Ibrutinib Active in Previously Untreated and Relapsed/Refractory CLL With TP53 Aberrations


Key Points

  • Ibrutinib produced response in 97% of previously untreated patients and 80% of those with relapsed/refractory disease.
  • Treatment-related grade 3 or 4 adverse events included neutropenia in 24%, anemia in 14%, and thrombocytopenia in 10%.

In a phase II study reported in The Lancet Oncology, Farooqui et al found that single-agent ibrutinib (Imbruvica) had good activity in patients with previously untreated or relapse/refractory chronic lymphocytic leukemia (CLL) with TP53 aberrations.

Study Details

In this single-arm trial, 51 adult patients enrolled between December 2011 and January 2014 at the National Institutes of Health Clinical Center received ibrutinib 420 mg once daily in 28-day cycles until disease progression or limiting toxicities. The TP53 alteration was deletion 17p13.1 in 47 and TP53 mutation in the absence of deletion 17p13.1 in 4. CLL was previously untreated in 35 and relapsed/refractory in 16.

Response Rates

Median follow-up was 24 months. Among 33 previously untreated patients evaluable for response at 24 weeks, the response rate was 97% (95% confidence interval [CI] = 86%–100%), including partial response in 55% and partial response with lymphocytosis in 42%. One patient (3%) had progressive disease at 0.4 months. Among 15 patients with relapsed/refractory disease evaluable for response at 24 weeks, the response rate was 80% (95% CI = 52%–96%), with partial response in 40% and partial response with lymphocytosis in 40%. The remaining three patients (20%) had stable disease.

Estimated progression-free survival and overall survival on an intention-to-treat basis at 24 months was 82% and 80% among all patients, including 91% and 84% in previously untreated patients and 80% and 74% in those with relapsed/refractory disease.

Adverse Events

The most common treatment-related adverse events of any grade were arthralgia (59%), diarrhea (51%), rash (47%), and nail ridging (43%). The most common treatment-related adverse events of grade ≥ 3 were neutropenia (24%, grade 4 in 2%), anemia (14%), thrombocytopenia (10%, grade 4 in 2%), and pneumonia (6%).

The investigators concluded: “The activity and safety profile of single-agent ibrutinib in CLL with TP53 aberrations is encouraging and supports its consideration as a novel treatment option for patients with this high-risk disease in both first-line and second-line settings.”

Adrian Wiestner, MD, of Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, is the corresponding author for The Lancet Oncology article.

The study was funded by the Intramural Research Program of the National Heart, Lung, and Blood Institute and the National Cancer Institute, Danish Cancer Society, Novo Nordisk Foundation, National Institutes of Health Medical Research Scholars Program, and Pharmacyclics Inc. For full disclosures of the study authors, visit

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