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Stem Cell Therapy Shows Early Results with Multiple Myeloma

Multiple myeloma cells

Multiple myeloma characterized by immature plasma cells (National Library of Medicine, NIH)

1 December 2016. First results from an early clinical trial show some patients with multiple myeloma receiving replacement blood-forming stem cells achieved at least a partial response and did not suffer severe adverse effects. Findings from the clinical trial testing the treatments developed by bluebird bio — the company name is spelled in all lower-case letters — were reported today at the Molecular Targets and Cancer Therapeutics Symposium in Munich, Germany.

Multiple myeloma is a cancer of plasma cells, white blood cells helping fight infections by making antibodies that recognize invading pathogens. The disorder causes cancerous cells to accumulate in the bone marrow, crowding out healthy plasma cells. Instead of antibodies, the malfunctioning cancer cells produce abnormal myeloma proteins that cause kidney problems and other disorders. American Cancer Society expects more than 30,000 new cases of multiple myeloma to occur in the U.S. this year, causing almost 12,700 deaths.

bluebird bio develops treatments for severe genetic and rare diseases with a technology based in part on the work of co-founder Philippe Leboulch, a researcher and lecturer at Paris University School of Medicine, Harvard Medical School, MIT, and Brigham and Women’s Hospital in Boston. Leboulch serves as a scientific advisor to bluebird bio.

The company’s cancer technology takes a patient’s own hematopoietic (bone marrow) stem cells and cultures them outside the body using healthy genes delivered with benign viruses called lentiviruses. The culturing process creates replacement genes for the mutated stem cells causing the disease.

The replacement genes modify the chimeric antigen receptors or CARs on the individual’s T-cells, key white blood cells in the immune system. These CAR T-cells then bind to targeted proteins on the surface of cancer cells and destroy them. In this case, the CAR T-cells aim for B cell maturation antigens, considered a promising target for multiple myeloma.

The clinical trial is testing the safety of the company’s lead cancer treatment code-named bb2121 that uses CAR-T technology at 3 dosage levels, after pretreatments with the chemotherapy drugs cyclophosphamide and fludarabine. While the study is looking primarily for adverse effects from the treatments, particularly those that may limit the dosage, the research team is evaluating clinical outcomes as well. The trial aims to eventually enroll 50 participants with stubborn or relapsing multiple myeloma at 7 sites in the U.S., but results reported today covered the first 9 individuals treated by the end of October, with 3 individuals each receiving a low, medium, or high dose of bb2121.

At the medium and higher dose levels, all 6 participants reported at least a partial response — 50 percent or more reduction in myeloma proteins — or stable disease state, indicating no further disease progression, from 4 to 28 weeks following the treatment. One individual achieved a very good partial response, indicating a 90 percent decrease of myeloma proteins in the blood, which correlates with longer event-free and overall survival. Two participants reported stringent complete responses, meaning no sign myeloma proteins in the blood or plasma cells in bone marrow.

Among the three lower dose recipients, one continued with a progressive form of the disease, while the second individual achieved a stable disease state, and the third reported a partial response.

The most common adverse effect was cytokine release syndrome that occurs when enzymes are emitted from cells targeted by treatments, which can cause flu-like symptoms such as fevers, nausea, and muscle pain, as well as neurological symptoms including hallucinations and delirium. About two-thirds of the participants reported mild to moderate cytokine release syndrome. Other mild to moderate adverse effects were low while blood cell counts and anemia. No severe adverse effects, nor any toxicities that would require dose limitations, were reported.

Adverse effects with CAR-T therapies are receiving more scrutiny recently following the second stoppage of a clinical trial testing a similar CAR-T treatments on patients with acute lymphoblastic leukemia. As reported in Science & Enterprise, those patients were also first treated with cyclophosphamide or fludarabine.

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