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FDA review summary of patient-reported outcome results for ibrutinib in the treatment of chronic graft versus host disease

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Abstract

Purpose

On August 2, 2017, the Food and Drug Administration approved ibrutinib (IMBRUVICA) for the treatment of patients with chronic graft versus host disease (cGVHD) after the failure of one or more lines of systemic therapy. The approval was based on results from a single-arm, multicenter trial that enrolled patients with refractory cGVHD. This paper describes the FDA review of patient-reported outcomes (PRO) data from Study PCYC-1129-CA and the decision to incorporate descriptive PRO data in the FDA label to support the primary clinician-reported outcome results.

Methods

In this trial, the Lee Chronic GVHD Symptom Scale (LSS) was used to capture patient-reported symptom bother. The 42 patients who received treatment were included in the analysis and completed the PRO tool. Post hoc descriptive analyses were conducted to further understand the measurement properties of the LSS.

Results

The analysis submitted to FDA reported that 18 patients had a ≥ 7-point improvement on the LSS overall summary score at any point during the assessment period. For 10 patients, the ≥ 7-point improvement was sustained for ≥ 2 consecutive PRO assessments. An assessment of the responder threshold suggested the threshold submitted to the FDA was reasonable and in line with clinical findings.

Conclusions

Overall, study PCYC-1129-CA demonstrated favorable clinician-reported cGVHD efficacy results that were complemented by results from PRO data, supporting the FDA’s positive benefit-risk assessment leading to regular approval. Limitations included the single-arm trial design, responder definition, and instrument shortcomings. These limitations were thoroughly explored through additional FDA post hoc analyses.

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Authors and Affiliations

  1. Oncology Center of Excellence, U.S. Food and Drug Administration, Building 22, 10903 New Hampshire Avenue, Silver Spring, MD, 20993, USA

    Bellinda L. King-Kallimanis & Paul G. Kluetz

  2. Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, USA

    Tanya Wroblewski, Virginia Kwitkowski, R. Angelo De Claro, Thomas Gwise, Vishal Bhatnagar & Ann T. Farrell

  3. U.S. Food and Drug Administration, WO22 Room 2372, 10903 New Hampshire Avenue, Silver Spring, MD, 20993, USA

    Bellinda L. King-Kallimanis

Authors
  1. Bellinda L. King-Kallimanis
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  2. Tanya Wroblewski
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  3. Virginia Kwitkowski
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  4. R. Angelo De Claro
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  5. Thomas Gwise
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  6. Vishal Bhatnagar
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  7. Ann T. Farrell
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  8. Paul G. Kluetz
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Contributions

BKK, TG, ADC, VK and PK designed the research, BKK and ADC conducted analyses, TW, TG, AF and PK provided oversight for the analyses, BKK, TW, VK, ADC, VB, AF and PK wrote the manuscript.

Corresponding author

Correspondence to Bellinda L. King-Kallimanis.

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Conflict of interest

The authors declare no competing financial interests.

Ethical approval

IRB: This is US Government work and is a secondary analysis of data that was submitted to the Food and Drug Administration, therefore, IRB was not applicable. The trial identifier is NCT02195869.

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King-Kallimanis, B.L., Wroblewski, T., Kwitkowski, V. et al. FDA review summary of patient-reported outcome results for ibrutinib in the treatment of chronic graft versus host disease. Qual Life Res 29, 1903–1911 (2020). https://doi.org/10.1007/s11136-020-02448-y

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  • DOI: https://doi.org/10.1007/s11136-020-02448-y

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