HEMATOLOGIC MALIGNANCIES: Edited by Miguel A. Sanz and María-Victoria MateosNovel therapeutic agents for myelofibrosis after failure or suboptimal response to JAK2 inhbitorsBreccia, Massimo; Assanto, Giovanni Manfredi; Laganà, Alessandro; Scalzulli, Emilia; Martelli, Maurizio Author Information Department of Translational and Precision Medicine, Sapienza University, Rome, Italy Correspondence to Massimo Breccia, MD, Hematology, Department of Translational and Precision Medicine, Sapienza University, Via Benevento 6, 00161 Rome, Italy. Tel: +3906857951; fax: +390644241984; e-mail: [email protected] Current Opinion in Oncology 34(6):p 729-737, November 2022. | DOI: 10.1097/CCO.0000000000000898 Buy Metrics Abstract Purpose of review JAK2 inhibitors have changed the therapeutic strategies for the management of primary and secondary myelofibrosis. Ruxolitinib, the first available agent, improved disease-related symptoms, spleen volume, and overall survival compared to conventional chemotherapy. It has been revealed that after 3 years of treatment, about 50% of patients discontinued ruxolitinib for resistance and/or intolerance and should be candidate to a second line of treatment. Recent findings Second-generation tyrosine kinase inhibitors have been tested in this setting, but all these new drugs do not significantly impact on disease progression. Novel agents are in developments that target on different pathways, alone or in combination with JAK2 inhibitors. Summary In this review, we summarize all the clinical efficacy and safety data of these drugs providing a vision of the possible future. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.