CAR-T therapies have proven their efficacy. 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.. Demonstrating that an expensive therapy is better, that is, much better than 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 meeting promoted by the American Association of Hematology (ASH), the Congress of the American Society of Medical Oncology (ASCO) has dedicated a special session 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 that show that CAR-T therapy (specifically the so-called axicabtagene ciloleucel) is the best treatment option second-line therapy for diffuse large B-cell lymphoma. In other words, if the plan to address this malignant blood cancer is first 'chemo', then another more aggressive 'chemo' and a bone marrow transplant, to arrive at advanced therapy at the end, this may overtake the second step.

Ana Sureda, one of the authors of the ZUMA-7 study, which is also published today in The New England Journal of Medicine, explains that “approximately 60% of patients with diffuse large cell lymphoma (GBCL) are cured with first-line treatment.” line. This percentage depends in part on the risk group in which the patient is diagnosed.”. For this reason, he specifies that “those patients with more poor prognostic factors at diagnosis have less chance of cure with first-line treatment than those patients who have fewer of these factors.”

GBDL constitutes 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 a 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 relapsed DLBCL Early treatment demonstrated significantly longer overall survival than that offered by standard treatment.”

Bear in mind that what is significant here is translated into a 27.4% reduction in the risk of death, which corresponds to a relative improvement of 38% in overall survival, despite the fact that 57% of patients who were treated within the trial with standard treatment and then received off-protocol cell therapy. Sureda points out that “while the 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 group with conventional treatment.”

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

At ASCO, Jason Westin, Principal Investigator for 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 reveal the data.. “This is the first treatment in almost three decades to significantly improve overall survival in patients with primary refractory or early relapsed GBDL, and it will undoubtedly change the [current standard of care] SOC 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 results with autologous transplantation do not exceed 20% of patients alive and free of disease.. These patients constitute an unmet medical need and can now benefit from the introduction of axi-cell in this area”. And in this sense, Westin adds that “the totality of the ZUMA-7 data is convincing for axi-cel to be used as soon as patients with large B-cell lymphoma relapse or do not respond to first-line treatment.”

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

Demonstration of face-to-face effectiveness with another therapeutic

The oncologist, also head of the Department of Hematology and the Hematopoietic Stem Cell Transplant Program of the Catalan Institute of Oncology, explains that “there are two prospective phase 3 clinical trials that randomize patients with diffuse large B-cell lymphoma 1:1 primarily refractory or in early relapse to receive either second-line salvage chemotherapy and subsequent consolidation with autologous transplantation or to receive anti-CD19 autologous CART. These assays are the 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 test the validity of choosing an advanced therapy compared to an already standardized or prescribed 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 those patients treated with CAR-T cells than in those patients treated with conventional therapy,” Sureda points out.

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 can already benefit from this new therapeutic strategy.”