Patient Case Study: CAR-T Cell Therapy Leads to Complete Remission for Relapsed AL Amyloidosis

AL amyloidosis is a complex disease that’s vexing to diagnose. The diagnostic journey can exceed 15 years in some cases.

In this instance, a woman in her 50s had struggled with low blood pressure, neuropathy and issues walking but no doctor had found the underlying cause. Although amyloidosis is less common in people her age, a physician in Indiana recognized the constellation of symptoms as suspicious for the disease. He referred her to Cleveland Clinic Cancer Institute.

Fast-tracking diagnosis

Cleveland Clinic has a protocol in place to accelerate the testing needed to confirm the diagnosis. As such, the team was able to swiftly arrange for testing, including mass spectrometry to identify the specific type of amyloidosis as well as a heart biopsy to assess the extent of organ involvement.

“Testing is an art, and at some centers there’s a question about whether to perform a tissue biopsy or a target organ biopsy,” explains hematologist/oncologist Shahzad Raza, MD. “But if the patient is having cardiac issues as in this case, you need to biopsy the heart.”

Within a week, the clinical team confirmed that the patient had smoldering multiple myeloma with systemic light chain (AL) amyloidosis.

Treatment course

The patient’s initial course of treatment was immunotherapy, which drives remission in roughly 60% of cases. However, she was among the subset of patients who had a suboptimal response to this therapy.

Dr. Raza was leading the first-ever human clinical trial of autologous CAR T-cell therapy called Nexicart to treat relapsed/refractory AL amyloidosis and suggested it to his patient. Aside from her heart issues she was relatively healthy, and Dr. Raza felt she would be a good candidate for the trial.

However, at the time she was struggling financially and lacked stable housing. Despite the obstacles, she was motivated and wanted to move forward with joining the research study.

Dr. Raza and his team moved quickly to ensure the patient could be successfully enrolled in the study. As soon as she was enrolled in the study, her T-cells were collected and genetically modified in a lab to target BCMA, which is frequently expressed in cancerous plasma cells. As part of a fast-track manufacturing process to avoid treatment delays, the altered cells were ready for reinfusion within two weeks.

Outcome

Within one to two weeks, the patient was in complete remission. “It’s been more than a year now and she hasn’t required any other cancer therapy,” says Dr. Raza. “When a patient goes into remission, the production of amyloidosis-causing toxins can damage the heart, liver, kidney or gut. Once you stop the source of the problem, the patient feels better and has a better quality of life.”

Once in remission, the patient’s heart performance began to improve and she regained energy levels. She has undergone several bone marrow biopsies since that time, each showing complete remission.

Key takeaways

Early study results are very encouraging. Although ongoing monitoring is needed for this patient and the 19 others in the clinical trial, researchers found the initial results very promising. “I never imagined we would have a treatment that you might be able to give one time and you’re done,” says Dr. Raza. “The deep responses we have seen are quite astonishing.”

Prompt diagnosis is essential. The American Society of Hematology has just published new guidelines for diagnosing amyloidosis. The data from this patient and others helped inform these recommendations.

Collaboration is key. “This is not a disease to be managed by hematologists alone,” says Dr. Raza. “You need a multidisciplinary approach where cardiologists and other specialists care for the patient in parallel.”