Blood cancers

CNS relapse a neglected area of lymphoma management

The value of assessing the risk of CNS relapse in lymphoma and providing CNS-directed prophylaxis for at-risk patients remains underappreciated.

According to a ‘How I Treat’ article in Blood, there is also no consensus around optimal dose, timing or route of prophylactic therapy.

Dr Chan Cheah, from the Sir Charles Gairdner Hospital in WA, told the limbic that clinical practice was not uniform.

“At large centres there is a fairly uniform adoption of trying to do something extra after standard treatment to prevent CNS relapse,” he said.

“But it’s far from standard and I see people who are clearly at high risk of CNS relapse who were not given any prophylaxis.”

“Large cell lymphoma is the most common form of lymphoma that we see and 20 to 30% of patients will be at high risk for CNS progression so it’s actually not that rare.”

Dr Cheah said there was good data now to identify patients might be at high risk.

More controversial was the limited evidence for whether prophylaxis actually worked.

“The majority of people around the world agree that some form of high dose methotrexate is probably required. This is completely different to standard R-CH0P, which is what most people get as a primary treatment modality.”

The article included several case vignettes drawn from his practice highlighting some of the challenges around assessment and prophylaxis.

For example, he said he would offer prophylaxis to DLBCL patients with breast, uterine, testicular and epidural involvement even if their CNS-IPI was low.

There was also evidence that patients with MYC, BCL2 and BCL6 rearrangements were at high risk of CNS involvement.

Dr Cheah said rituximab had slightly decreased the risk of CNS relapse by generally improving systemic outcomes.

Lenalidomide and ibrutinib were also showing some promise for the future.

“Both agents cross the blood-brain barrier and are effective in primary CNS lymphoma so they will probably reduce the incidence of CNS relapse if they are incorporated into frontline treatment,” he said.

Until then methotrexate dosing was typically 3-3.5g/m2 although that may not feasible in all patients including the elderly.

“We know that about one in six people with high dose methotrexate will develop renal failure as a consequence and we can’t predict who that will be.”

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