Harry Gill, MD, FRCP, FRCPath, clinical assistant professor, Department of Medicine, Li Ka Shing Faculty of Medicine, Hong Kong University of Medicine, discusses updated efficacy data and analysis of genomic characteristics of response with ropeginterferon alfa-2b(P1101) in primary myelofibrosis.

An ongoing multicenter phase 2 study (NCT04988815) was designed to assess the efficacy and safety of this next-generation monopegylated interferon in patients with early or pre-fibrotic myelofibrosis and those with low- or intermediate-1 risk myelofibrosis according to the Dynamic International Prognostic Scoring System. A total of 65 patients were enrolled in the trial. Patients were treated with a starting dose of 250 mcg of ropeginterferon alfa-2b, which was increased to 350 mcg at week 2 and 500 mcg biweekly beginning at week 4.

The primary end points were hematologic response at 24 and 48 weeks and adverse effects (AEs). Key secondary end points included changes in allele burden of driver and non-driver gene mutations, quality of life, cytokine profiles and bone marrow morphology.

Results showed that 76.3% and 83.1% of all patients achieved hemoglobin and white blood cell (WBC) count responses, respectively, with ropeginterferon alfa-2b at 24 weeks, and 76.3% experienced platelet responses, Gill reports. These rates were 83.0%, 83.0%, and 72.3% at 48 weeks. Responses were early, and hemoglobin, WBC and platelet levels remained stable, Gill says. Moreover, no thrombotic events were observed, Gill adds.

Regarding molecular responses, 76% of patients with 

 mutations experienced reductions in mutant allele frequency at 6 months, Gill continues. Of these, 26% of patients with 

 mutations experienced a 50% or greater reduction. Notably, 8% of patients with 

 V617F mutations achieved a complete molecular response, Gill emphasizes.

Regarding safety, the agent was well tolerated, he states. Additionally, no deaths, transformation to AML, or vascular events were reported. Five patients discontinued treatment.

These findings indicate that early administration of ropeginterferon alfa-2b is safe, active, and may allow for disease modification, Gill concludes.

Videos

Harry Gill, MD, FRCP, FRCPath, discusses updated efficacy data and analysis of genomic characteristics for ropeginterferon alfa-2B in primary myelofibrosis.

Dr Gill on the Efficacy and Genomic Features of Ropeginterferon Alfa-2B in Myelofibrosis  

Harry Gill, MD, FRCP, FRCPath, clinical assistant professor, Department of Medicine, Li Ka Shing Faculty of Medicine, Hong Kong University of Medicine, discusses the investigation of an all-oral combination of arsenic trioxide, all trans retinoic acid (ATRA), and ascorbic acid (the AAA regimen) in patients with newly diagnosed acute promyelocytic leukemia (APL).

Data from the phase 2 APL003 trial (NCT04687176) presented at the 2023 EHA Congress showed that all 98 patients evaluable for efficacy experienced a complete remission, according to Gill. Through the study and follow-up period, only 1 patient relapsed and later died from refractory APL. Gill says this relapse was due to a 

A216V mutation, which conferred resistance to arsenic trioxide.

Additional data showed that the 3-year relapse-free survival (RFS) rate was 97.1%, and the 3-year overall survival (OS) rate was 98.9%. 

Regarding safety, the most common non-hematologic adverse effects (AEs) included transaminitis (55%) and headache (33%), and those toxicities were all grade 1/2. Notably, no cardiotoxicity or grade 3/4 hepatoxicity related to oral arsenic trioxide were reported. Additionally, no treatment-related deaths occurred, and arsenic trioxide did not lead to any treatment discontinuations. APL differentiation syndrome was reported in 60% of patients within 14 days of the initiation of AAA; all of these patients fully responded to dexamethasone.

The ongoing single-arm study is enrolling patients with newly diagnosed APL with t(15;17)(q24;q21) or acute myeloid leukemia harboring variant RARA translocation, per 2022 World Health Organization Classification. During induction, patients received 10 mg of arsenic trioxide per day plus 45mg/m

 of ATRA in 2 divided doses and 1 g of ascorbic acid per day for 42 days. In patients under 18 years of age, the doses were 0.16 mg/kg per day for arsenic trioxide, 25 mg/m

 per day of ATRA, and 15 mg/kg per day for ascorbic acid.

Consolidation therapy consisted of AAA daily for 14 days every 28 days for 2 cycles, and AAA was then given as maintenance therapy for 2 weeks every 8 weeks for up to 2 years, totaling 12 cycles. RFS and event-free survival serve as the trial’s co-primary end points. OS and toxicities are secondary end points. Recruitment in a multicenter setting in Asia is ongoing.

Harry Gill, MD, FRCP, FRCPath, discusses the investigation of an all-oral combination of arsenic trioxide, all trans retinoic acid, and ascorbic acid in patients with newly diagnosed acute promyelocytic leukemia.

Harry Gill, MD, FRCP, FRCPath

Articles

Dr Gill on the Efficacy and Genomic Features of Ropeginterferon Alfa-2B in Myelofibrosis

Dr Gill on the Evaluation of Oral Arsenic Trioxide Plus ATRA/Ascorbic Acid in APL