Javier Pinilla-Ibarz, MD, PhD: Use of Bruton's Tyrosine Kinase Inhibitor

What phase III data support the use of a Bruton’s tyrosine kinase inhibitor in this patient?

The Resonate trial tested the use of ibrutinib against ofatumumab, another monoclonal antibody against CD20, already approved in the US for relapsed and refractory CLL, in a very large portion of patients who had relapsed disease. This trial demonstrated that patients had a long PFS and increase of OS in comparison with the ofatumumab arm. On top of that, these responses are independent of the presence of 17p deletion, or other bad prognostic markers, that may give a different kind of outcome in the long run.

Case 1: Relapsed and Refractory CLL

Robert is a 63-year-old retired civil engineer from Houston, Texas. His medical history is notable for mild hypertension and for an acute appendicitis and appendectomy in 2010. He presented to his PCP in September 2012 with symptoms of intermittent fatigue and abdominal discomfort.

On physical examination, Robert showed moderate splenomegaly (12 cm), lymphadenopathy, and CBC showed elevated WBC count of 98 x 109/L, with 80% lymphocytes, and anemia (Hb 11 g/dL).

He was referred to an oncologist for further evaluation and was subsequently diagnosed with (CLL); peripheral blood flow cytometry showed mature B lymphocytes CD5+/CD23+.

Interphase cytogenetic analysis showed 17p13.1 deletion

He was initiated on chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab (FCR) in October 2012

After 5 cycles he displayed a complete response, with disappearance of palpable disease, normalization of blood counts, and no evidence of disease on bone marrow biopsy and CT scans.

In January 2015, he presented to his oncologist with symptoms of worsening fatigue and abdominal distension.

• On relapse he shows bulky disease 5.5 cm; Hb 12 g/dL, platelets 120,000 cells/mm3, lymphocytes 39,000/mm3, and beta 2 microglobulin of 4.1 mg/L
• His ECOG performance status at the time of recurrence was 1, and liver and kidney function were within normal limits