Blood cancers

Study shows when to use methotrexate with R-CHOP in diffuse large B-cell lymphoma

New data will help clinicians choose between offering high-dose methotrexate in between or after R-CHOP therapy in patients with diffuse large B-cell lymphoma (DLBCL) at risk of CNS relapse, UK researchers say.

A retrospective study compared intercalated therapy with end of treatment therapy in 334 patients undergoing R-CHOP chemotherapy, and found that both may be valid in the right circumstances.

In results presented at the 2020 European Hematology Association (EHA 2020) virtual meeting, they showed that in the just over 200 patients who had intercalated methotrexate therapy, 20% had a delay in their next R-CHOP cycle with a median delay of 7 days. In 14% of cases it was judged by the clinician that the methotrexate had directly attributed to the delay.

The researchers at Glasgow’s Beatson West of Scotland Cancer Centre also reported that there was an increased risk of toxicity, notably mucositis and neutropenic fever, associated with intercalated doses of methotrexate.

But further analysis showed that the risk of delay was much less when intercalated methotrexate was given early after R-CHOP.  The greatest overall increased risk of delay was seen in patients who had the intercalated methotrexate on day 10 or more post R-CHOP (odds ratio 1.74 [1.03-2.93]).

There was no difference in survival between groups or in CNS relapse rate, which suggests that either approach can be considered if you take into account the competing risks for the individual, the researchers concluded.

Speaking with the limbic, study leader Dr Matt Wilson, a specialist registrar in haematology, said they set the study up to look at the question of whether intercalated therapy caused a delay in R-CHOP rather than to investigate whether giving methotrexate is an effective strategy overall. But that said, they couldn’t detect any difference in survival or CNS relapse.

“When we looked at survival and relapse the event rate was low, just under 6%, and these are the patients at the highest risk,” he said.

“Although we have not been able to say whether one is superior to the other, we have shown that both are still valid – and rather than having a blanket policy it is about taking a patient on an individual basis and deciding what’s the best approach for them.”

Dr Wilson said that if a patient was young and fit with a high risk of CNS relapse there is a good rationale for opting for intercalated therapy.

“I think what we will probably change going forward is in patients where we are a bit worried about their fitness and the risk of toxicity we will wait and give [methotrexate] at the end.”

He cautioned that there were other caveats to the research including that it was a retrospective analysis.

“But what we have shown is that we can deliver intercalated methotrexate without significant delays especially if you give it early between the two cycles, before day 10.”

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