U.S. government researchers using a personalized therapy made from genetically engineered T cells induced remissions in some patients with highly advanced multiple myeloma, a type of blood cancer affecting plasma cells.
The encouraging results, while coming from a small trial not yet completed, lend support to a partnership between Celgene (CELG) and Bluebird Bio (BLUE) to begin testing their own version of this engineered T cell therapy in multiple myeloma patients starting next year.
In this study, presented by Dr. James Kochenderfer of the National Cancer Institute, researchers extracted immune T cells from patients, and in a lab, genetically engineered them to recognize a protein known as B-cell maturation antigen (BCMA). The BCMA protein is found on malignant and healthy plasma cells. Once injected back into the patient, the altered T cells seek out and kill BCMA-containing cells.
Engineered T cell therapies, also known as chimeric antigen receptor therapies (CAR-T), have already demonstrated high remission rates when the target is a protein known as CD19 found on leukemia and lymphoma cells. This NIH study, however, is the first time that positive responses have been seen from a CAR-T directed at the BCMA protein.
Twelve patients with heavily pre-treated multiple myeloma were enrolled in the study. Four escalating doses of the so-called CAR-BCMA therapy were infused into the patients. The overall response rate among the 12 patients was 33%.
Of the two patients receiving the highest dose, one patient achieved a complete remission at two months after infusion with the CAR-BCMA therapy. Multiple myeloma that made up 90% of this patient's bone marrow cells was eliminated by the CAR-BCMA therapy. The patient remains in complete remission 14 weeks after receiving the T cell therapy.
The other patient treated at the highest CAR-BCMA dose had undetectable myeloma in bone marrow plasma cells but had not yet reached a complete remission.
Two other patients treated with lower doses of CAR-BCMA achieved partial responses. Eight patients had stable disease.
"This is the first example of a T cell therapy that completely eradicated or decreased measurable multiple myeloma," said Korchenderfer, speaking at a media briefing Saturday morning at the American Society of Hematology (ASH) annual meeting, where the data are being presented.
Like other CAR therapies, the most severe and potentially fatal side effect seen in the CAR-BCMA therapy study was cytokine release syndrome, a type of immune system hyper-reaction which causes high fever, muscle pain, heart and kidney problems. Three patients in the study experienced cytokine release syndrome but it was managed and resolved successfully with treatment, Korchenderfer said.
Korchenderfer has a collaborative agreement with BlueBird Bio to develop a new version of this CAR-BCMA therapy. BlueBird, in turn, is working with Celgene on this therapy, known as BB2121, which starts clinical trials next year.
"We believe these [Korchenderfer] data provide excellent proof of concept for BB2121," said Rob Ross, Bluebird's head of oncology. BB2121 is Bluebird's lead oncology product.
The NIH-created CAR-BCMA therapy presented Saturday and BB2121 share the same BCMA protein target on multiple myeloma cells, but BlueBird believes BB2121 could be more potent and more persistent because it's built on the company's lentiviral vector platform. This is the same platform used in Bluebird's gene therapies for beta-thalassemia and sickle cell disease.
Bluebird has previously presented data from a mouse model of multiple myeloma showing the greater potency of BB2121. Whether that translates into better results for multiple myeloma patients will be determined by the clinical trial starting next year.
Another unresolved question from this weekend's ASH meeting presentation is where a engineered T cell therapy will ultimately fit in with other multiple myeloma treatments. In the past week, the FDA approved three new multiple myeloma drugs --competing injectable antibodies from Bristol-Myers Squibb and Johnson & Johnson, and a new oral medicine from Takeda. Celgene dominates the the commercial market in multiple myeloma with its backbone drug Revlimid.
Korchenderfer said CAR therapies in multiple myeloma are powerful but also toxic, "so they will be used after other treatments and not as front line therapy in the near future."
He added, "My goal for CAR therapies is to reduce the toxicity and get long term complete remissions," which is an outcome not seen with currently approved multiple myeloma drugs.