Current hematologic malignancy reports · 2026
Molecular Response, Event-Free Survival, and Treatment-Free Remission in Myeloproliferative Neoplasms: Update and Review with Insights from MPN Asia 2026.
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Abu-Zeinah Ghaith, Hobbs Gabriela S, Rampal Raajit K, Lee Sung-Eun, Gill Harinder, Komrokji Rami, Tashi Tsewang, Bose Prithviraj, Mascarenhas John, Yacoub Abdulraheem, Oh Stephen T, Shimoda Kazuya, Reeves Brandi N, Duan Minghui, Yu Lennex Hsueh-Lin, Qin Albert, Prchal Josef T, Kaushansky Kenneth, Mesa Ruben A
Аннотация
PURPOSE OF REVIEW: Therapeutic goals in BCR::ABL1-negative myeloproliferative neoplasms (MPNs) are evolving to include biologically anchored measures of disease modification with control of blood counts, splenomegaly, and symptoms. Disease modification endpoints and their linkage to survival in MPNs were central to the framework of MPN Asia 2026, which took place in Seoul. This review summarizes key themes from MPN Asia 2026 and relevant recent literature, examining the evolving roles of molecular response and long-term clinical benefits within a broader disease-modification framework across polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF).
RECENT FINDINGS: Clinical trials with ropeginterferon alfa-2b were central to the discussions given these studies have contributed to the evolving paradigm of disease modification in MPNs, underscoring the importance of molecular response and event-free survival (EFS) in MPN management. In PV, ropeginterferon alfa-2b treatment provides a clinical model linking durable hematologic control and deep JAK2V617F variant allele frequency (VAF) reduction with improved long-term outcomes such as EFS, and prospective treatment-discontinuation strategies. Data from Europe and Asia supports the importance of early disease control, adequate interferon exposure, and longitudinal molecular monitoring. In ET, randomized data with ropeginterferon alfa-2b and emerging new treatment approaches such as lysine-specific demethylase 1 inhibition and mutant CALR-directed therapy are incorporating molecular endpoints into clinical development. However, the association between VAF reduction and thrombosis prevention, disease modification, EFS, and treatment-free remission (TFR) need to be elucidated. In MF, molecular profiling is already integral to prognostication and treatment selection, and disease modification assessment will likely require endpoints encompassing more than symptoms and spleen response, such as anemia response, bone marrow fibrosis change, clonal evolution, patient-reported outcomes, and importantly progression-free and overall survival. Molecular response, clonal suppression, prevention of vascular and progression events, survival outcomes such as EFS and TFR play increasingly important roles in MPN management.
RECENT FINDINGS: Clinical trials with ropeginterferon alfa-2b were central to the discussions given these studies have contributed to the evolving paradigm of disease modification in MPNs, underscoring the importance of molecular response and event-free survival (EFS) in MPN management. In PV, ropeginterferon alfa-2b treatment provides a clinical model linking durable hematologic control and deep JAK2V617F variant allele frequency (VAF) reduction with improved long-term outcomes such as EFS, and prospective treatment-discontinuation strategies. Data from Europe and Asia supports the importance of early disease control, adequate interferon exposure, and longitudinal molecular monitoring. In ET, randomized data with ropeginterferon alfa-2b and emerging new treatment approaches such as lysine-specific demethylase 1 inhibition and mutant CALR-directed therapy are incorporating molecular endpoints into clinical development. However, the association between VAF reduction and thrombosis prevention, disease modification, EFS, and treatment-free remission (TFR) need to be elucidated. In MF, molecular profiling is already integral to prognostication and treatment selection, and disease modification assessment will likely require endpoints encompassing more than symptoms and spleen response, such as anemia response, bone marrow fibrosis change, clonal evolution, patient-reported outcomes, and importantly progression-free and overall survival. Molecular response, clonal suppression, prevention of vascular and progression events, survival outcomes such as EFS and TFR play increasingly important roles in MPN management.