As If Myeloproliferative Neoplasms Weren't Already Challenging Enough

While the tools of precision medicine have led to transformative progress in myeloproliferative neoplasms (MPNs), these diseases remain at an inflection point, challenged by how to best harness molecular data for optimal patient care. This session will use a case-based approach to highlight how advances in the genetics of MPNs are being assimilated into prognostication and therapeutic decision-making. Clinical perspectives will be provided on managing resistance/intolerance to JAK inhibition and progression to accelerated/blast phase disease, which remain unmet needs in myelofibrosis. Lastly, speakers will discuss challenges related to the diagnosis and treatment of advanced systemic mastocytosis and focus on the new paradigm of KIT inhibition in these neoplasms.

Dr. Ann Mullally will discuss the molecular genetics of MPNs, encompassing both phenotypic driver mutations (JAK2, CALR, MPL) and concomitant high-risk mutations such as ASXL1. She will describe the biology of these mutations and their implications for both prognosis and treatment. Dr. Mullally will also review risk stratification in MPNs more broadly, focusing on recently published models which integrate clinical and molecular variables.

Dr. Ruben Mesa will discuss management of advanced phase MPNs. He will review what constitutes progression, including transformation to acute leukemia. Dr. Mesa will summarize the challenges related to defining resistance and/or intolerance to JAK inhibitors (e.g., ruxolitinib), and management strategies for these patients. Treatment options for accelerated and blast phase disease will be outlined, including both those with and those without a transplant option.

Dr. Jason Gotlib will highlight the challenges related to diagnosis and classification of advanced variants of systemic mastocytosis (advSM). He will review the treatment landscape of KIT inhibition in advSM, including selective KIT D816V inhibitors in clinical trials. Dr. Gotlib will summarize clinical and molecular markers for monitoring response and progression, and will outline a roadmap for addressing the unmet needs of advSM patients.