Interferon in polycythemia vera and related neoplasms. Can it become the treatment of choice without a randomized trial?

Abstract

Recently, it was concluded that the optimal therapy for essential thrombocythemia and polycythemia vera, either recombinant interferon alpha (rIFNα) or hydroxyurea can only be determined by the completion of a randomized clinical trial. We present our recommendations for the use of rIFNα for those patients who are not candidates for the randomized trial. We argue for rethinking the approach whether we should continue to wait for the results from a randomized trial before recommending treatment with rIFNα for those unable and unwilling to enter these trials. The interferon story shows that clinical experience may be an alternative path to follow when making treatment decisions and recommendations in orphan diseases.

Keywords:

• clinical experience
• essential thrombocythemia
• hydroxyurea
• interferon
• polycythemia vera
• randomized trial

Acknowledgements

We thank Mark Crandall - a PV patient – for valuable discussions. Supported by the Cancer Research and Treatment Fund, Inc., NY, and “The Richard T Silver Myeloproliferative Neoplasm Center.”

Financial & competing interests disclosure

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Decision making on ‘optimal’ treatment of patients with orphan cancers is often compromised by the lack of the highest level of evidence, which is obtained from randomized trials, since such studies in orphan diseases are difficult to establish and conduct due to several challenges (e.g., costs to obtain an adequate number of patients at several different centers).

• Decision making on ‘optimal’ treatment of patients with orphan diseases is therefore often based upon a large number of small non-randomized clinical studies with a low impact in the scientific community, which strives for the highest level of evidence.

• In the gap between empiric and evidence-based knowledge patients with orphan diseases may become neglected while waiting for results from the randomized study.

• The interferon story in MPNs has shown that it is possible to serve patients with orphan diseases from a platform based upon empiric knowledge (clinical experience) and knowledge obtained from non-randomized studies.

• From this platform, a highly efficacious treatment with interferon has emerged during the last 25 years as assessed by common standards for treatment responses in MPNs, including normalization of blood cell counts, induction of deep (complete) molecular responses and normalization of the bone marrow.

• The superiority of rIFNα has recently been confirmed in a randomized study and will likely be substantiated in the next 5 years by results from current randomized studies comparing rIFNα with hydroxyurea in ET and PV patients.

• Low dose rIFNα is foreseen to be instituted as the cornerstone of practice from the time of diagnosis of ET, PV and hyperproliferative MF in the large majority of patients and likely in combination with JAK2 inhibitor to achieve optimal control of inflammation-mediated clonal evolution and inflammation-mediated comorbidities.

• Minimal residual disease with normalization of the bone marrow is expected in a growing number of patients who have been treated long term (>5 years) from the time of diagnosis.