The results of a prospective, multicenter, phase 2 study of patients with relapsed or refractory primary central nervous system (CNS) lymphoma or primary vitreoretinal lymphoma suggested that treatment with ibrutinib — an irreversible selective inhibitor of Bruton tyrosine kinase — showed clinical activity in the brain, the cerebrospinal fluid, and the intraocular compartment.1

For the study, researchers recruited 52 patients with relapsed or refractory primary CNS lymphoma or with primary vitreoretinal lymphoma. The investigators administered 560 mg of ibrutinib daily, in 28-day cycles, until disease progression or unacceptable toxicity occurred. Of all patients, 14 also received corticosteroids during the first month of treatment.

The primary study end point was the disease control rate after 2 cycles (2 months) of treatment. The researchers also assessed complete response rate after 4, 6, 9, and 12 cycles of treatment; overall survival; progression-free survival; and toxicity.

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The researchers collected cerebrospinal fluid samples via lumbar puncture before patients received the first dose of treatment on day 1 and again right before treatment was administered on day 29. The investigators also extracted DNA from tumor samples taken from the initial diagnostic brain biopsies to determine the status of MYD88, CD79b, and CARD11 somatic mutations.

The researchers were able to evaluate 44 patients for the primary end point. After 2 months of treatment, the disease control rate was 70% in evaluable patients and 62% in the intent-to-treat analysis. The overall response rate in evaluable patients was 59% and 52% in the intent-to-treat analysis. The treatment failed in 13 (29%) of all evaluable patients and 20 (38%) patients included in the intent-to-treat analysis.

The disease control rate after 4, 6, 9, and 12 cycles of treatment was 39%, 32%, 32%, and 27%, respectively. The overall response rate was 39%, 27%, 29%, and 25%, respectively.

At a median follow-up of 25.7 months, the median progression-free survival was 4.8 months, whereas the overall survival was 19.2 months. According to the results of the ITT analysis, the median progression-free survival was 3.3 months and overall survival was 14.4 months.

The researchers were able to detect ibrutinib in all cerebrospinal fluid samples that were tested at a steady state, finding that the mean concentration of the drug in cerebrospinal fluid was 0.23 ng/ml (0.52 nM) (range, 0.2–0.84 ng/ml).