Anemia-related response end points in myelofibrosis clinical trials: current trends and need for renewed consensus

Abstract

JAK inhibitors are the current standard of care in myelofibrosis, but many do not address and may worsen anemia; thus, anemia-related responses have traditionally been overlooked as efficacy end points in pivotal clinical trials, leading to a lack of consistency and analytic detail in their reporting. Here we apply our experiences in the phase III trials of momelotinib, a JAK1/JAK2/ACVR1 inhibitor and the first therapy indicated by the US FDA for myelofibrosis patients with anemia, to highlight how application of different criteria impacts the anemia-related benefits reported for any potential treatment in myelofibrosis. We advocate for a convention of a new expert consensus panel to bring consistency and transparency to the definition of anemia-related response in myelofibrosis.

Plain language summary

What is this Perspective about?

Anemia (too few healthy red blood cells) is common in patients with myelofibrosis. While it is becoming more common to measure the anemia benefits associated with potential treatments for myelofibrosis in clinical trials, different definitions of anemia benefit are available. This Perspective reviews these definitions, the differences between them, and why consistency and clarity in measuring anemia benefit matter. The definitions used in clinical trials of momelotinib, a treatment for patients with myelofibrosis and anemia, are also explained to show how the anemia benefit observed in these trials could have changed if different definitions were used.

What does this Perspective show?

Definitions of anemia benefit may include the number of red blood cell transfusions a patient receives, the amount of hemoglobin (a red blood cell protein) in their blood, or a combination thereof. Considerations such as timing, the types of patients included, and other factors are not consistent across definitions and not always clearly reported. Results when different definitions of anemia benefit were followed in the momelotinib clinical trials show that the amount of benefit observed with treatments changes depending on which definition is used.

What conclusions can be drawn from this Perspective?

More consistency and clarity in the definitions of anemia benefit in myelofibrosis clinical trials are needed, suggesting that a new panel of experts should come together to discuss this topic.

Tweetable abstract

Klencke et al. discuss the need for consensus in anemia-related response end points in myelofibrosis clinical trials, highlighting the varying definitions, key considerations, and resulting impacts on reported anemia benefits

Keywords: :

• anemia
• anemia response
• clinical trial endpoints
• clinical trials
• hemoglobin
• JAK inhibitor
• momelotinib
• myelofibrosis
• transfusion independence

Author contributions

All authors contributed to the conception, drafting, and revision of this Perspective; approved the final version; and agree to accountability for its accuracy and integrity.

Acknowledgments

We thank the patients, families, and all study investigators and site staff who participated in the momelotinib clinical trials discussed.

Financial disclosure

This work was supported by GSK. GSK and Sierra Oncology, a GSK company, were involved in data analysis and interpretation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

BJ Klencke reports employment with Sierra Oncology, a GSK company. R Donahue was an employee of Sierra Oncology, a GSK company, at the time this work was conducted. B Gorsh was an employee of GSK at the time this work was conducted, and reports stock/stock options in GSK and Daiichi Sankyo. C Ellis and B Strouse report employment with and stock/stock options in GSK. J Kawashima reports employment with Sierra Oncology, a GSK company, and stock in Gilead and GSK. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing disclosure

Writing support was provided by A Ghiretti (Nucleus Global, an Inizio company), in accordance with ICMJE and GPP guidelines and was supported by GSK.

Ethical conduct of research

This Perspective does not report original clinical trial results. For the momelotinib clinical trials discussed, the study protocols were approved by the institutional review boards of participating study sites, and all patients provided written informed consent.

Data sharing statement

For additional information or requests for access to Sierra clinical trial data for research purposes, please contact us at [email protected].

Open access

This work is licensed under the Attribution-NonCommercial-NoDerivatives 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/