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CAR-T therapies have proven effective. A few years ago they began as a rescue resource for those malignant blood tumors against which there was nothing that could erase them from the body. With the passage of time, little by little, they no longer seek to be that last option, but one more in the therapeutic arsenal against cancer.

However, clinicians and researchers have an arduous task ahead of them. Proving that an expensive therapy is better, that is, much better than the current possibilities takes time (and money). Without being the usual forum for the communication of advances in Hematology, given that this medical specialty has its own annual appointment promoted by the American Association of Hematology (ASH), at the Congress of the American Society of Medical Oncology (ASCO) a special session has been dedicated on the last day to the needs of advanced therapies.

And in this symposium, as a late-break abstract (studies that are presented at the last minute), data have been made public showing that CAR-T therapy (specifically the so-called axicabtagene ciloleucel) is the best option as a second-line treatment in diffuse large B cell lymphoma. That is, if the plan to address this malignant blood cancer is first the 'chemo', then another more aggressive 'chemo' and a bone marrow transplant, to reach advanced therapy at the end, it can advance to the second step.

This is how advanced therapies advance


CAR-T therapy 'jumps' to the front line in high-risk lymphoma trial

  • Writing: SONIA MORENO Madrid

CAR-T therapy 'jumps' to the front line in high-risk lymphoma trial


No trace of Alyssa's cancer, the visible face of the new generation of CAR-T therapies

  • Writing: CRISTINA G. LUCIO Madrid

No trace of Alyssa's cancer, the visible face of the new generation of CAR-T therapies

Ana Sureda, one of the authors of the ZUMA-7 study also published today in The New England Journal of Medicine, explains that "approximately 60% of patients with diffuse large cell lymphoma (LDCGB) are cured with first-line treatment. This percentage depends in part on the risk group in which the patient is diagnosed." Therefore, he points out that "those patients with more factors of poor prognosis at diagnosis have lower chances of cure with first-line treatment than those patients who have a lower number of these factors."

LDCBG makes up 35% of non-Hodgkin lymphomas and its incidence increases with age. It is an aggressive histological subtype that requires rapid initiation of treatment once it has been diagnosed.

The work presented at ASCO and published in the NEJM states that "at the follow-up time of about 47.2 months, axi-cel [the acronym for axicabtagene ciloleucel therapy] as a second-line treatment for patients with refractory or early-relapse LDCBG demonstrated significantly longer overall survival than that offered by standard treatment."

Note that what is significant here translates into a 27.4% reduction in the risk of death, which corresponds to a 38% relative improvement in overall survival, despite the fact that 57% of patients who were treated within the trial with standard treatment then receive cell therapy outside the protocol. Sureda points out that "while patients included in the clinical trial and treated with axicel had an event-free survival of approximately 40%, this was less than 20% in the conventional treatment group."

First treatment in almost 30 years that improves survival compared to standard treatment

At ASCO, Jason Westin, principal investigator of ZUMA-7 and director of Lymphoma Clinical Research and Associate Professor in the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center, has been commissioned to disclose the data. "This is the first treatment in nearly three decades that significantly improves overall survival in patients with primarily refractory or early-relapsed LDCGB and will undoubtedly change the SOC [current standard of care] in this patient population," he says.

Sureda explains why this step announced now is key. "Patients who are primarily refractory or in early relapse (in the first 12 months) have a very poor long-term prognosis and the results with autologous transplantation do not exceed 20% of patients alive and free of disease. These patients are an unmet medical need and will now be able to benefit from the introduction of axi-cell in this area." Westin adds, "The totality of the ZUMA-7 data is compelling for axio-cel to be used as soon as patients with large B-cell lymphoma relapse or do not respond to first-line treatment."

Another advantage highlighted by the researchers is that the safety profile has not changed. Side effects are similar to those already known in previous studies and no new treatment-related deaths occurred since the primary analysis of event-free survival (SLE). The main analysis of showed that grade 3 or higher adverse effects occurred in 91% of patients treated with axi-cel, compared with 83% of those treated with standard treatment. Among the most frequent are neutropenia (69% versus 41%, respectively), anemia (30% versus 39%) and leukopenia (29% versus 22%).

Demonstration of face-to-face effectiveness with other therapeutics

The oncologist, also head of the Department of Hematology and Hematopoietic Progenitor Cell Transplantation Program of the Catalan Institute of Oncology, explains that "there are two prospective phase 3 clinical trials that randomize in a 1-to-1 ratio patients with diffuse large B cell lymphoma primarily refractory or in early relapse to receive either a second-line rescue chemotherapy and subsequent consolidation with an autologous transplant or to receive an autologous anti-CD19 CART. These assays are ZUMA-7 (the CAR-T used is axicabtagene ciloleucel) and the TRANSFORM assay (the CAR-T used is lysocel maraleucel)."

In this way, clinicians can examine the validity of choosing an advanced therapy against an already standardized or scheduled treatment. "Both ZUMA-7 and TRANSFORM showed that the rate of objective responses and complete remissions, as well as event-free survival, was better in patients treated with CAR-T cells than in patients treated with conventional treatment," Sureda said.

Axi-cel is approved by both the FDA and the EMA (regulatory agencies in the US and Europe, respectively) and is already being used in real life in the US and some European countries). Liso-cel (an acronym for lisocel maraleucel) is approved by the FDA and has received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP). As Sureda explains, "patients with primarily refractory or early-relapsed disease may already benefit from this new therapeutic strategy."

  • cancer
  • Advanced therapies
  • Articles Pilar Pérez

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