Exa-Cel Eliminates Transfusions in Patients With Thalassemia

Exagamglogene autotemcel (exa-cel) eliminated red blood cell (RBC) transfusions in patients with transfusion-dependent β-thalassemia, according to the CLIMB THAL-111 trial presented at the 2024 Tandem Transplant & Cellular Therapy Meetings of ASTCT^® and CIBMTR^®.

Exa-cel was also associated with clinically meaningful increases in fetal hemoglobin (HbF) and total hemoglobin (Hb), according to presenting author Markus Mapara, MD, of Columbia University’s Herbert Irving Comprehensive Cancer Center, and colleagues.

The study’s primary endpoint was the proportion of patients who achieved a maintained weighted average Hb ≥9.0 g/dL without red blood cell (RBC) transfusion for ≥12.0 months after exa-cel infusion, starting 60 days after the last transfusion.

A total of 44 patients (12-35 years old) with a history of RBC transfusions were included in the study. At a median of 12.3 months following exa-cel infusion, 42 of 44 (95.5%) patients discontinued RBC transfusions. The remaining two patients had 75% and 89% reductions in transfusion volume.

By three months after exa-cel infusion, patients achieved increases in HbF and Hb levels (>9.0 g/dL). The average Hb total increased to >11.0 g/dL and was subsequently maintained.

Meanwhile, the proportion of edited BCL11A alleles in bone marrow CD34-positive hematopoietic stem and progenitor cells (74.3%) and peripheral blood mononuclear cells (63.4%) remained stable in patients at six months. These data indicate successful editing of long-term hematopoietic stem cells, according to the researchers.

Two patients experienced serious adverse events related to exa-cel, such as headache, hemophagocytic lymphohistiocytosis, acute respiratory distress syndrome, idiopathic pneumonia syndrome, delayed engraftment, and thrombocytopenia.

“[The] safety profile was generally consistent with busulfan myeloablation and autologous transplant,” Dr. Mapara and colleagues concluded. “Exa-cel has the potential to be the first CRISPR/Cas9-based therapy to provide a one-time functional cure for [transfusion-dependent β-thalassemia].”

Reference

Mapara MY, Locatelli F, Lang P, et al. Transfusion independence after exagamglogene autotemcel in patients with transfusion-dependent β-thalassemia. Abstract #307. Presented at the 2024 Tandem Transplantation & Cellular Therapy Meetings of ASTCT^® and CIBMTR^®; February 21-24, 2024; San Antonio, Texas.