Autologous Hematopoietic Cell Transplantation Demonstrates Improved Outcomes Over CAR-T Among Patients With Relapsed LBCL Who Achieve Complete Remission

Among patients with relapsed large B-cell lymphoma (LBCL) who achieve a complete remission (CR), treatment with autologous hematopoietic cell transplantation (autoHCT) is associated with improved clinical outcomes compared to chimeric antigen receptor (CAR) T-cell therapy, according to results from a retrospective comparative study.

“CAR-T therapy is one of the standard-of-care options for the treatment of patients with relapsed diffuse large B-cell lymphoma (DLBCL) after at least 2 lines of therapy, and recently, axicabtagene ciloleucel (axi-cel) and lisocabtagene maraleucel (liso-cel) received the approval by the [U.S. Food and Drug Administration] to be used in second-line for patients with refractory disease or if relapsing within 12 months of first-line treatment,” stated lead study author Mazyar Shadman, MD, Fred Hutchinson Cancer Center, Seattle, Washington, and colleagues.

This retrospective observational study compared autologous hematopoietic cell transplantation (2015 to 2021) vs CAR-T (2018 to 2021) therapy using the Center for International Blood & Marrow Transplant Research (CIBMTR) registry. Eligible patients included those between ages 18 and 75 with a diagnosis of DLBCL if they received autologous hematopoietic cell transplantation (n = 281) or commercial CAR-T (n = 79) while in a CR. It was noted the median follow-up was 49.7 months for the autologous hematopoietic cell transplantation cohort and 24.7 months for the CAR-T cohort. The measured end points included progression-free survival (PFS), relapse rate, non-relapse mortality (NRM) and overall survival (OS).

Study results demonstrated that in univariate analysis, treatment with autologous hematopoietic cell transplantation was associated with a higher rate of 2-year PFS (66.2% vs 47.8%; P < 0.001), a lower 2-year cumulative incidence of relapse (27.8% vs 48%; P < 0.001), and a superior 2-year OS (78.9% vs 65.6%; P = 0.037). Furthermore, in patients with early (within 12 months) treatment failure, autologous hematopoietic cell transplantation was associated with a superior 2-year PFS (70.9% vs 48.3%; P < 0.001), lower 2-year cumulative incidence of relapse (22.8% vs 45.9%; P < 0.001) and trend for higher 2-year OS (82.4% vs 66.1%; P = 0.076). In the multivariable analysis, investigators determined treatment with autologous hematopoietic cell transplantation was associated with a greater PFS (hazard ratio [HR] 1.83; P = 0.0011) and a lower incidence of relapse (HR 2.18; P < 0.0001) compared to CAR-T.

Within the CAR-T cohort, 48 patients (68.4%) developed cytokine release syndrome (CRS) (grade 3 to 4: 2; 2.6%), and 25 patients (31.6%) developed immune effector cell-associated neurotoxicity syndrome (ICANS) (grade 3 to 4: 5; 6.3%). During the follow-up period, 85 patients (30.2%) of autologous hematopoietic cell transplantation patients and 25 patients (31.6%) of CAR-T patients died. Study authors noted the most common causes of death in both groups were first, related to disease progression [autologous hematopoietic cell transplantation patients: 51 (60%) and CAR-T: 17 (68%)] and second, to infections [autologous hematopoietic cell transplantation patients: 13 (15.3%) and CAR-T: 2 (8%)]. Additional causes of death included cardiac failure and second primary malignancies in the autologous hematopoietic cell transplantation cohort, and ICANS and second primary malignancies in the CAR-T group. COVID-19 was responsible for 1.2% and 4% of deaths in the autologous hematopoietic cell transplantation and CAR-T groups, respectively.

“In this retrospective comparative study using the CIBMTR registry, we show that the outcome of patients with relapsed LBCL who receive an [autologous hematopoietic cell transplantation] while in a CR is superior to those who receive CAR-T therapy, both in CR,” concluded Dr Shadman and colleagues.

“A discussion about the possibility of utilizing [autologous hematopoietic cell transplantation] seems reasonable and can provide a curative option for some patients while keeping CAR-T as a backup treatment plan in case of auto-HCT failure,” they added.

Source:

Shadman M, Ahn K, Kaur M, et al. Autologous transplant vs. CAR-T therapy in patients with DLBCL treated while in complete remission. Blood Cancer Journal. Published online July 8, 2024. doi: 10.1038/s41408-024-01084-w