CAR-T therapy 'jumps' to frontline in high-risk lymphoma trial

• Salud CART, the therapies of the future against cancer that erase it in the present

Starting the treatment of certain patients with lymphoma with CAR-T cell therapy instead of conventional treatment could be a near reality, according to the results of a

, still in

, but which provides encouraging data in that direction.

That trial, published today in

, shows that advancing CAR-T cell treatment to

achieves a

of 37 patients with high-grade large B-cell lymphoma (LBDC). risk and an

at twelve months of

.

The therapy that uses the patient's autologous T lymphocytes modified with a chimeric antigen receptor (CAR) to selectively direct them towards the CD19 surface protein of cancerous B cells has been successfully used for years in a group of patients for whom there were no longer therapeutic options .

But everything indicates that the CAR-T cells are not going to remain in the redoubt of the

.

Recently, two randomized clinical trials have made it clear that two CD19 CAR-T treatments that are already being used in the clinic (axicabtagene ciloleucel and lysocabtagene) are more beneficial than standard second-line treatment (chemotherapy and autologous transplant) in patients with LBDCG.

With the new study published today Monday, one of these treatments, axicabtagén ciloleucel (

) also seems to provide a

administered in

.

The data even indicate that chemotherapy could be left aside and give way to this CAR-T in the treatment of certain

.

This is the hope of the main author of the trial,

deputy director of the Department of Lymphoma and Myeloma at the University of Texas MD Anderson Cancer Center (Houston), who tells Diario Médico that "we believe that the results of the study indicate that

, but this needs to be confirmed in a randomized trial."

patients have been included in the study

, which implies both those with an

or

[international prognostic index used in lymphomas]

, as well as those with certain

that are especially aggressive and proliferative, such as

or

lymphoma .

These are patients who have lower than usual response rates to standard chemoimmunotherapy, as well as lower overall and progression-free survival.

Attempts have been made to intensify these treatments in order to achieve better results, but without success;

in fact, it is estimated that

achieve

long-term disease

New option in patients with poor prognosis

The now-published trial, called

, "is the first study evaluating CD19-directed CAR T-cell therapy as part of first-line treatment for DLBCL specifically targeting patients with this type of lymphoma of the high risk who have a

", explains the onco-hematologist to this newspaper.

Forty high-risk DLBCL patients who received axi-cel were included in the study.

Ninety -five percent had

, 25% had

score equal to or greater than 3

.

The treatment was

, with the known safety profile of this therapy.

The results of the study "indicate that axi-cel is

in these high-risk DLBCL patients with an

and a

. After a

-up of about

,

," highlights Professor Neelapu.

"This is quite remarkable in two ways: first because the greater than 70% duration is

in these patients (less than 40% expected durability with standard therapy) , and secondly, because axi-cel induces durable responses in approximately 40% of patients administered in second and third lines.However, when used in first-line therapy in this study, durable responses of the patients greater than 70%, suggesting that

.

Although follow-up is short, it is very likely that most patients who continue to respond beyond one year will be cured of their lymphoma."

In conclusion, for the specialist, "the results of the ZUMA-12 study indicate that the treatment of high-risk patients with axi-cel

, but it must be

in a randomized

trial ."

Less treated lymphocytes: more powerful

Another of the observations of the work concerns the functional capacity of the lymphocytes used in previous lines, as they come from patients less exposed to the toxicity of other treatments.

Neelapu comments: "We expected that T cells were likely to be less dysfunctional in patients in first line compared to third line and beyond. Consequently, we found that the

the

product , which is associated with greater expansion and efficacy of CAR-T cells, was

in the ZUMA-12 study in the first-line setting compared to the ZUMA-1 study in the third-line setting, suggesting

in first-line treatment.

Axi-cel induces durable responses in approximately 40% of patients in the second and third lines.

However, when used as part of the first-line treatment in this study, durable responses were seen in more than 70% of patients, suggesting that the efficacy of axi-cel may be much greater when used as a first-line treatment. first line

."

Neelapu's team plans to continue the

-up study to confirm the duration of the patients' response to axi-cel.

stress ,

will be needed

to definitively demonstrate whether CAR-T cell therapy is more effective for high-risk DLBCL patients than chemoimmunotherapy, the standard of care.

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