following lack of treatment success with first-line JAK inhibitor treatment in patients with myelofibrosis
    Overview

    In this activity, two expert haematologic oncologists respond to questions from the haematology and oncology communities on how to select a first-line JAK inhibitor for patients with myelofibrosis, the key side effects associated with JAK inhibitors and how these are best managed, and review second-line treatment options following first-line JAK inhibitor treatment failure.

    This activity is jointly provided by USF Health and touchIME. read more

    Target Audience

    Haematologists and oncologists (including haematologic oncologists) involved in the management of myelofibrosis.

    Disclosures

    USF Health adheres to the Standards for Integrity and Independence in Accredited Continuing Education. All individuals in a position to influence content have disclosed to USF Health any financial relationship with an ineligible organization. USF Health has reviewed and mitigated all relevant financial relationships related to the content of the activity. The relevant relationships are listed below. All individuals not listed have no relevant financial relationships.

    Faculty

    Prof. John Mascarenhas discloses Advisory board or panel fees from AbbVie, Bristol Myers Squibb, Celgene, CTI BioPharma, Galecto Biotech, Geron Corporation, GlaxoSmithKline, Imago BioSciences, Inc., Incyte Corporation, Kartos Therapeutics, Karyopharm Therapeutics, MorphoSys, Novartis, Pfizer, PharmaEssentia and Sierra Oncology. Grants/research support from AbbVie, Bristol Myers Squibb, Geron Corporation, Incyte Corporation, Kartos Therapeutics, Novartis and PharmaEssentia.

    Dr Raajit Rampal discloses Advisory board or panel fees from AbbVie, Galecto Biotech, GlaxoSmithKline, Incyte Corporation, Kartos Therapeutics, Karyopharm Therapeutics, PharmaEssentia and SDP Pharma. Consultancy fees from Bristol Myers Squibb/Celgene, CTI BioPharma, MorphoSys, Servier, Stemline Therapeutics Inc. and Zentalis Pharmaceuticals. Grants/research support from Constellation Pharmaceuticals, Ryvu Therapeutics, Stemline Therapeutics Inc. and Zentalis Pharmaceuticals.

    Content Reviewer

    Amy Patterson, APRN: Speakers Bureau: Gilead/Kite (Relationships Terminated).

    Touch Medical Contributors

    Katrina Lester and Aniket Parikh have no financial interests/relationships or affiliations in relation to this activity.

    USF Health Office of Continuing Professional Development and touchIME staff have no financial interests/relationships or affiliations in relation to this activity.

    Requirements for Successful Completion

    In order to receive credit for this activity, participants must review the content and complete the post-test and evaluation form. Statements of credit are awarded upon successful completion of the post-test and evaluation form.

    If you have questions regarding credit please contact cpdsupport@usf.edu.

    Accreditations

    Physicians

    This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through a joint providership of USF Health and touchIME. USF Health is accredited by the ACCME to provide continuing medical education for physicians.

    USF Health designates this enduring material for a maximum of 0.75 AMA PRA Category 1 CreditTM.  Physicians should claim only the credit commensurate with the extent of their participation in the activity.

    The European Union of Medical Specialists (UEMS) – European Accreditation Council for Continuing Medical Education (EACCME) has an agreement of mutual recognition of continuing medical education (CME) credit with the American Medical Association (AMA). European physicians interested in converting AMA PRA Category 1 CreditTM into European CME credit (ECMEC) should contact the UEMS (www.uems.eu).

    Advanced Practice Providers

    Physician Assistants may claim a maximum of 0.75 Category 1 credits for completing this activity. NCCPA accepts AMA PRA Category 1 CreditTM from organizations accredited by ACCME or a recognized state medical society.

    The AANPCP accepts certificates of participation for educational activities approved for AMA PRA Category 1 CreditTM by ACCME-accredited providers. APRNs who participate will receive a certificate of completion commensurate with the extent of their participation.

    LIVE Broadcast: 14 July 2023. Date of original release: 31 July 2023. Date credits expire: 31 July 2024.

    If you have any questions regarding credit please contact cpdsupport@usf.edu.

    This activity is CE/CME accredited

    To obtain the CE/CME credit(s) from this activity, please complete this post-activity test.

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    Topics covered in this activity

    Haematological Malignancies / Rare Diseases
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    This Activity Is Funded By:

    An independent medical education grant from Bristol Myers Squibb.
    This activity is jointly provided by USF Health and touchIME.

    The information provided by this CME activity is for continuing education purposes only and is not meant to substitute for the independent medical/clinical judgment of a healthcare provider relative to diagnostic and treatment options of a specific patient’s medical condition.

    USF is an Equal Opportunity / Affirmative Action / Equal Access Institution.

    USF Health is accredited by the Accreditation Council for Continuing Medical Education, the American Nurses Credentialing Center and the Accreditation Council for Pharmacy Education to provide continuing education to healthcare professionals. As an accredited provider, USF Health is required to disclose personal information to relevant accredited bodies that certify CME to process credits/contact hours, comply with reporting requirements, and for internal recordkeeping and regulatory purposes. USF Health does not share or sell any individual’s contact information or unique identifiers to any commercial supporter, advertiser, or third party without the specific permission of the individual.

    Unapproved products or unapproved uses of approved products may be discussed by the faculty; these situations may reflect the approval status in one or more jurisdictions. The presenting faculty have been advised by touchIME and USF Health to ensure that they disclose any such references made to unlabelled or unapproved use. No endorsement by touchIME or USF Health of any unapproved products or unapproved uses is either made or implied by mention of these products or uses in touchIME or USF Health activities. touchIME and USF Health accept no responsibility for errors or omissions.

    This content is intended for healthcare professionals.

    LIVE Broadcast: 14 July 2023.

    Date of original release: 31 July 2023. Date credits expire: 31 July 2024.

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    touchIN CONVERSATION
    Optimizing outcomes of JAK inhibition in myelofibrosis: Practical considerations for the clinic
    0.75 CE/CME credit
    Question 1/5
    Which of the following are the main targets of the JAK inhibitor, fedratinib?

    FLT3, FMS-like tyrosine kinase 3; JAK, Janus kinase.

    Fedratinib was designed as a potent JAK2-selective inhibitor, which also exhibits off-target inhibition of wild-type and mutant FLT3. Unlike ruxolitinib, which is a dual JAK1/JAK2 inhibitor, fedratinib is a weak JAK1 inhibitor. Specificity of fedratinib for JAK2 as opposed to JAK1 may reduce the incidence of infectious events due to less immunosuppression.

    Abbreviations

    FLT3, FMS-like tyrosine kinase 3; JAK, Janus kinase.

    Reference

    Talpaz M, Kiladjian JJ. Leukemia. 2021;35:1–17.

    Question 2/5
    Your 68-year-old male patient presenting with palpable splenomegaly was recently diagnosed with high-risk myelofibrosis. Diagnostic blood test results show a white blood cell count 21.2 x 109/L, haemoglobin levels 10.7 g/dL, platelet count 115 x 109/L and otherwise normal hepatic function and serum creatinine levels. Based on the 2022 NCCN guidelines, which of the following JAK inhibitors would you suggest prescribing first-line to best manage this patient?

    JAK, Janus kinase; NCCN, National Comprehensive Cancer Network.

    Fedratinib and ruxolitinib are FDA-approved JAK inhibitors for adults with intermediate-2 or high-risk myelofibrosis, ineligible for allogeneic HSCT, and have a platelet count ≥50 x 109/L. Pacritinib is FDA-approved for adults with intermediate or high-risk myelofibrosis with a platelet count <50 x 109/L who are ineligible for allogeneic HSCT.

    Abbreviations

    FDA, US Food Drug and Administration; HSCT, haematopoietic stem cell transplantation; JAK, Janus kinase.

    Reference

    Gerds AT, et al. J Natl Compr Canc Netw. 2022;20:1033–62.

    Question 3/5
    Your 69-year-old male patient with a platelet count 68 x 109/L was diagnosed with intermediate-2 myelofibrosis and subsequently treated with ruxolitinib. After 5 months at the maximum tolerated dose, he developed new palpable splenomegaly 6 cm below the left costal margin, indicating progressive disease. After discussions with your patient, you decide to switch to fedratinib. What do you do next?

    Fedratinib has an FDA black box warning for encephalopathy, including Wernike’s encephalopathy, due to thiamine (vitamin B1) deficiency.1,2 As such, patients’ thiamine levels, complete blood count with platelets, and nutritional status should be assessed prior to initiating fedratinib, periodically during treatment, and as clinically indicated.1,2 Fedratinib should not be initiated in patients with thiamine deficiency; thiamine levels should be restored prior to starting treatment.1,2

    Abbreviation

    FDA, US Food Drug and Administration.

    References

    1. FDA. Fedratinib PI. Available at: https://bit.ly/3NDVDtt (accessed 21 June 2023).
    2. Gerds AT, et al. J Natl Compr Canc Netw. 2022;20:1033–62.
    Question 4/5
    Your 75-year-old male patient with symptomatic high-risk myelofibrosis is ineligible for haematopoietic stem cell transplantation. Together, you discuss initiating treatment with a JAK inhibitor and review potential treatment-emergent side effects. How do you counsel your patient on common management strategies for haematological side effects associated with JAK inhibitor treatment?

    JAK, Janus kinase.

    In patients with myelofibrosis receiving JAK inhibitor therapy, haematological side effects, including anaemia and thrombocytopenia, commonly occur.1–6 These events can typically be managed with transfusional support and JAK inhibitor dose modifications;1,2,4,5,7 discontinuation of JAK inhibitor treatment may be required in a minority of patients.1–6

    Abbreviation

    JAK, Janus kinase.

    References

    1. Verstovsek S, et al. N Engl J Med. 2012;366:799–807.
    2. Harrison C, et al. N Engl J Med. 2012;366:787–98.
    3. Pardanani A, et al. JAMA Oncol. 2015:1:643–51.
    4. Harrison CN, et al. Lancet Haematol. 2017;4:e317–24.
    5. Mesa RA, et al. Lancet Haematol. 2017;4:e225–36.
    6. Mascarenhas J, et al. JAMA Oncol. 2018;4:652–9.
    7. Gerds AT, et al. J Natl Compr Canc Netw. 2022;20:1033–62.
    Question 5/5
    Despite an initial spleen response, 6 months after receiving first-line ruxolitinib at the maximum tolerated dose, your patient with high-risk myelofibrosis has a 29% increase in spleen volume vs their baseline measurement. Based on the 2022 NCCN guidelines, which of the following options would you consider for your patient, given they are not showing signs of anaemia or thrombocytopenia?

    HSCT, haematopoietic stem cell transplant; NCCN, National Comprehensive Cancer Network.

    NCCN guidelines advise that first-line ruxolitinib should be discontinued if there is no spleen response or improvement of symptoms after 6 months of treatment.1 Switching to fedratinib or clinical trial enrolment are NCCN recommendations following ruxolitinib failure in patients with higher-risk myelofibrosis and platelet count ≥50 x 109/L who are not transplant candidates.1 According to the NCCN guidelines, pacritinib can also be considered second line for patients with platelet counts ≥50 x 109/L with one prior JAK inhibitor,1 yet pacritinib is only FDA-approved for patients with intermediate or high-risk myelofibrosis with a platelet count <50 x 109/L.2

    Abbreviations

    FDA, US Food Drug and Administration; JAK, Janus kinase; NCCN, National Comprehensive Cancer Network.

    References

    1. Gerds AT, et al. J Natl Compr Canc Netw. 2022;20:1033–62.
    2. FDA. Pacritinib PI. Available at: https://bit.ly/3CBcVBl (accessed 20 June 2023).
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    This Activity Is Funded By:

    An independent medical education grant from Bristol Myers Squibb.
    This activity is jointly provided by USF Health and touchIME.

    The information provided by this CME activity is for continuing education purposes only and is not meant to substitute for the independent medical/clinical judgment of a healthcare provider relative to diagnostic and treatment options of a specific patient’s medical condition.

    USF is an Equal Opportunity / Affirmative Action / Equal Access Institution.

    USF Health is accredited by the Accreditation Council for Continuing Medical Education, the American Nurses Credentialing Center and the Accreditation Council for Pharmacy Education to provide continuing education to healthcare professionals. As an accredited provider, USF Health is required to disclose personal information to relevant accredited bodies that certify CME to process credits/contact hours, comply with reporting requirements, and for internal recordkeeping and regulatory purposes. USF Health does not share or sell any individual’s contact information or unique identifiers to any commercial supporter, advertiser, or third party without the specific permission of the individual.

    Unapproved products or unapproved uses of approved products may be discussed by the faculty; these situations may reflect the approval status in one or more jurisdictions. The presenting faculty have been advised by touchIME and USF Health to ensure that they disclose any such references made to unlabelled or unapproved use. No endorsement by touchIME or USF Health of any unapproved products or unapproved uses is either made or implied by mention of these products or uses in touchIME or USF Health activities. touchIME and USF Health accept no responsibility for errors or omissions.

    This content is intended for healthcare professionals.

    LIVE Broadcast: 14 July 2023.

    Date of original release: 31 July 2023. Date credits expire: 31 July 2024.

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