Stem Cell Transplants Improves Survival Without Progression in Relapsed LBCL Subset

Autologous hematopoietic cell transplantation (auto-HCT) resulted in lower relapse rates and improved rates of survival without disease progression compared with CAR-T cell therapy in patients with relapsed large B-cell lymphoma (LBCL) who were in complete remission (all signs and symptoms of cancer are gone), according to recent study results.

Findings from this study were presented at the 2023 ASH Annual Meeting.

According to the National Cancer Institute, auto-HCT refers to a procedure when a patient’s healthy stem cells are collected from bone marrow or blood before treatment, stored, then returned to the patient after treatment. With CAR-T cell therapy, a patient’s T cells are genetically modified in a laboratory, allowing them to bind to antigens on cancer cells and eliminate them.

“The message here is that this data could be practice informing and also confirming,” Dr. Mazyar Shadman, associate professor in the Clinical Research Division and Innovators Network Endowed Chair at Fred Hutch Cancer Center in Seattle, said during a presentation of the data. “Patients who relapse after first-line therapy after 12 months, the current standard of care is to receive salvage therapy (treatment given after the disease does not respond to other therapies) with (autologous) transplant and this data confirmed that.”

Shadman added that currently there are no data suggesting that patients who are in complete remission should receive CAR-T cell therapy in the setting of relapse after 12 months. Although, he said, in patients with primary refractory disease (not achieving a complete response to any therapy and not being in partial remission), the goal of therapy should be CAR-T cell therapy.

“All the efforts should be done to improve access to CAR T,” he said. “But until then, for patients who achieve a good clinical response, namely complete response, an (autologous) transplant strategy could be a reasonable option to discuss with the patient and could add another potential curative therapy for these patients, knowing that CAR T could still be utilized in the later line of therapy if (autologous) transplant fails the patient.”

Improved PFS and Relapse Rates

In the analysis, the two-year progression-free survival (PFS; the time during and after treatment when a patient with cancer lives without disease worsening) rate was 66.2% in patients who underwent auto-HCT compared with 47.8% in those who received CAR-T cell therapy across the entire cohort. The auto-HCT group also had a lower relapse rate at two years compared with the CAR-T cell therapy group (27.8% versus 48%).

In addition, patients who underwent auto-HCT demonstrated a higher overall survival (OS; the time from the start of treatment that a patient with cancer is alive) rate at two years compared with those treated with CAR-T cell therapy (78.9% versus 65.6%).

Researchers also focused on outcomes in patients who had relapsed disease within the first 12 months of frontline therapy, in which auto-HCT was also associated with improved PFS (68.2% versus 48.4%) and a lower rate of relapse (25% versus 46.3%), compared with CAR T-cell therapy. Of note, the OS superiority seen in the entire cohort was not sustained with auto-HCT among those who relapsed within the first 12 months.

In the multivariable analysis, treatment with auto-HCT, when compared with CAR-T cell therapy, was associated with a lower risk of relapse/progression and of disease progression. There was no significant difference in treatment-related mortality and in OS.

The most common cause of death in the auto-HCT and CAR-T cell therapy groups was lymphoma (60% versus 68%, respectively), followed by infections (16.5% versus 12%). In the auto-HCT group, second malignancies were the third most common cause of death, occurring in 3.5% of the cohort, “as expected with high-dose chemotherapy,” Shadman said. In contrast, the third most common cause of death in patients who received CAR T-cell therapy was pulmonary failure at 8%.

CAR-T Cell Therapy Versus Auto-HCT

CAR-T cell therapy is the standard of care for relapsed LBCL and can be used as early as the second-line setting, which was determined by findings from the ZUMA-7 and TRANSFORM trials. Despite these findings, their application in clinical practice sometimes lends to a different experience.

“In practice, however, access to CAR-T (cell therapy) is not easy, and there is, most of the time, delay between the time that the decision is made to refer a patient to CAR T therapy until patients, in fact, receive treatment or even undergo leukapheresis (the removal of blood to collect certain blood cells),” Shadman said. “So many of these patients end up receiving chemotherapy while waiting for referral for the CAR T center. And some of these patients achieve a response to chemotherapy in the form of either a partial response or complete response.”

Researchers conducting this study aimed to compare outcomes of patients with LBCL who received auto-HCT with those treated with CAR T-cell therapy while in a complete response. Shadman noted that he and his team have previously shown superior efficacy of auto-HCT versus CAR T-cell therapy in patients with LBLC who were in partial remission.

The current study was an analysis of data from the Center for International Blood and Marrow Transplant Research (CIBMTR) registry of patients aged 18 to 75 years who received auto-HCT or CAR T-cell therapy while in a complete remission.

“These are patients who could at least, by age criteria, be potential candidates for (autologous) transplant even if they received CAR T,” Shadman said.

Patients were excluded if they received CAR T-cell therapy or auto-HCT previously.

The primary end points of the study were PFS and OS. Secondary endpoints included relapse/progression rate, non-relapse mortality and cause of death. Researchers also performed a subgroup analysis of patients with progressive disease 12 months after finishing first-line treatment.

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