Dr Bewersdorf on Ruxolitinib Plus Abemaciclib in Myelofibrosis

Jan Bewersdorf, MD, hematology/oncology fellow, Memorial Sloan Kettering Cancer Center, discusses the design of an ongoing phase 1 (NCT05714072) investigating ruxolitinib (Jakafi) plus abemaciclib (Verzenio) in patients with primary or secondary myelofibrosis.

This multicenter, dose-escalation trial aims to determine whether the addition of the CDK4/6 inhibitor abemaciclib to the JAK inhibitor ruxolitinib improves ruxolitinib efficacy in patients with myelofibrosis. This trial is enrolling patients with primary or post–polycythemia vera or essential thrombocythemia myelofibrosis who have received ruxolitinib for at least 12 weeks and received a stable dose of either 10 mg or 15 mg of the agent twice daily for at least 4 weeks prior to the initiation of the study treatment. Patients are eligible for enrollment if they have an inadequate response to this ruxolitinib regimen, defined as palpable splenomegaly of at least 5 cm and/or active myeloproliferative neoplasm symptoms. The primary end points of this trial are safety, defining the maximum tolerated dose, and defining the recommended phase 2 dose. Secondary end points include overall response rate, progression-free survival, overall survival, and duration of response.

Patients in this trial will receive abemaciclib as an add-on to their ruxolitinib therapy, with abemaciclib dose escalation following a conventional 3+3 design, Bewersdorf says. At dose levels 0, 1, and 2, patients will receive twice-daily abemaciclib at 50 mg, 100 mg, and 150 mg, respectively, in continuous 28-day cycles. To isolate the effects of increasing the abemaciclib dose, the ruxolitinib dose will remain stable at 10 mg or 15 mg twice daily throughout the duration of the trial, Bewersdorf explains.

This trial is open for enrollment at Memorial Sloan Kettering Cancer Center, and enrollment at The University of Texas MD Anderson Cancer Center is also planned, Bewersdorf notes. As of April 17, 2023, 2 patients had enrolled in this trial, and neither had experienced dose-limiting toxicities.

Clinicians referring a patient to MSK can do so by visiting msk.org/refer, emailing referapatient@mskcc.org, or by calling 833-315-2722.

Videos

Jan Bewersdorf, MD, discusses the design of an ongoing phase 1 trial investigating ruxolitinib plus abemaciclib in patients with primary or secondary myelofibrosis.

Jan Philipp Bewersdorf, MD, hospital resident, Yale University School of Medicine, discusses the role of allogeneic hematopoietic cell transplant (allo-HCT) in myelofibrosis.

During the 2021 ASCO Annual Meeting, findings from a systematic review and meta-analysis of 43 studies of 8739 patients with myelofibrosis who underwent allo-HCT were presented. The analysis reported an overall survival rate of 66.7% at 1 year, 64.4% at 2 years, and 55% at 5 years.

Although the study evaluated a wide spectrum of patients with myelofibrosis who underwent allo-HCT, the analysis was not a randomized clinical trial, says Bewersdorf. Moreover, selection bias limits which patients are eligible to proceed to transplant compared with those who are ineligible because of comorbidities or fitness, Bewersdorf explains.

In this analysis, the majority of patients had higher-risk disease with Dynamic International Prognostic Scoring System scores of intermediate 2 or high-risk myelofibrosis, Bewersdorf says. The study confirmed that allo-HCT should be considered for this patient population after careful patient selection, concludes Bewersdorf. 

Jan Philipp Bewersdorf, MD, discusses the role of allogeneic hematopoietic cell transplant in myelofibrosis.  



Jan Philipp Bewersdorf, MD

Articles

Dr Bewersdorf on Ruxolitinib Plus Abemaciclib in Myelofibrosis

Dr. Bewersdorf on the Role of Allogeneic Transplant in Myelofibrosis