Examining the Early Closure of the UK SPIRIT 1 Trial

Take-aways

• Due to the unpopularity of pegylated interferon-alpha (IFN) as a treatment option for patients with chronic myeloid leukemia (CML) because of toxicities and inconvenience, the SPIRIT 1 study was terminated early after only enrolling 10.5% of the target number of patients.
• It is unlikely that the addition of pegylated IFN to imatinib for patients with newly diagnosed CML provides significant survival benefit compared with imatinib alone.
• Imatinib 400 mg daily remains the predominant first-line therapy for patients with newly diagnosed CML in the UK.

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Researchers led by Paolo Gallipoli, MB ChB, PhD, MRCP, FRCPath, from Barts Centre for Cancer Research in London, reported the outcome of the UK National Cancer Research Institute’s SPIRIT 1 trial and surveyed the reasons behind its low recruitment and early closure.

Between June 2005 and January 2009, 258 patients with newly diagnosed chronic myeloid leukemia (CML) were randomized 1:1:1 to receive one of the following treatments:

• imatinib 400 mg daily
• imatinib 800 mg daily
• imatinib 400 mg daily plus pegylated IFN at a starting dose of 90 µg/week, escalating to 180 µg/week if tolerated

The predicted sample size was 822 patients per treatment arm, with a total of 2,466 patients. However, by 2008, it was evident that recruitment was slow. When Dr. Gallipoli and colleagues surveyed clinicians as to why, they found that pegylated IFN was unpopular among patients and their physicians due to its side effects and inconvenient administration, leading to the closure of the imatinib plus pegylated IFN arm. Also, the advent of newer tyrosine kinase inhibitors (TKIs) during the follow-up period rendered the study obsolete. At the time that the trial was terminated, only 10.5% of the required number of patients had been recruited.

In the imatinib plus pegylated IFN arm, the main limiting toxicities were grade 3/4 neutropenia and low-grade fatigue/flulike symptoms. In addition, a small but not inconspicuous incidence of mood changes (mostly depression) were reported.

“The closure of SPIRIT 1 essentially brought to an end the use of pegylated IFN for the treatment of CML in the UK apart from some special circumstances such as pregnancy,” the authors wrote.

Reference

Gallipoli P, Clark RE, Byrne J, et al. The UK SPIRIT 1 trial in newly diagnosed chronic myeloid leukaemia. Br J Haematol. 2022 Jan 6. doi: 10.1111/bjh.17961. [Epub ahead of print]