ALARIC Trial Begins: First Patients Treated with CAR T-Cell Therapy for Light Chain Amyloidosis

The ALARIC trial, the first European clinical trial to evaluate CAR T-cell therapy in patients with light chain amyloidosis (AL), has treated its first three patients at University College London Hospitals (UCLH).

The trial is led by UCL and UCLH researchers, developed within the UK Myeloma Research Alliance, and supported by the National Institute for Health and Care Research (NIHR) Biomedical Research Centre. It aims to treat at least 12 patients at UCLH over two years and will also open in Leeds.

Background

Light chain amyloidosis is a rare blood disease affecting about 500 people annually in the UK. It is caused by abnormal plasma cells producing faulty light chain proteins that misfold and accumulate in organs, potentially leading to organ failure. There is no cure.

Standard treatment is chemotherapy, which involves weekly infusions for six months and maintenance therapy up to 18 months, with significant side effects. No licensed treatment exists for patients who do not respond to chemotherapy or relapse.

Trial Design and Rationale

CAR T-cell therapy involves collecting a patient's T cells, genetically modifying them to recognize and destroy abnormal plasma cells producing amyloid-forming proteins. The therapy targets B-cell maturation antigen (BCMA) present on these cells. This approach has been effective in multiple myeloma, a related blood cancer.

The ALARIC trial is a phase 1 study prioritizing safety.

Statements

Dr Lydia Lee (Principal Investigator, Consultant Haematologist at UCLH):
"For patients with relapsed or refractory AL amyloidosis, treatment options are extremely limited. CAR T-cell therapy has transformed outcomes in multiple myeloma, and this trial is an important first step in evaluating safety and efficacy in amyloidosis."

Professor Ashutosh Wechalekar (Chief Investigator):
"This phase 1 study prioritizes safety. The abnormal plasma cells in AL amyloidosis express the same target protein treated successfully in myeloma. Interrupting the disease process at its source may control the condition and improve quality of life."

Professor Allan Hackshaw (Director of CRUK & UCL Cancer Trials Centre):
"ALARIC exemplifies successful cross-sector working in non-commercial research, sponsored by UCL."

Patient Experience

Tim Wiberg, 61, of Sheffield, is the third patient treated. Diagnosed after frothy urine revealed protein in kidneys, he underwent six months of chemotherapy with partial response. He received CAR T cells on March 2 and is recovering at home.

After infusion, his lambda light chain levels dropped from about 200 to almost immeasurable.

Tags: trial, car t-cell therapy, light chain amyloidosis, clinical trial, b-cell maturation antigen