On October 12, liquid biopsy was applied to follicular lymphoma for the first time to detect relapses early

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Francisco Javier Cuéllar has been very lucky.

After receiving standard treatments for his

, he relapsed;

his lymphoma was very aggressive and became very serious.

A CAR-T trial being carried out in Salamanca saved him from what seemed certain death, but not all patients have the same fortune.

Follicular lymphoma is

and indolent lymphoma (low grade and slow progression) most common.

The B lymphocytes (white blood cells) begin to malfunction and generate cancer cells, affecting mainly the lymph nodes and being able to spread through the bone marrow, spleen or even other organs.

It affects all ages, but

.

The standard first-line treatment is immunochemotherapy and

with a life expectancy of more than 20 years after diagnosis.

However,

, known as POD 24 (progression within 24 months of starting treatment),

in that space of time.

Half of them will die in the first five years.

Until now, it was impossible to identify them, to know who was going to relapse or not after receiving treatment until they got sick again after two years.

Many arrived in very poor condition, like Francisco Javier, which

(pills such as lenalidomide or the new CAR-T therapies)

and not all were saved.

But researchers from the i+12 Research Institute and the Hematology Service of the Hospital 12 de Octubre in Madrid have created a

.

The test is an analytical or

in which free circulating DNA (bits of genetic material from the tumor released into the blood) is studied.

"We have a panel with mutations and

(on average three or four), we monitor them after the treatments and those who continue to have them, even in a very small amount, are the ones that test positive and if we do not see any mutations, it is negative," he explains simply. Ana Jiménez Ubieto, main investigator of this project.

The Francisco Javier test indicates that he has made the tumor cells negative and they are going to do it every four months to see his evolution and be able to anticipate in case something goes wrong.

But the idea of ​​this test is to perform it before reaching that point, already in the first line of treatment.

"We do it in two ways:

. We have seen that after four cycles it also works, so maybe three months after starting the first treatment we could identify those patients in whom it will not work", says Jiménez Ubieto.

In this way, they could be treated differently before they get worse, give them additional treatments or extend the two years of maintenance that these patients have after receiving immunochemotherapy.

In some way it is getting closer to that

that we have been talking about for years and in which

according to mutations or how each patient responds to treatment.

"I did my thesis on follicular lymphoma and I realized that there are some patients who, whatever we do, go wrong. It occurred to me how we could identify them and there were already publications with this test in other types of lymphomas and in other types

."

In 2019, this project began to be developed with

and the first results, which are included in an article published in the journal

(

) and signed by this specialist and by the researcher Santiago Barrio, show that the test has a 95% sensitivity.

"Now we have more than 100 patients, but the publication focuses on 87.

, in 5% we do not see them and we cannot use the test. It may be because bad samples have been acquired or because it has a different phenotype... We don't know, it's one of the things we're trying to improve," says Jiménez Ubieto.

This type of test had never been used for this lymphoma.

In fact, "

, we are the first group that has managed to do it."

The work was published on January 3 and only one day later another article on follicular lymphoma was published in the

journal , precisely by another Spanish group.

"They are colleagues from the Puerta de Hierro Hospital, in fact, we are joining forces to work along the same lines and they

," says Jimenez Ubieta.

The specialist specifies that the test used by both groups is very similar but has some differences.

Future applications of the test

In its second phase (the one that they are developing now and in which Francisco Javier is), the project consists of

-CAR-T and bispecific antibodies- .

"Our next objective, in addition to performing this test on these other therapies, is to try to develop a clinical trial where we treat these patients more intensively to see if their prognosis improves and they do not relapse," says the specialist.

But it is not the only idea that they want to develop.

The test has

, as Jiménez-Ubieto explains: "With a PEC-CT test we see the response of lymphomas, as of almost all tumors, but sometimes they are false positives because, for example, patients present masses that are for something else and we cannot biopsy them. With this test, a simple analysis,

. Another application is to

or to see

after a period of treatment".

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