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Ibrutinib combo advances in CNS lymphoma

Grommes C et al. Blood. 2019;133(5):436-45.

Key clinical point: Combination ibrutinib, rituximab, and high-dose methotrexate showed a favorable response in patients with recurrent/refractory CNS lymphoma.

Major finding: The ibrutinib-based regimen showed an 80% overall response rate; no grade 5 adverse events were reported.

Study details: A phase 1b study of 15 patients with recurrent/refractory CNS lymphoma.

Disclosures: The study was supported by grant funding from Pharmacyclics to Memorial Sloan Kettering. The authors reported financial ties to AstraZeneca, Bristol-Myers Squibb, BTH, Kite Pharma, Pfizer, and others.

Read the Article.

Citation:

Grommes C et al. Blood. 2019;133(5):436-45.

Commentary:

Dr. David Henry, Editor in Chief of MDedge Hematology/Oncology, comments:

Based on the success of ibrutinib in aggressive B-cell non-Hodgkin lymphoma, Dr. Grommes and colleagues from Memorial Sloan Kettering studied ibrutinib at a maximum dose of 840 mg daily, methotrexate 3.5 g/m2 IV every other week for a total of eight infusions, and rituximab 500 mg/m2 every 2 weeks. Ibrutinib was held on the days of high-dose methotrexate.

At a median follow up of 19.7 months, the authors report an 80% overall response rate with a median progression free survival in all 15 patients of 9.2 months, and a median overall survival not yet reached, with 11 of 15 patients still alive. The most frequent adverse events were cytopenias and mild transaminase elevations. Interestingly, at this dose of ibrutinib, the authors saw no atrial fibrillation or bleeding.

While this is an interesting and very encouraging study outcome in a difficult-to-treat population of CNS lymphoma, the regimen will need to be compared to another rather impressive reported regimen of rituximab, high-dose methotrexate, and temozolomide (Blood. 2009;114:1672).

Notably, the current report by Dr. Grommes and colleagues did not include any HIV patients, where there is also a great need for an effective regimen. However, given the success that ibrutinib now enjoys in aggressive B-cell lymphomas, this regimen is attractive for its simplicity and mechanism of action. We await further study updates with enthusiasm.