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ASH 2015: First-in-Human Trial Using Engineered Cells to Target Multiple Myeloma Shows Early Promise

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Key Points

  • Researchers extracted immune T cells from patients and genetically engineered the cells to express an anti–B-cell maturation antigen chimeric antigen receptor to recognize and kill myeloma cells.
  • One month following infusion, the two patients treated at the highest dose level demonstrated the strongest anticancer responses.
  • Of the six patients treated at the lowest two dose levels, one patient experienced a short partial remission of 2 weeks and the other five remained stable.

A study (Abstract LBA1) to be reported by Abbas Ali et al at the 57th American Society of Hematology (ASH) Annual Meeting demonstrated promising early outcomes of a first-in-human trial using a patient’s own genetically modified immune cells to eradicate multiple myeloma. The study findings were presented at a press conference held during the ASH meeting.

Multiple myeloma remains incurable in most cases, and new therapies are urgently needed. The B-cell maturation antigen (BCMA) is a protein expressed by both normal and malignant plasma cells. Because BCMA is only expressed by plasma cells and a small fraction of B cells, it is a promising target for the treatment of multiple myeloma.

Study Details

In this phase I clinical trial, researchers extracted immune T cells from patients and genetically engineered the cells to express an anti-BCMA chimeric antigen receptor (CAR-BCMA) to recognize and kill the myeloma cells. Patients received one round of chemotherapy before their own engineered cells were infused back into their bodies at one of four dose levels.

As of November 2015, 11 patients with advanced multiple myeloma and a median of seven previous failed therapies have participated in the trial.

Key Findings

One month following infusion, the two patients treated at the highest dose level demonstrated the strongest anticancer responses. One patient achieved a stringent complete remission at 2 months following the CAR-BCMA T-cell infusion. The other patient had undetectable myeloma in the bone marrow plasma cells but has not yet achieved complete remission status.

Of the six patients treated at the lowest two dose levels, one patient experienced a short partial remission of 2 weeks and the other five remained stable, their disease neither improving nor worsening. Two patients on the second-highest dose level maintained stable disease, and one patient obtained a very good partial response.

Toxicity and side effects were mild for patients who received the lowest dose levels. Patients who received the highest doses experienced cytokine release syndrome, a severe and potentially fatal side effect of therapy characterized by high fever, muscle pain, and heart and kidney problems.

Engineered CAR-BCMA T cells were detected in the blood of all 10 patients assessed to date. Toxicities were similar to those observed in leukemia patients treated with similar therapies.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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