Prognostic factors for complete response to ibrutinib in patients with chronic lymphocytic leukemia: A pooled analysis of 2 clinical trials

Susan M. O’Brien, Samantha Jaglowski, John C. Byrd, Rajat Bannerji, Kristie A. Blum, Christopher P. Fox, Richard R. Furman, Peter Hillmen, Thomas J. Kipps, Marco Montillo, Jeff Sharman, Sam Suzuki, Danelle F. James, Alvina D. Chu, Steven E. Coutre

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IMPORTANCE Ibrutinib, a first-in-class Bruton tyrosine kinase inhibitor taken once daily, is approved in the United States for patients with chronic lymphocytic leukemia/small lymphocytic lymphoma and allows for treatment without chemotherapy. Extended treatment with ibrutinib has demonstrated increased complete response (CR) rates over time. OBJECTIVE To analyze baseline factors that predict CR in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma treated with ibrutinib. DESIGN, SETTING, AND PARTICIPANTS Univariate and multivariate analyses of pooled data from 2 clinical trials were used to assess the prognostic value of baseline factors associated with CR in 327 patients from the PCYC-1102 and PCYC-1112 studies treated with single-agent ibrutinib. Participants were followed up in academic and community medical centers in the United States, the United Kingdom, Australia, France, Italy, Ireland, Poland, Spain, and Austria. MAIN OUTCOMES AND MEASURES Odds ratio (OR) of CR rate. RESULTS The 327 patients included in this analysis had a median age of 67 years (range, 30-86 years) and 227 (69.4%) were male. At baseline, 185 patients (56.6%) had bulky disease (lymph node 5 cm), 184 (56.3%) had advanced-stage disease, and 182 (55.7%) had an Eastern Cooperative Oncology Group performance status of 1 or higher. Thirty-one patients (9.5%) were in the first-line setting; 38 (11.6%) had undergone 1 previous therapy, 81 (24.8%) had undergone 2, and 177 (54.1%) had undergone 3 or more; patients with relapsed/refractory disease had undergone a median of 3 (range, 0-12) previous therapies. Median time on study was 26.4 months (range, 0.3-55.6 months). Thirty-two of the 327 patients (9.8%) treated with ibrutinib had a CR (PCYC-1102: relapsed/refractory, 12 of 101 [11.9%]; treatment-naive, 8 of 31 [25.8%]; and PCYC-1112: 12 of 195 [6.2%]). The median time to CR for these patients was 14.7 months (range, 4.6-47.1 months). Univariate analysis of baseline factors showed that bulky disease, clinical stage, number of previous therapies, and β2-microglobulin concentration had a significant effect on the odds of CR. The final multivariate model showed that patients with no previous therapy vs patients with at least 1 previous therapy (OR, 2.65; 95% CI, 1.01-6.95; P = .047) and patients without bulky disease (lymph node <5 cm) vs those with bulky disease (lymph node 5 cm [OR, 4.97; 95% CI, 1.91-12.91; P = .001]) had an increased likelihood of CR. CONCLUSIONS AND RELEVANCE Patients receiving ibrutinib as a first-line therapy for chronic lymphocytic leukemia and those without bulky disease had a better likelihood of CR to treatment. The CR rate with continued longer-term ibrutinib treatment was higher than in previous reports.

Original languageEnglish (US)
Pages (from-to)712-716
Number of pages5
JournalJAMA Oncology
Issue number5
StatePublished - May 2018


All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

O’Brien, S. M., Jaglowski, S., Byrd, J. C., Bannerji, R., Blum, K. A., Fox, C. P., Furman, R. R., Hillmen, P., Kipps, T. J., Montillo, M., Sharman, J., Suzuki, S., James, D. F., Chu, A. D., & Coutre, S. E. (2018). Prognostic factors for complete response to ibrutinib in patients with chronic lymphocytic leukemia: A pooled analysis of 2 clinical trials. JAMA Oncology, 4(5), 712-716.