Interim Analysis Shows Exa-Cel Leads to Transfusion Independence in Beta-Thalassemia

For a large majority of patients who have transfusion-dependent β-thalassemia, myeloablation followed by exagamglogene autotemcel (exa-cel) infusion can bring transfusion independence.

This was the major finding from interim analysis of an open label phase III trial, recently published in the New England Journal of Medicine. The investigators were led by Franco Locatelli, MD, PhD, of IRCCS Bambino Gesù Children’s Research Hospital in Rome, Italy.

The study’s single group involved 52 patients with transfusion-dependent β-thalassemia, aged 12 to 35 years, and who had β0/β0, β0/β0-like, or non–β0/β0-like genotypes. These patients underwent myeloablative conditioning with busulfan and then received exa-cel. The median follow-up was 20.4 months.

For this trial, transfusion independence was the primary endpoint and the investigators defined this as a weighted average hemoglobin level of nine grams per deciliter or higher without red cell transfusion for at least 12 consecutive months.

Of the 35 patients who had sufficient follow-up data, 91% achieved transfusion independence (95% CI, 77 to 98; P<0.001 against a null hypothesis of a 50% response).

In the patients who achieved transfusion independence, the mean total hemoglobin level was 13.1 g/dL. The mean fetal hemoglobin level was 11.9 g/dL, and fetal hemoglobin also had a pancellular (at least 94% of red cells) distribution.

There were no mortalities or cancer occurrences. The investigators also found “[t]he safety profile of exa-cel was generally consistent with that of myeloablative busulfan conditioning and autologous [hematopoietic stem/progenitor cell] transplantation.”

Reference

Locatelli F, Lang P, Wall D, et al. Exagamglogene autotemcel for transfusion-dependent β-thalassemia. N Engl J Med. 2024;390(18):1663-1676. doi:10.1056/NEJMoa2309673