Blood cancers

Ibrutinib shows promise in CNS lymphoma


Ibrutinib appears useful in the setting of primary and secondary CNS lymphoma but there is little data on the optimal way to use it in such a rare disease, Australian clinicians have found.

It will be a case of continuing to accumulate the data as the drug is used in this indication, according to findings from WA presented at ASH 2019.

An international, multicentre retrospective study of 16 patients who received the BTK inhibitor between 2015 and 2019 found the small group was very heterogeneous.

Five patients (31%) had received ibrutinib monotherapy, four (25%) received ibrutinib in combination with radiotherapy, and seven (44%) had ibrutinib in combination with a number of other systemic agents.

Total daily dose was 560mg in most patients but ranged from 420mg to 840mg.

Most of the patients (88%) had relapsed/refractory disease while two patients (12%) had received ibrutinib as part of their frontline therapy.

Most patients had also received high-dose methotrexate prior to ibrutinib.

Dr Katherine Lewis, from the department of haematology at Sir Charles Gairdner Hospital, Perth, told the limbic response rates in the real world series were surprisingly good. 

The overall response rate was 50% for primary CNS lymphoma and 88% for secondary CNS lymphoma. The complete response rates were 50% and 75% respectively. 

“It’s very promising. And certainly the duration of the response  … we’ve had 10 patients with PFS over six months. Historically, overall survival in this kind of cohort would be between two and four months,” she said.

Dr Lewis said there has been some discrepancy in the literature about whether the MYD88 mutation status mattered or not.

“There has been some data to suggest it doesn’t matter, which is interesting as you would expect that it would.”

“Anecdotally here, only two patients had it tested and both of them had that mutation and both of them got a CR with the treatment. So we think now that if we were considering putting a patient on ibrutinib we would probably test it for interest at the start.”

The study found the most common adverse events were infection (62%) and neutropenia (38%).

Dose interruptions or reductions were required in six patients due to bleeding (n=2), infection (n=1) and neutropenia (n=1).

However no invasive fungal infections were observed despite the use of high-dose dexamethasone within four weeks of starting ibrutinib or while on ibrutinib in some patients. 

“Ibrutinib demonstrated encouraging efficacy and durable responses in PCNSL and SCNSL, without unexpected toxicity, even when administered in combination regimens,” the study authors concluded.

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